Kerri Wachter

WASHINGTON — Physicians and patients need to work together to decide for or against long-term bisphosphonate treatment for osteoporosis, said Dr. Sundeep Khosla at an international symposium sponsored by the National Osteoporosis Foundation

Alendronate is the longest-available bisphosphonate, with 10 years of follow-up data. In one analysis of 10 years of data for postmenopausal women on varying regimens of alendronate, those on 10 mg daily of alendronate had increased BMD for the spine and hip (N. Engl. J. Med. 2004;350:1189–99). Spine BMD increased by 14% from baseline over that period, and total hip BMD increased by 7%.

Smaller gains in BMD were noted for women on 5 mg daily of alendronate: 9% and 3% for the spine and total hip, respectively.

For women in the discontinuation group, spinal BMD leveled off (an increase of 0.3% from years 6–10) and total hip BMD declined slightly (a decrease of 1% from years 6–10).

This study “told us that alendronate did in fact have sustained effects over 10 years on bone density and bone turnover markers,” said Dr. Khosla, research chair of the division of endocrinology at the Mayo Clinic in Rochester, Minn. However, the fracture data were inconclusive.

In the FLEX (Fracture Intervention Trial [FIT] Long-Term Extension) study, published late last year, researchers assessed the effects of continuing or stopping alendronate after 5 years of treatment (JAMA 2006;296:2927–38).

For women on placebo for years 5–10, total hip BMD returned to baseline levels. Women on 5 mg/day or 10 mg/day of alendronate gained and maintained a 4% increase in hip BMD over baseline during the same period.

Women on placebo during years 5–10 had a slight increase in spine BMD, and women on alendronate had a steeper increase. Women who continued on alendronate for 10 years had an almost 50% reduction in clinical vertebral fractures, compared with those who stopped treatment after 5 years. There was no difference between the groups in terms of nonvertebral or morphometric vertebral fractures.

“Continuation of alendronate for 10 years maintains bone mass and reduces bone remodeling, compared with discontinuation after 5 years,” said Dr. Khosla.

Discontinuation did not increase the risk of nonvertebral fractures or x-ray-detected vertebral fractures, but the risk of clinically detected vertebral fractures was significantly increased in those who discontinued therapy after 5 years.

“For many women, stopping alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of vertebral fractures—such as those who already have a vertebral fracture or those [who might have] very low bone density—may benefit by continuing beyond 5 years.”

WASHINGTON — Physicians and patients need to work together to decide for or against long-term bisphosphonate treatment for osteoporosis, said Dr. Sundeep Khosla at an international symposium sponsored by the National Osteoporosis Foundation

Alendronate is the longest-available bisphosphonate, with 10 years of follow-up data. In one analysis of 10 years of data for postmenopausal women on varying regimens of alendronate, those on 10 mg daily of alendronate had increased BMD for the spine and hip (N. Engl. J. Med. 2004;350:1189–99). Spine BMD increased by 14% from baseline over that period, and total hip BMD increased by 7%.

Smaller gains in BMD were noted for women on 5 mg daily of alendronate: 9% and 3% for the spine and total hip, respectively.

For women in the discontinuation group, spinal BMD leveled off (an increase of 0.3% from years 6–10) and total hip BMD declined slightly (a decrease of 1% from years 6–10).

This study “told us that alendronate did in fact have sustained effects over 10 years on bone density and bone turnover markers,” said Dr. Khosla, research chair of the division of endocrinology at the Mayo Clinic in Rochester, Minn. However, the fracture data were inconclusive.

In the FLEX (Fracture Intervention Trial [FIT] Long-Term Extension) study, published late last year, researchers assessed the effects of continuing or stopping alendronate after 5 years of treatment (JAMA 2006;296:2927–38).

For women on placebo for years 5–10, total hip BMD returned to baseline levels. Women on 5 mg/day or 10 mg/day of alendronate gained and maintained a 4% increase in hip BMD over baseline during the same period.

Women on placebo during years 5–10 had a slight increase in spine BMD, and women on alendronate had a steeper increase. Women who continued on alendronate for 10 years had an almost 50% reduction in clinical vertebral fractures, compared with those who stopped treatment after 5 years. There was no difference between the groups in terms of nonvertebral or morphometric vertebral fractures.

“Continuation of alendronate for 10 years maintains bone mass and reduces bone remodeling, compared with discontinuation after 5 years,” said Dr. Khosla.

Discontinuation did not increase the risk of nonvertebral fractures or x-ray-detected vertebral fractures, but the risk of clinically detected vertebral fractures was significantly increased in those who discontinued therapy after 5 years.

“For many women, stopping alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of vertebral fractures—such as those who already have a vertebral fracture or those [who might have] very low bone density—may benefit by continuing beyond 5 years.”

WASHINGTON — Physicians and patients need to work together to decide for or against long-term bisphosphonate treatment for osteoporosis, said Dr. Sundeep Khosla at an international symposium sponsored by the National Osteoporosis Foundation

Alendronate is the longest-available bisphosphonate, with 10 years of follow-up data. In one analysis of 10 years of data for postmenopausal women on varying regimens of alendronate, those on 10 mg daily of alendronate had increased BMD for the spine and hip (N. Engl. J. Med. 2004;350:1189–99). Spine BMD increased by 14% from baseline over that period, and total hip BMD increased by 7%.

Smaller gains in BMD were noted for women on 5 mg daily of alendronate: 9% and 3% for the spine and total hip, respectively.

For women in the discontinuation group, spinal BMD leveled off (an increase of 0.3% from years 6–10) and total hip BMD declined slightly (a decrease of 1% from years 6–10).

This study “told us that alendronate did in fact have sustained effects over 10 years on bone density and bone turnover markers,” said Dr. Khosla, research chair of the division of endocrinology at the Mayo Clinic in Rochester, Minn. However, the fracture data were inconclusive.

In the FLEX (Fracture Intervention Trial [FIT] Long-Term Extension) study, published late last year, researchers assessed the effects of continuing or stopping alendronate after 5 years of treatment (JAMA 2006;296:2927–38).

For women on placebo for years 5–10, total hip BMD returned to baseline levels. Women on 5 mg/day or 10 mg/day of alendronate gained and maintained a 4% increase in hip BMD over baseline during the same period.

Women on placebo during years 5–10 had a slight increase in spine BMD, and women on alendronate had a steeper increase. Women who continued on alendronate for 10 years had an almost 50% reduction in clinical vertebral fractures, compared with those who stopped treatment after 5 years. There was no difference between the groups in terms of nonvertebral or morphometric vertebral fractures.

“Continuation of alendronate for 10 years maintains bone mass and reduces bone remodeling, compared with discontinuation after 5 years,” said Dr. Khosla.

Discontinuation did not increase the risk of nonvertebral fractures or x-ray-detected vertebral fractures, but the risk of clinically detected vertebral fractures was significantly increased in those who discontinued therapy after 5 years.

“For many women, stopping alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of vertebral fractures—such as those who already have a vertebral fracture or those [who might have] very low bone density—may benefit by continuing beyond 5 years.”

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

Conventional MRI has helped characterize the variety of neuropsychiatric systemic lupus erythematosus symptoms, including atrophy, focal or diffuse nonspecific white matter lesions, hemorrhage, infarcts, and demyelination. However, conventional MRI may be negative or nonspecific, even in symptomatic patients.

MR spectroscopy has found protein ratios that may represent inflammatory processes, demyelination, or cell membrane degradation, all of which involve microstructural changes that affect how water molecules move—the diffusivity.

Diffusion-weighted imaging (DWI), an MR-based technique, is sensitive to water's motion within extracellular space. DWI can diagnose and characterize abnormalities in brain tissue.

Diffusion tensor imaging (DTI) analyzes the directional diffusion properties of water and the integrity of organized tissue microstructures. It is often applied to white matter tracts to reveal tissue orientation and integrity.

Tractography lets researchers see the symmetry of brain water diffusion. Bundles of fiber tracts make the water diffuse asymmetrically in the major axis parallel to the direction of the fibers. The asymmetry is called anisotropy. A direct relationship exists between the number of fibers and the degree of anisotropy.

Aziz M. Ulug, Ph.D., of Cornell University, Ithaca, N. Y., and colleagues used these techniques to study 34 SLE patients and 29 age-matched controls. Participants underwent MRI (1.5 T), DWI, DTI, and tractography (Magn. Reson. Imaging 2007;25:399–405). Overall, 20 patients had an abnormal MRI finding: 3 showed volume loss inappropriate for age; 15 had focal or spreading nonspecific white matter disease; and 2 showed both volume loss and nonspecific white matter disease.

The Dav is average diffusion constant for all MRI pixels. The greater Dav, the more freely water diffuses. In SLE, there were regions where Dav was higher, versus controls. In the entire SLE group, Dav was higher in the anterior internal capsule, frontal lobe, and splenium of corpus callosum.

BDav is the diffusion constant (Dav) measured from the entire brain. BDav is is useful for diseases in which the insult is not focal or not exactly known. “In SLE patients, we find BDav is increased compared to normals,” said Dr. Ulug. “The disease [is] affecting a large portion of the brain (or entire brain). The BDav value was increased in the patient group that [had] normal MRI findings, compared with controls. This means the BDav measure is a very sensitive one that detects the disease or disease load in the brain before regular MRI.”

Diffusion anisotropy in the anterior internal capsule was significantly decreased in the patient group, suggesting a preclinical impairment of axon integrity (contained in the anterior internal capsule and running to and from the frontal association cortex). Anisotropy in the anterior internal capsule for patients with normal MRI findings was lower than in patients with abnormal MRI findings. This suggests ractional anisotropy is a sensitive tool to detect early signs of disease involvement. Tractography in SLE patients showed fewer trackable fibers in the whole brain compared with controls, suggesting white matter damage, said Dr. Ulug.

Patients with SLE (left) have fewer trackable white matter fibers within the whole brain, compared with healthy controls (right), on DTI tractography. Images courtesy Aziz M. Ulug, Ph.D.

Conventional MRI has helped characterize the variety of neuropsychiatric systemic lupus erythematosus symptoms, including atrophy, focal or diffuse nonspecific white matter lesions, hemorrhage, infarcts, and demyelination. However, conventional MRI may be negative or nonspecific, even in symptomatic patients.

MR spectroscopy has found protein ratios that may represent inflammatory processes, demyelination, or cell membrane degradation, all of which involve microstructural changes that affect how water molecules move—the diffusivity.

Diffusion-weighted imaging (DWI), an MR-based technique, is sensitive to water's motion within extracellular space. DWI can diagnose and characterize abnormalities in brain tissue.

Diffusion tensor imaging (DTI) analyzes the directional diffusion properties of water and the integrity of organized tissue microstructures. It is often applied to white matter tracts to reveal tissue orientation and integrity.

Tractography lets researchers see the symmetry of brain water diffusion. Bundles of fiber tracts make the water diffuse asymmetrically in the major axis parallel to the direction of the fibers. The asymmetry is called anisotropy. A direct relationship exists between the number of fibers and the degree of anisotropy.

Aziz M. Ulug, Ph.D., of Cornell University, Ithaca, N. Y., and colleagues used these techniques to study 34 SLE patients and 29 age-matched controls. Participants underwent MRI (1.5 T), DWI, DTI, and tractography (Magn. Reson. Imaging 2007;25:399–405). Overall, 20 patients had an abnormal MRI finding: 3 showed volume loss inappropriate for age; 15 had focal or spreading nonspecific white matter disease; and 2 showed both volume loss and nonspecific white matter disease.

The Dav is average diffusion constant for all MRI pixels. The greater Dav, the more freely water diffuses. In SLE, there were regions where Dav was higher, versus controls. In the entire SLE group, Dav was higher in the anterior internal capsule, frontal lobe, and splenium of corpus callosum.

BDav is the diffusion constant (Dav) measured from the entire brain. BDav is is useful for diseases in which the insult is not focal or not exactly known. “In SLE patients, we find BDav is increased compared to normals,” said Dr. Ulug. “The disease [is] affecting a large portion of the brain (or entire brain). The BDav value was increased in the patient group that [had] normal MRI findings, compared with controls. This means the BDav measure is a very sensitive one that detects the disease or disease load in the brain before regular MRI.”

Diffusion anisotropy in the anterior internal capsule was significantly decreased in the patient group, suggesting a preclinical impairment of axon integrity (contained in the anterior internal capsule and running to and from the frontal association cortex). Anisotropy in the anterior internal capsule for patients with normal MRI findings was lower than in patients with abnormal MRI findings. This suggests ractional anisotropy is a sensitive tool to detect early signs of disease involvement. Tractography in SLE patients showed fewer trackable fibers in the whole brain compared with controls, suggesting white matter damage, said Dr. Ulug.

Patients with SLE (left) have fewer trackable white matter fibers within the whole brain, compared with healthy controls (right), on DTI tractography. Images courtesy Aziz M. Ulug, Ph.D.

Conventional MRI has helped characterize the variety of neuropsychiatric systemic lupus erythematosus symptoms, including atrophy, focal or diffuse nonspecific white matter lesions, hemorrhage, infarcts, and demyelination. However, conventional MRI may be negative or nonspecific, even in symptomatic patients.

MR spectroscopy has found protein ratios that may represent inflammatory processes, demyelination, or cell membrane degradation, all of which involve microstructural changes that affect how water molecules move—the diffusivity.

Diffusion-weighted imaging (DWI), an MR-based technique, is sensitive to water's motion within extracellular space. DWI can diagnose and characterize abnormalities in brain tissue.

Diffusion tensor imaging (DTI) analyzes the directional diffusion properties of water and the integrity of organized tissue microstructures. It is often applied to white matter tracts to reveal tissue orientation and integrity.

Tractography lets researchers see the symmetry of brain water diffusion. Bundles of fiber tracts make the water diffuse asymmetrically in the major axis parallel to the direction of the fibers. The asymmetry is called anisotropy. A direct relationship exists between the number of fibers and the degree of anisotropy.

Aziz M. Ulug, Ph.D., of Cornell University, Ithaca, N. Y., and colleagues used these techniques to study 34 SLE patients and 29 age-matched controls. Participants underwent MRI (1.5 T), DWI, DTI, and tractography (Magn. Reson. Imaging 2007;25:399–405). Overall, 20 patients had an abnormal MRI finding: 3 showed volume loss inappropriate for age; 15 had focal or spreading nonspecific white matter disease; and 2 showed both volume loss and nonspecific white matter disease.

The Dav is average diffusion constant for all MRI pixels. The greater Dav, the more freely water diffuses. In SLE, there were regions where Dav was higher, versus controls. In the entire SLE group, Dav was higher in the anterior internal capsule, frontal lobe, and splenium of corpus callosum.

BDav is the diffusion constant (Dav) measured from the entire brain. BDav is is useful for diseases in which the insult is not focal or not exactly known. “In SLE patients, we find BDav is increased compared to normals,” said Dr. Ulug. “The disease [is] affecting a large portion of the brain (or entire brain). The BDav value was increased in the patient group that [had] normal MRI findings, compared with controls. This means the BDav measure is a very sensitive one that detects the disease or disease load in the brain before regular MRI.”

Diffusion anisotropy in the anterior internal capsule was significantly decreased in the patient group, suggesting a preclinical impairment of axon integrity (contained in the anterior internal capsule and running to and from the frontal association cortex). Anisotropy in the anterior internal capsule for patients with normal MRI findings was lower than in patients with abnormal MRI findings. This suggests ractional anisotropy is a sensitive tool to detect early signs of disease involvement. Tractography in SLE patients showed fewer trackable fibers in the whole brain compared with controls, suggesting white matter damage, said Dr. Ulug.

Patients with SLE (left) have fewer trackable white matter fibers within the whole brain, compared with healthy controls (right), on DTI tractography. Images courtesy Aziz M. Ulug, Ph.D.

WASHINGTON — In a multicenter study, capsule endoscopy showed promise in the detection of significant colorectal polyps, and the technique may someday offer a noninvasive alternative to conventional colonoscopy, Dr. Jacques Devière said at the annual Digestive Disease Week.

For significant lesions—those greater than 6 mm in size—or in patients with three or more polyps, the sensitivity of capsule endoscopy using the PillCam COLON was 79% and specificity was 78%, compared with conventional colonoscopy. The positive predictive value (PPV) was 75%, and the negative predictive value (NPV) was 82%, Dr. Devière reported.

A total of 275 polyps were identified with the PillCam. For polyps of any size, the PillCam had a sensitivity and specificity of 76%. PPV was 88% and NPV was 58%.

If validated, “this noninvasive technology might challenge colonoscopy for colon cancer screening and polyp detection in the future,” said Dr. Devière, a gastroenterologist at the Hôpital Erasme in Brussels.

The study was sponsored by Given Imaging Ltd., maker of the PillCam COLON. Dr. Devière disclosed that he has received research support from the company.

A total of 84 patients at eight centers were included; 64% were male, and the average age was 60 years. Patients were included if they had an adenoma and were asked to come back for surveillance after 3 years, or if they were suspected of having colonic disease and were referred for conventional colonoscopy. Patients were excluded if they had Crohn's disease, small bowel tumors, radiation enteritis, or surgical anastomoses.

On the day before the procedure, patients were limited to a clear liquid diet. In the evening, they drank 4 L of polyethylene glycol preparation (Colopeg).

At 7 a.m. the next day, patients drank another liter of Colopeg, followed by 20 mg of domperidone (to aid excretion of the capsule). They swallowed the capsule an hour later. At 10 a.m., patients drank a “booster” of 45 mL sodium phosphate.

Using this regimen, 77% of patients excreted the capsule by 2 p.m. The remaining patients required a second booster of 30 mL sodium phosphate. Patients were allowed a low-fiber snack at 3 p.m. If the capsule had not been excreted by 4:30 p.m., patients received 10 mg bisacodyl.

Conventional colonoscopy was performed in all patients after the capsule was excreted that day in order to allow comparisons to be made between the two methods.

Colon preparation was rated as poor, fair, good, or excellent. Preparation was considered poor if there was a large amount of fecal residue that impaired visualization, fair if there were enough areas of evacuation to allow a reliable examination, good if there was only a small amount of residue, and excellent if no or very small amounts of residue were present.

Most patients (57%) had a good preparation, followed by 29% with a fair prep, 9% with an excellent prep, and 5% with a poor prep. “There is still some problem with the quality of the preparation,” Dr. Devière said.

By the end of the battery life (10 hours), 92% of the capsules had been excreted and 4% were still in the sigmoid colon; two capsules were never eliminated from the stomach because the patients had gastroparesis. In these two patients, additional endoscopies had to be performed to push the capsules out of the stomach.

The capsule measures 11 mm by 31 mm—roughly the size of a large vitamin pill—and it has tiny cameras that capture four images per second. The capsule has a sleep mode of 2 hours to preserve the battery between the time it is swallowed and the approximate time it enters the colon.

WASHINGTON — In a multicenter study, capsule endoscopy showed promise in the detection of significant colorectal polyps, and the technique may someday offer a noninvasive alternative to conventional colonoscopy, Dr. Jacques Devière said at the annual Digestive Disease Week.

For significant lesions—those greater than 6 mm in size—or in patients with three or more polyps, the sensitivity of capsule endoscopy using the PillCam COLON was 79% and specificity was 78%, compared with conventional colonoscopy. The positive predictive value (PPV) was 75%, and the negative predictive value (NPV) was 82%, Dr. Devière reported.

A total of 275 polyps were identified with the PillCam. For polyps of any size, the PillCam had a sensitivity and specificity of 76%. PPV was 88% and NPV was 58%.

If validated, “this noninvasive technology might challenge colonoscopy for colon cancer screening and polyp detection in the future,” said Dr. Devière, a gastroenterologist at the Hôpital Erasme in Brussels.

The study was sponsored by Given Imaging Ltd., maker of the PillCam COLON. Dr. Devière disclosed that he has received research support from the company.

A total of 84 patients at eight centers were included; 64% were male, and the average age was 60 years. Patients were included if they had an adenoma and were asked to come back for surveillance after 3 years, or if they were suspected of having colonic disease and were referred for conventional colonoscopy. Patients were excluded if they had Crohn's disease, small bowel tumors, radiation enteritis, or surgical anastomoses.

On the day before the procedure, patients were limited to a clear liquid diet. In the evening, they drank 4 L of polyethylene glycol preparation (Colopeg).

At 7 a.m. the next day, patients drank another liter of Colopeg, followed by 20 mg of domperidone (to aid excretion of the capsule). They swallowed the capsule an hour later. At 10 a.m., patients drank a “booster” of 45 mL sodium phosphate.

Using this regimen, 77% of patients excreted the capsule by 2 p.m. The remaining patients required a second booster of 30 mL sodium phosphate. Patients were allowed a low-fiber snack at 3 p.m. If the capsule had not been excreted by 4:30 p.m., patients received 10 mg bisacodyl.

Conventional colonoscopy was performed in all patients after the capsule was excreted that day in order to allow comparisons to be made between the two methods.

Colon preparation was rated as poor, fair, good, or excellent. Preparation was considered poor if there was a large amount of fecal residue that impaired visualization, fair if there were enough areas of evacuation to allow a reliable examination, good if there was only a small amount of residue, and excellent if no or very small amounts of residue were present.

Most patients (57%) had a good preparation, followed by 29% with a fair prep, 9% with an excellent prep, and 5% with a poor prep. “There is still some problem with the quality of the preparation,” Dr. Devière said.

By the end of the battery life (10 hours), 92% of the capsules had been excreted and 4% were still in the sigmoid colon; two capsules were never eliminated from the stomach because the patients had gastroparesis. In these two patients, additional endoscopies had to be performed to push the capsules out of the stomach.

The capsule measures 11 mm by 31 mm—roughly the size of a large vitamin pill—and it has tiny cameras that capture four images per second. The capsule has a sleep mode of 2 hours to preserve the battery between the time it is swallowed and the approximate time it enters the colon.

WASHINGTON — In a multicenter study, capsule endoscopy showed promise in the detection of significant colorectal polyps, and the technique may someday offer a noninvasive alternative to conventional colonoscopy, Dr. Jacques Devière said at the annual Digestive Disease Week.

For significant lesions—those greater than 6 mm in size—or in patients with three or more polyps, the sensitivity of capsule endoscopy using the PillCam COLON was 79% and specificity was 78%, compared with conventional colonoscopy. The positive predictive value (PPV) was 75%, and the negative predictive value (NPV) was 82%, Dr. Devière reported.

A total of 275 polyps were identified with the PillCam. For polyps of any size, the PillCam had a sensitivity and specificity of 76%. PPV was 88% and NPV was 58%.

If validated, “this noninvasive technology might challenge colonoscopy for colon cancer screening and polyp detection in the future,” said Dr. Devière, a gastroenterologist at the Hôpital Erasme in Brussels.

The study was sponsored by Given Imaging Ltd., maker of the PillCam COLON. Dr. Devière disclosed that he has received research support from the company.

A total of 84 patients at eight centers were included; 64% were male, and the average age was 60 years. Patients were included if they had an adenoma and were asked to come back for surveillance after 3 years, or if they were suspected of having colonic disease and were referred for conventional colonoscopy. Patients were excluded if they had Crohn's disease, small bowel tumors, radiation enteritis, or surgical anastomoses.

On the day before the procedure, patients were limited to a clear liquid diet. In the evening, they drank 4 L of polyethylene glycol preparation (Colopeg).

At 7 a.m. the next day, patients drank another liter of Colopeg, followed by 20 mg of domperidone (to aid excretion of the capsule). They swallowed the capsule an hour later. At 10 a.m., patients drank a “booster” of 45 mL sodium phosphate.

Using this regimen, 77% of patients excreted the capsule by 2 p.m. The remaining patients required a second booster of 30 mL sodium phosphate. Patients were allowed a low-fiber snack at 3 p.m. If the capsule had not been excreted by 4:30 p.m., patients received 10 mg bisacodyl.

Conventional colonoscopy was performed in all patients after the capsule was excreted that day in order to allow comparisons to be made between the two methods.

Colon preparation was rated as poor, fair, good, or excellent. Preparation was considered poor if there was a large amount of fecal residue that impaired visualization, fair if there were enough areas of evacuation to allow a reliable examination, good if there was only a small amount of residue, and excellent if no or very small amounts of residue were present.

Most patients (57%) had a good preparation, followed by 29% with a fair prep, 9% with an excellent prep, and 5% with a poor prep. “There is still some problem with the quality of the preparation,” Dr. Devière said.

By the end of the battery life (10 hours), 92% of the capsules had been excreted and 4% were still in the sigmoid colon; two capsules were never eliminated from the stomach because the patients had gastroparesis. In these two patients, additional endoscopies had to be performed to push the capsules out of the stomach.

The capsule measures 11 mm by 31 mm—roughly the size of a large vitamin pill—and it has tiny cameras that capture four images per second. The capsule has a sleep mode of 2 hours to preserve the battery between the time it is swallowed and the approximate time it enters the colon.

WASHINGTON — Physicians don't seem to be doing such a good job of adhering to recommendations for colonoscopy surveillance, following some patients too often and not following others often enough, Dr. Robert E. Schoen reported at the annual Digestive Disease Week.

Dr. Schoen, a professor of medicine and epidemiology at the University of Pittsburgh, and his colleagues looked at surveillance colonoscopy records for 3,607 participants (60% men, 93% white) in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. All of the patients had an abnormal screening flexible sigmoidoscopy and then underwent diagnostic colonoscopy within 1 year.

At 5 years' follow-up, only 63% of the patients with advanced adenoma had undergone a surveillance colonoscopy. At 10 years, 83% had had a follow-up colonoscopy. On the other side of the spectrum, 40% of those with no polyps had undergone a surveillance colonoscopy at 5 years; that number rose to 64% at 10 years. (See box.)

“There is an element of both underutilization and overutilization,” Dr. Schoen said. According to recommendations by the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society, patients with two or fewer small (less than 1-cm) tubular adenomas with only low-grade dysplasia should have their next follow-up colonoscopy in 5–10 years. Patients with small rectal hyperplastic polyps should be considered to have normal colonoscopies and should have their next follow-up colonoscopy in 10 years. Patients with 3–10 adenomas, any adenoma 1 cm or larger, any adenoma with villous features, or high-grade dysplasia should have a follow-up colonoscopy in 3 years (Gastroenterology 2006;130:1872–85.)

In the PLCO trial, patients who had an abnormal flexible sigmoidoscopy were referred to their primary care physician for a decision regarding further testing. Colonoscopies were performed by community-based physicians, not trial investigators. Likewise, surveillance decisions were made by community-based physicians.

For this study, patients were interviewed over the telephone. They were reminded of their baseline colonoscopy findings and asked about follow-up surveillance colonoscopy. Medical records were used to confirm reported colonoscopies. There were at least 5 years of follow-up data after the baseline colonoscopy, with a median of 9 years.

At baseline colonoscopy, 37% of the patients had advanced adenoma, 28% had a nonadvanced adenoma, 20% had hyperplastic polyps or another benign mucosal abnormality, and 15% had no polyps.

At 7 years, 34% of those with advanced adenoma, 20% of those with nonadvanced adenoma, 15% of those with benign polyps or abnormalities, and 15% of those with no polyps had at least two follow-up colonoscopies.

Patients aged 70–74 with an advanced adenoma had an odds ratio of 1.6 for not getting a follow-up colonoscopy, compared with younger patients with an advanced adenoma.

Participants in the PLCO trial were recruited through 10 regional centers across the United States. Individuals were asymptomatic upon enrollment. The study involved 154,942 people aged 55–74 years at entry, and more than 65,000 individuals had a flexible sigmoidoscopy.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Physicians don't seem to be doing such a good job of adhering to recommendations for colonoscopy surveillance, following some patients too often and not following others often enough, Dr. Robert E. Schoen reported at the annual Digestive Disease Week.

Dr. Schoen, a professor of medicine and epidemiology at the University of Pittsburgh, and his colleagues looked at surveillance colonoscopy records for 3,607 participants (60% men, 93% white) in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. All of the patients had an abnormal screening flexible sigmoidoscopy and then underwent diagnostic colonoscopy within 1 year.

At 5 years' follow-up, only 63% of the patients with advanced adenoma had undergone a surveillance colonoscopy. At 10 years, 83% had had a follow-up colonoscopy. On the other side of the spectrum, 40% of those with no polyps had undergone a surveillance colonoscopy at 5 years; that number rose to 64% at 10 years. (See box.)

“There is an element of both underutilization and overutilization,” Dr. Schoen said. According to recommendations by the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society, patients with two or fewer small (less than 1-cm) tubular adenomas with only low-grade dysplasia should have their next follow-up colonoscopy in 5–10 years. Patients with small rectal hyperplastic polyps should be considered to have normal colonoscopies and should have their next follow-up colonoscopy in 10 years. Patients with 3–10 adenomas, any adenoma 1 cm or larger, any adenoma with villous features, or high-grade dysplasia should have a follow-up colonoscopy in 3 years (Gastroenterology 2006;130:1872–85.)

In the PLCO trial, patients who had an abnormal flexible sigmoidoscopy were referred to their primary care physician for a decision regarding further testing. Colonoscopies were performed by community-based physicians, not trial investigators. Likewise, surveillance decisions were made by community-based physicians.

For this study, patients were interviewed over the telephone. They were reminded of their baseline colonoscopy findings and asked about follow-up surveillance colonoscopy. Medical records were used to confirm reported colonoscopies. There were at least 5 years of follow-up data after the baseline colonoscopy, with a median of 9 years.

At baseline colonoscopy, 37% of the patients had advanced adenoma, 28% had a nonadvanced adenoma, 20% had hyperplastic polyps or another benign mucosal abnormality, and 15% had no polyps.

At 7 years, 34% of those with advanced adenoma, 20% of those with nonadvanced adenoma, 15% of those with benign polyps or abnormalities, and 15% of those with no polyps had at least two follow-up colonoscopies.

Patients aged 70–74 with an advanced adenoma had an odds ratio of 1.6 for not getting a follow-up colonoscopy, compared with younger patients with an advanced adenoma.

Participants in the PLCO trial were recruited through 10 regional centers across the United States. Individuals were asymptomatic upon enrollment. The study involved 154,942 people aged 55–74 years at entry, and more than 65,000 individuals had a flexible sigmoidoscopy.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Physicians don't seem to be doing such a good job of adhering to recommendations for colonoscopy surveillance, following some patients too often and not following others often enough, Dr. Robert E. Schoen reported at the annual Digestive Disease Week.

Dr. Schoen, a professor of medicine and epidemiology at the University of Pittsburgh, and his colleagues looked at surveillance colonoscopy records for 3,607 participants (60% men, 93% white) in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. All of the patients had an abnormal screening flexible sigmoidoscopy and then underwent diagnostic colonoscopy within 1 year.

At 5 years' follow-up, only 63% of the patients with advanced adenoma had undergone a surveillance colonoscopy. At 10 years, 83% had had a follow-up colonoscopy. On the other side of the spectrum, 40% of those with no polyps had undergone a surveillance colonoscopy at 5 years; that number rose to 64% at 10 years. (See box.)

“There is an element of both underutilization and overutilization,” Dr. Schoen said. According to recommendations by the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society, patients with two or fewer small (less than 1-cm) tubular adenomas with only low-grade dysplasia should have their next follow-up colonoscopy in 5–10 years. Patients with small rectal hyperplastic polyps should be considered to have normal colonoscopies and should have their next follow-up colonoscopy in 10 years. Patients with 3–10 adenomas, any adenoma 1 cm or larger, any adenoma with villous features, or high-grade dysplasia should have a follow-up colonoscopy in 3 years (Gastroenterology 2006;130:1872–85.)

In the PLCO trial, patients who had an abnormal flexible sigmoidoscopy were referred to their primary care physician for a decision regarding further testing. Colonoscopies were performed by community-based physicians, not trial investigators. Likewise, surveillance decisions were made by community-based physicians.

For this study, patients were interviewed over the telephone. They were reminded of their baseline colonoscopy findings and asked about follow-up surveillance colonoscopy. Medical records were used to confirm reported colonoscopies. There were at least 5 years of follow-up data after the baseline colonoscopy, with a median of 9 years.

At baseline colonoscopy, 37% of the patients had advanced adenoma, 28% had a nonadvanced adenoma, 20% had hyperplastic polyps or another benign mucosal abnormality, and 15% had no polyps.

At 7 years, 34% of those with advanced adenoma, 20% of those with nonadvanced adenoma, 15% of those with benign polyps or abnormalities, and 15% of those with no polyps had at least two follow-up colonoscopies.

Patients aged 70–74 with an advanced adenoma had an odds ratio of 1.6 for not getting a follow-up colonoscopy, compared with younger patients with an advanced adenoma.

Participants in the PLCO trial were recruited through 10 regional centers across the United States. Individuals were asymptomatic upon enrollment. The study involved 154,942 people aged 55–74 years at entry, and more than 65,000 individuals had a flexible sigmoidoscopy.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — With billions of dollars at stake and the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are emerging all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For the oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). And the answer depends on whom you ask, judging from four poster presentations.

Two studies involving researchers from Roche Laboratories Inc. (codeveloper of Boniva, along with GlaxoSmithKline) suggested that not only did women prefer once-monthly ibandronate but they were also more likely to persist with the drug than were those on once-weekly alendronate or risedronate.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and his colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate.

The unadjusted 9-month persistence rates were 41% for patients receiving monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy.

Monthly ibandronate users were 31% more likely to be persistent with therapy, compared with those on weekly alendronate or risedronate, after controlling for age, copay, comorbidities, and prescriptions greater than a 30-day supply. “After accounting for potential confounding factors, the increased likelihood of persistence reflects the independent effect of dosing frequency on patient persistence,” the researchers wrote.

In the second study, postmenopausal women were enrolled in a prospective, open-label study if they had been receiving once-weekly alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for a minimum of 3 months. The women were given once-monthly ibandronate (150 mg) for a period of 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging, and his colleagues.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. This questionnaire included four domains: convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction or less bother/lower frequency of side effects. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of the women preferred once-monthly ibandronate, whereas 8% preferred once-weekly therapy and 5% did not cite a preference. The remainder of patient responses were not evaluable. Overall, 70% of patients (1,087 out of 1,543) in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, compared with previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly ibandronate doses. Experience of stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy was associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies involving researchers from Merck & Co. Inc. (maker of Fosamax), once-monthly ibandronate seemed to offer no advantage in persistence over once-weekly alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research, Merck & Co. Inc., and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription drug information for more than 150 million unique patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new (index) prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. They were excluded if they had a prescription for any bisphosphonate during the 12 months before the index date, in order to focus only on newly treated patients. All of the women were followed for 1 year. They were considered persistent users if they did not have a therapy break of more than 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate, respectively, had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, compared with those on weekly alendronate.

“The results of this analysis suggest that persistency rates are not improved by monthly dosing of oral bisphosphonates versus weekly dosing,” the authors wrote.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonate therapy. The data come from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. For this study, the researchers contracted with a large pharmacy with more than 3,000 stores in 28 states.

Potential participants were identified by their retail pharmacy dispensing records. Patients were initially defined as persisters if they filled their bisphosphonate prescriptions at least five times in a 17-month period. Persistence was confirmed using the interview process. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the efficacy of osteoporosis drugs and the absence of side effects and drug interactions were strong determinants of persistence with bisphosphonate therapy. In all, 93% of weekly persisters reported belief in the drug's effectiveness, compared with 88% of monthly persisters. In both groups, 83% reported an absence of side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Weekly and monthly persisters were equally likely to report out-of-pocket costs and remembering to take the bisphosphonates as their biggest problems. Altogether, 45% of weekly persisters and 52% of monthly persisters reported out-of-pocket costs being a problem. And 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Dosing frequency was not cited as a problem by many in either group—13% of weekly persisters and 7% of monthly persisters. “The DASH study suggests that the major drivers of persistency with bisphosphonates are belief in the effectiveness of the therapy and the lack of side effects and drug interactions, not dosing frequency,” the researchers wrote.

Compliance is key to successful treatment with these drugs because bioavailability is notoriously poor.

Under optimal conditions—when patients follow dosing instructions perfectly—bioavailability of oral bisphosphonates is minuscule. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours before breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding for a patient. Patients on alendronate and risedronate should take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications, and they should not lie down for 30 minutes after taking either of these drugs.

Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients should not to lie down for 60 minutes after taking the drug.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves greatly the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by about 40% when taken either 30 minutes or 1 hour before breakfast, when compared with dosing 2 hours before eating. The package labeling for alendronate also notes that “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice when alendronate is taken reduces bioavailability by about 60% as well.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, compared with dosing in the fasting state. Dosing 1 hour before breakfast reduces the extent of absorption by 30%, compared with dosing in the fasting state. Dosing either half an hour before breakfast or 2 hours after dinner results in a similar extent of absorption.

For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, in comparison with that observed in fasted patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are taken less than 60 minutes after an ibandronate dose.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — With billions of dollars at stake and the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are emerging all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For the oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). And the answer depends on whom you ask, judging from four poster presentations.

Two studies involving researchers from Roche Laboratories Inc. (codeveloper of Boniva, along with GlaxoSmithKline) suggested that not only did women prefer once-monthly ibandronate but they were also more likely to persist with the drug than were those on once-weekly alendronate or risedronate.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and his colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate.

The unadjusted 9-month persistence rates were 41% for patients receiving monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy.

Monthly ibandronate users were 31% more likely to be persistent with therapy, compared with those on weekly alendronate or risedronate, after controlling for age, copay, comorbidities, and prescriptions greater than a 30-day supply. “After accounting for potential confounding factors, the increased likelihood of persistence reflects the independent effect of dosing frequency on patient persistence,” the researchers wrote.

In the second study, postmenopausal women were enrolled in a prospective, open-label study if they had been receiving once-weekly alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for a minimum of 3 months. The women were given once-monthly ibandronate (150 mg) for a period of 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging, and his colleagues.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. This questionnaire included four domains: convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction or less bother/lower frequency of side effects. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of the women preferred once-monthly ibandronate, whereas 8% preferred once-weekly therapy and 5% did not cite a preference. The remainder of patient responses were not evaluable. Overall, 70% of patients (1,087 out of 1,543) in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, compared with previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly ibandronate doses. Experience of stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy was associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies involving researchers from Merck & Co. Inc. (maker of Fosamax), once-monthly ibandronate seemed to offer no advantage in persistence over once-weekly alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research, Merck & Co. Inc., and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription drug information for more than 150 million unique patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new (index) prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. They were excluded if they had a prescription for any bisphosphonate during the 12 months before the index date, in order to focus only on newly treated patients. All of the women were followed for 1 year. They were considered persistent users if they did not have a therapy break of more than 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate, respectively, had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, compared with those on weekly alendronate.

“The results of this analysis suggest that persistency rates are not improved by monthly dosing of oral bisphosphonates versus weekly dosing,” the authors wrote.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonate therapy. The data come from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. For this study, the researchers contracted with a large pharmacy with more than 3,000 stores in 28 states.

Potential participants were identified by their retail pharmacy dispensing records. Patients were initially defined as persisters if they filled their bisphosphonate prescriptions at least five times in a 17-month period. Persistence was confirmed using the interview process. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the efficacy of osteoporosis drugs and the absence of side effects and drug interactions were strong determinants of persistence with bisphosphonate therapy. In all, 93% of weekly persisters reported belief in the drug's effectiveness, compared with 88% of monthly persisters. In both groups, 83% reported an absence of side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Weekly and monthly persisters were equally likely to report out-of-pocket costs and remembering to take the bisphosphonates as their biggest problems. Altogether, 45% of weekly persisters and 52% of monthly persisters reported out-of-pocket costs being a problem. And 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Dosing frequency was not cited as a problem by many in either group—13% of weekly persisters and 7% of monthly persisters. “The DASH study suggests that the major drivers of persistency with bisphosphonates are belief in the effectiveness of the therapy and the lack of side effects and drug interactions, not dosing frequency,” the researchers wrote.

Compliance is key to successful treatment with these drugs because bioavailability is notoriously poor.

Under optimal conditions—when patients follow dosing instructions perfectly—bioavailability of oral bisphosphonates is minuscule. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours before breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding for a patient. Patients on alendronate and risedronate should take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications, and they should not lie down for 30 minutes after taking either of these drugs.

Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients should not to lie down for 60 minutes after taking the drug.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves greatly the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by about 40% when taken either 30 minutes or 1 hour before breakfast, when compared with dosing 2 hours before eating. The package labeling for alendronate also notes that “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice when alendronate is taken reduces bioavailability by about 60% as well.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, compared with dosing in the fasting state. Dosing 1 hour before breakfast reduces the extent of absorption by 30%, compared with dosing in the fasting state. Dosing either half an hour before breakfast or 2 hours after dinner results in a similar extent of absorption.

For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, in comparison with that observed in fasted patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are taken less than 60 minutes after an ibandronate dose.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — With billions of dollars at stake and the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are emerging all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For the oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). And the answer depends on whom you ask, judging from four poster presentations.

Two studies involving researchers from Roche Laboratories Inc. (codeveloper of Boniva, along with GlaxoSmithKline) suggested that not only did women prefer once-monthly ibandronate but they were also more likely to persist with the drug than were those on once-weekly alendronate or risedronate.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and his colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate.

The unadjusted 9-month persistence rates were 41% for patients receiving monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy.

Monthly ibandronate users were 31% more likely to be persistent with therapy, compared with those on weekly alendronate or risedronate, after controlling for age, copay, comorbidities, and prescriptions greater than a 30-day supply. “After accounting for potential confounding factors, the increased likelihood of persistence reflects the independent effect of dosing frequency on patient persistence,” the researchers wrote.

In the second study, postmenopausal women were enrolled in a prospective, open-label study if they had been receiving once-weekly alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for a minimum of 3 months. The women were given once-monthly ibandronate (150 mg) for a period of 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging, and his colleagues.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. This questionnaire included four domains: convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction or less bother/lower frequency of side effects. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of the women preferred once-monthly ibandronate, whereas 8% preferred once-weekly therapy and 5% did not cite a preference. The remainder of patient responses were not evaluable. Overall, 70% of patients (1,087 out of 1,543) in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, compared with previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly ibandronate doses. Experience of stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy was associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies involving researchers from Merck & Co. Inc. (maker of Fosamax), once-monthly ibandronate seemed to offer no advantage in persistence over once-weekly alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research, Merck & Co. Inc., and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription drug information for more than 150 million unique patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new (index) prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. They were excluded if they had a prescription for any bisphosphonate during the 12 months before the index date, in order to focus only on newly treated patients. All of the women were followed for 1 year. They were considered persistent users if they did not have a therapy break of more than 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate, respectively, had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, compared with those on weekly alendronate.

“The results of this analysis suggest that persistency rates are not improved by monthly dosing of oral bisphosphonates versus weekly dosing,” the authors wrote.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonate therapy. The data come from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. For this study, the researchers contracted with a large pharmacy with more than 3,000 stores in 28 states.

Potential participants were identified by their retail pharmacy dispensing records. Patients were initially defined as persisters if they filled their bisphosphonate prescriptions at least five times in a 17-month period. Persistence was confirmed using the interview process. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the efficacy of osteoporosis drugs and the absence of side effects and drug interactions were strong determinants of persistence with bisphosphonate therapy. In all, 93% of weekly persisters reported belief in the drug's effectiveness, compared with 88% of monthly persisters. In both groups, 83% reported an absence of side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Weekly and monthly persisters were equally likely to report out-of-pocket costs and remembering to take the bisphosphonates as their biggest problems. Altogether, 45% of weekly persisters and 52% of monthly persisters reported out-of-pocket costs being a problem. And 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Dosing frequency was not cited as a problem by many in either group—13% of weekly persisters and 7% of monthly persisters. “The DASH study suggests that the major drivers of persistency with bisphosphonates are belief in the effectiveness of the therapy and the lack of side effects and drug interactions, not dosing frequency,” the researchers wrote.

Compliance is key to successful treatment with these drugs because bioavailability is notoriously poor.

Under optimal conditions—when patients follow dosing instructions perfectly—bioavailability of oral bisphosphonates is minuscule. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours before breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding for a patient. Patients on alendronate and risedronate should take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications, and they should not lie down for 30 minutes after taking either of these drugs.

Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients should not to lie down for 60 minutes after taking the drug.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves greatly the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by about 40% when taken either 30 minutes or 1 hour before breakfast, when compared with dosing 2 hours before eating. The package labeling for alendronate also notes that “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice when alendronate is taken reduces bioavailability by about 60% as well.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, compared with dosing in the fasting state. Dosing 1 hour before breakfast reduces the extent of absorption by 30%, compared with dosing in the fasting state. Dosing either half an hour before breakfast or 2 hours after dinner results in a similar extent of absorption.

For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, in comparison with that observed in fasted patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are taken less than 60 minutes after an ibandronate dose.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Not only does duloxetine appear to reduce the severity of pain, especially during the night, the drug may also help patients with diabetic peripheral neuropathy get a better night's sleep, according to a poster presentation at the annual meeting of the American Pain Society.

After 12 weeks of treatment, patients on 60 mg of duloxetine once or twice daily had improvements in average daily pain severity, night pain severity, and pain-related sleep interference, wrote Dr. David A. Fishbain, professor of psychiatry and behavioral sciences at the University of Miami, and his colleagues at Eli Lilly, maker of duloxetine (Cymbalta).

Although causality cannot be demonstrated between duloxetine and better sleep, the findings suggest that improvements in pain will be associated with less interference in sleep, the authors wrote.

The researchers pooled data from three double-blind, placebo-controlled trials of duloxetine in patients with diabetic peripheral neuropathic pain (DPNP). In the first study, 457 patients were randomized to receive 20 mg of duloxetine once daily, 60 mg of duloxetine once or twice daily, or placebo. In studies two and three, 334 and 348 patients, respectively, were randomized to receive 60 mg of duloxetine once daily, 60 mg of duloxetine twice daily, or placebo.

Although the primary efficacy measure for the studies was the reduction in the weekly mean of the 24-hour average pain score, secondary end points included average daily night pain severity (measured on an 11-point Likert scale) and the Brief Pain Inventory sleep interference item.

Patients were included in the trials if they were 18 years or older with pain due to bilateral peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Pain had to have begun in the feet with relatively symmetric onset. Diagnosis was confirmed by a score of at least three on the Michigan Neuropathy Screening Instrument. Daily pain had to be present for at least 6 months. Patients also had to have at least a 4 on the 24-hour average pain severity (11-point Likert) scale and stable glycemic control. Notably, patients with a current or recent (within the last year) diagnosis of major depressive disorder as defined by the DSM-IV were excluded from the studies.

The researchers identified a subset of nonsomnolent patients by excluding those who reported treatment-emergent somnolence or who were on concomitant sedating medications. Treatment-emergent somnolence included reports of daytime sleepiness, drowsiness, being drowsy upon awakening, excessive daytime sleepiness, a feeling of residual sleepiness, groggy, groggy and sluggish, groggy on awakening, hard to awaken, less alert on rising, sleepiness, sleepy, and somnolence.

In all three studies, 339 patients received placebo. Of these, 307 met the criteria for the nonsomnolent subset. A total of 685 patients received 60 mg or 120 mg per day of duloxetine in all three studies. Of these, 607 met the criteria for the nonsomnolent subset.

Patients in the nonsomnolent/nonsedating subgroup who were on duloxetine showed improvements in daily average pain and night pain severity, compared with those on placebo. The improvements started as early as 1 week and were maintained for 12 weeks. At 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in daily average pain severity of 47% and 50%, respectively, compared with 29% for those on placebo.

Duloxetine also reduced pain-related sleep interference at 4, 8, and 12 weeks. At 12 weeks, patients on 60 mg of duloxetine once and twice daily had reductions in pain-related sleep interference of 55% and 57%, respectively, compared with 45% for those on placebo.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Not only does duloxetine appear to reduce the severity of pain, especially during the night, the drug may also help patients with diabetic peripheral neuropathy get a better night's sleep, according to a poster presentation at the annual meeting of the American Pain Society.

After 12 weeks of treatment, patients on 60 mg of duloxetine once or twice daily had improvements in average daily pain severity, night pain severity, and pain-related sleep interference, wrote Dr. David A. Fishbain, professor of psychiatry and behavioral sciences at the University of Miami, and his colleagues at Eli Lilly, maker of duloxetine (Cymbalta).

Although causality cannot be demonstrated between duloxetine and better sleep, the findings suggest that improvements in pain will be associated with less interference in sleep, the authors wrote.

The researchers pooled data from three double-blind, placebo-controlled trials of duloxetine in patients with diabetic peripheral neuropathic pain (DPNP). In the first study, 457 patients were randomized to receive 20 mg of duloxetine once daily, 60 mg of duloxetine once or twice daily, or placebo. In studies two and three, 334 and 348 patients, respectively, were randomized to receive 60 mg of duloxetine once daily, 60 mg of duloxetine twice daily, or placebo.

Although the primary efficacy measure for the studies was the reduction in the weekly mean of the 24-hour average pain score, secondary end points included average daily night pain severity (measured on an 11-point Likert scale) and the Brief Pain Inventory sleep interference item.

Patients were included in the trials if they were 18 years or older with pain due to bilateral peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Pain had to have begun in the feet with relatively symmetric onset. Diagnosis was confirmed by a score of at least three on the Michigan Neuropathy Screening Instrument. Daily pain had to be present for at least 6 months. Patients also had to have at least a 4 on the 24-hour average pain severity (11-point Likert) scale and stable glycemic control. Notably, patients with a current or recent (within the last year) diagnosis of major depressive disorder as defined by the DSM-IV were excluded from the studies.

The researchers identified a subset of nonsomnolent patients by excluding those who reported treatment-emergent somnolence or who were on concomitant sedating medications. Treatment-emergent somnolence included reports of daytime sleepiness, drowsiness, being drowsy upon awakening, excessive daytime sleepiness, a feeling of residual sleepiness, groggy, groggy and sluggish, groggy on awakening, hard to awaken, less alert on rising, sleepiness, sleepy, and somnolence.

In all three studies, 339 patients received placebo. Of these, 307 met the criteria for the nonsomnolent subset. A total of 685 patients received 60 mg or 120 mg per day of duloxetine in all three studies. Of these, 607 met the criteria for the nonsomnolent subset.

Patients in the nonsomnolent/nonsedating subgroup who were on duloxetine showed improvements in daily average pain and night pain severity, compared with those on placebo. The improvements started as early as 1 week and were maintained for 12 weeks. At 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in daily average pain severity of 47% and 50%, respectively, compared with 29% for those on placebo.

Duloxetine also reduced pain-related sleep interference at 4, 8, and 12 weeks. At 12 weeks, patients on 60 mg of duloxetine once and twice daily had reductions in pain-related sleep interference of 55% and 57%, respectively, compared with 45% for those on placebo.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Not only does duloxetine appear to reduce the severity of pain, especially during the night, the drug may also help patients with diabetic peripheral neuropathy get a better night's sleep, according to a poster presentation at the annual meeting of the American Pain Society.

After 12 weeks of treatment, patients on 60 mg of duloxetine once or twice daily had improvements in average daily pain severity, night pain severity, and pain-related sleep interference, wrote Dr. David A. Fishbain, professor of psychiatry and behavioral sciences at the University of Miami, and his colleagues at Eli Lilly, maker of duloxetine (Cymbalta).

Although causality cannot be demonstrated between duloxetine and better sleep, the findings suggest that improvements in pain will be associated with less interference in sleep, the authors wrote.

The researchers pooled data from three double-blind, placebo-controlled trials of duloxetine in patients with diabetic peripheral neuropathic pain (DPNP). In the first study, 457 patients were randomized to receive 20 mg of duloxetine once daily, 60 mg of duloxetine once or twice daily, or placebo. In studies two and three, 334 and 348 patients, respectively, were randomized to receive 60 mg of duloxetine once daily, 60 mg of duloxetine twice daily, or placebo.

Although the primary efficacy measure for the studies was the reduction in the weekly mean of the 24-hour average pain score, secondary end points included average daily night pain severity (measured on an 11-point Likert scale) and the Brief Pain Inventory sleep interference item.

Patients were included in the trials if they were 18 years or older with pain due to bilateral peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Pain had to have begun in the feet with relatively symmetric onset. Diagnosis was confirmed by a score of at least three on the Michigan Neuropathy Screening Instrument. Daily pain had to be present for at least 6 months. Patients also had to have at least a 4 on the 24-hour average pain severity (11-point Likert) scale and stable glycemic control. Notably, patients with a current or recent (within the last year) diagnosis of major depressive disorder as defined by the DSM-IV were excluded from the studies.

The researchers identified a subset of nonsomnolent patients by excluding those who reported treatment-emergent somnolence or who were on concomitant sedating medications. Treatment-emergent somnolence included reports of daytime sleepiness, drowsiness, being drowsy upon awakening, excessive daytime sleepiness, a feeling of residual sleepiness, groggy, groggy and sluggish, groggy on awakening, hard to awaken, less alert on rising, sleepiness, sleepy, and somnolence.

In all three studies, 339 patients received placebo. Of these, 307 met the criteria for the nonsomnolent subset. A total of 685 patients received 60 mg or 120 mg per day of duloxetine in all three studies. Of these, 607 met the criteria for the nonsomnolent subset.

Patients in the nonsomnolent/nonsedating subgroup who were on duloxetine showed improvements in daily average pain and night pain severity, compared with those on placebo. The improvements started as early as 1 week and were maintained for 12 weeks. At 12 weeks, subset patients on 60 mg of duloxetine once and twice daily had improvements in daily average pain severity of 47% and 50%, respectively, compared with 29% for those on placebo.

Duloxetine also reduced pain-related sleep interference at 4, 8, and 12 weeks. At 12 weeks, patients on 60 mg of duloxetine once and twice daily had reductions in pain-related sleep interference of 55% and 57%, respectively, compared with 45% for those on placebo.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A careful evaluation and thorough history can identify a large portion of secondary osteoporosis patients, Dr. Meryl LeBoff, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women's Hospital in Boston, said at an international symposium sponsored by the National Osteoporosis Foundation.

The true prevalence of secondary osteoporosis is not known. However, about 50% of patients can be detected with a good medical history, said Dr. LeBoff. While laboratory evaluations vary, such tests can be used to identify 25%–65% of patients with secondary osteoporosis.

Identifying secondary osteoporosis is crucial because skeletal changes may be reversible and decreased acquisition of peak bone mass is a determinant of osteoporosis later in life.

In a 2004 report on bone health and osteoporosis, the surgeon general recommended that all patients diagnosed with osteoporosis get at least a limited evaluation for secondary causes of bone loss.

In particular, premenopausal women or men with unexplained fractures and those who are adherent but have a poor response to therapy should be evaluated for secondary osteoporosis.

A low z score—which compares a patient's bone mineral density (BMD) to the mean for a healthy age- and gender-matched population—may suggest an increased likelihood of secondary osteoporosis. A z score of −1.0 is tied to a twofold greater lifetime risk of fracture and a z score of −2.0 is associated with a fourfold greater lifetime risk of fracture. Patients with a low z score are most in need of in-depth evaluation for secondary osteoporosis.

“However, z scores do not consistently predict which patient has an underlying disorder, so it's important to use clinical judgement in the evaluation of a particular patient,” said Dr. LeBoff.

There are no evidence-based guides for evaluating a patient for secondary osteoporosis. Dr. LeBoff recommends a detailed personal and family history. Be sure to ask about calcium intake. In addition to a thorough physical exam, do bone density testing and laboratory tests.

Laboratory tests for serum calcium, 25-hydroxy vitamin D, 24-hour urinary calcium, and parathyroid hormone—plus serum thyroid-stimulating hormone among women on thyroid replacement—can identify an estimated 98% of patients with secondary osteoporosis (J. Clin. Endocrinol. Metab. 2002;87:4431–7).

At the Brigham and Women's osteoporosis center, evaluation guidelines for secondary osteoporosis include a z score less than −1.5. Laboratory tests include serum calcium and phosphorus, renal function, 25-hydroxy vitamin D levels, thyroid-stimulating hormone, parathyroid hormone, and urinary calcium. In select patients, bone turnover markers are tested.

Dr. LeBoff also discussed some common causes of secondary osteoporosis:

▸ Glucocorticoids. “Use of glucocorticoids is the most common cause of secondary osteoporosis,” said Dr. LeBoff. A number of other endocrine abnormalities—thyroid hormone excess, hypogonadism, anorexia, hyperparathyroidism, hypercalciuria, vitamin D deficiency, and androgen insensitivity—can also cause secondary osteoporosis.

Glucocorticoids increase fracture risk progressively. “Even extremely low doses of inhaled glucocorticoids can lead to bone loss,” said Dr. LeBoff.

The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, involving decreased osteoblast function, increased osteoblast apoptosis, increased gastrointestinal absorption of calcium, increased urinary calcium excretion, and an increase in osteoclast bone resorption.

▸ Anorexia. This disorder affects an estimated 4% of U.S. college students and leads to a 25% lower spine BMD and a sevenfold increased fracture risk. Peak bone mass is decreased and there may be a permanent deficit of bone mass. Anorexic women have subnormal levels of dehydroepiandrosterone, testosterone, estrogen, and cortisol. “Estrogen does not correct the low bone mass [in these women],” said Dr. LeBoff. A number of trials attempting to reverse lost bone mass in anorexic women are underway.

▸ Vitamin D deficiency. Vitamin D deficiency is common and has been implicated in impaired muscle function, increased falls, increased muscle pain, multiple sclerosis, and some malignancies. There is seasonal variation in vitamin D levels. Notably, vitamin D activation decreases with age, darker skin pigment, and increased sunblock use. Gastrointestinal disorders can lead to vitamin D deficiency, as it is absorbed in the small intestine.

“Vitamin D deficiency is currently defined as 25-hydroxy vitamin D level of less than 20 ng/mL … sufficiency for bone is [25-hydroxy vitamin D level] greater than 30–32 ng/mL,” said Dr. LeBoff.

Inadequate levels of vitamin D have been documented in 52% of women who participated in osteoporosis trials. Women in these studies had an average T score of −1.8.

In a study at Brigham and Women's, 90% of women admitted with hip fractures had vitamin D insufficiency and 57% had vitamin D deficiency. Because of this, when women are admitted now with hip fragility fracture they are given 50,000 units of vitamin D. They are also evaluated for secondary osteoporosis.

▸ Aromatase inhibitors. “Bone loss is clearly associated with breast cancer therapies,” said Dr. LeBoff. Aromatase inhibitors can lead to bone loss of about 2.6% per year, though long-term data are not yet available. Gonadotropin-releasing hormones can lead to bone loss of 4%–6% per year. Ovarian failure can lead to bone loss of about 8% per year. Oophorectomy is associated with bone loss of 11% per year.

WASHINGTON — A careful evaluation and thorough history can identify a large portion of secondary osteoporosis patients, Dr. Meryl LeBoff, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women's Hospital in Boston, said at an international symposium sponsored by the National Osteoporosis Foundation.

The true prevalence of secondary osteoporosis is not known. However, about 50% of patients can be detected with a good medical history, said Dr. LeBoff. While laboratory evaluations vary, such tests can be used to identify 25%–65% of patients with secondary osteoporosis.

Identifying secondary osteoporosis is crucial because skeletal changes may be reversible and decreased acquisition of peak bone mass is a determinant of osteoporosis later in life.

In a 2004 report on bone health and osteoporosis, the surgeon general recommended that all patients diagnosed with osteoporosis get at least a limited evaluation for secondary causes of bone loss.

In particular, premenopausal women or men with unexplained fractures and those who are adherent but have a poor response to therapy should be evaluated for secondary osteoporosis.

A low z score—which compares a patient's bone mineral density (BMD) to the mean for a healthy age- and gender-matched population—may suggest an increased likelihood of secondary osteoporosis. A z score of −1.0 is tied to a twofold greater lifetime risk of fracture and a z score of −2.0 is associated with a fourfold greater lifetime risk of fracture. Patients with a low z score are most in need of in-depth evaluation for secondary osteoporosis.

“However, z scores do not consistently predict which patient has an underlying disorder, so it's important to use clinical judgement in the evaluation of a particular patient,” said Dr. LeBoff.

There are no evidence-based guides for evaluating a patient for secondary osteoporosis. Dr. LeBoff recommends a detailed personal and family history. Be sure to ask about calcium intake. In addition to a thorough physical exam, do bone density testing and laboratory tests.

Laboratory tests for serum calcium, 25-hydroxy vitamin D, 24-hour urinary calcium, and parathyroid hormone—plus serum thyroid-stimulating hormone among women on thyroid replacement—can identify an estimated 98% of patients with secondary osteoporosis (J. Clin. Endocrinol. Metab. 2002;87:4431–7).

At the Brigham and Women's osteoporosis center, evaluation guidelines for secondary osteoporosis include a z score less than −1.5. Laboratory tests include serum calcium and phosphorus, renal function, 25-hydroxy vitamin D levels, thyroid-stimulating hormone, parathyroid hormone, and urinary calcium. In select patients, bone turnover markers are tested.

Dr. LeBoff also discussed some common causes of secondary osteoporosis:

▸ Glucocorticoids. “Use of glucocorticoids is the most common cause of secondary osteoporosis,” said Dr. LeBoff. A number of other endocrine abnormalities—thyroid hormone excess, hypogonadism, anorexia, hyperparathyroidism, hypercalciuria, vitamin D deficiency, and androgen insensitivity—can also cause secondary osteoporosis.

Glucocorticoids increase fracture risk progressively. “Even extremely low doses of inhaled glucocorticoids can lead to bone loss,” said Dr. LeBoff.

The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, involving decreased osteoblast function, increased osteoblast apoptosis, increased gastrointestinal absorption of calcium, increased urinary calcium excretion, and an increase in osteoclast bone resorption.

▸ Anorexia. This disorder affects an estimated 4% of U.S. college students and leads to a 25% lower spine BMD and a sevenfold increased fracture risk. Peak bone mass is decreased and there may be a permanent deficit of bone mass. Anorexic women have subnormal levels of dehydroepiandrosterone, testosterone, estrogen, and cortisol. “Estrogen does not correct the low bone mass [in these women],” said Dr. LeBoff. A number of trials attempting to reverse lost bone mass in anorexic women are underway.

▸ Vitamin D deficiency. Vitamin D deficiency is common and has been implicated in impaired muscle function, increased falls, increased muscle pain, multiple sclerosis, and some malignancies. There is seasonal variation in vitamin D levels. Notably, vitamin D activation decreases with age, darker skin pigment, and increased sunblock use. Gastrointestinal disorders can lead to vitamin D deficiency, as it is absorbed in the small intestine.

“Vitamin D deficiency is currently defined as 25-hydroxy vitamin D level of less than 20 ng/mL … sufficiency for bone is [25-hydroxy vitamin D level] greater than 30–32 ng/mL,” said Dr. LeBoff.

Inadequate levels of vitamin D have been documented in 52% of women who participated in osteoporosis trials. Women in these studies had an average T score of −1.8.

In a study at Brigham and Women's, 90% of women admitted with hip fractures had vitamin D insufficiency and 57% had vitamin D deficiency. Because of this, when women are admitted now with hip fragility fracture they are given 50,000 units of vitamin D. They are also evaluated for secondary osteoporosis.

▸ Aromatase inhibitors. “Bone loss is clearly associated with breast cancer therapies,” said Dr. LeBoff. Aromatase inhibitors can lead to bone loss of about 2.6% per year, though long-term data are not yet available. Gonadotropin-releasing hormones can lead to bone loss of 4%–6% per year. Ovarian failure can lead to bone loss of about 8% per year. Oophorectomy is associated with bone loss of 11% per year.

WASHINGTON — A careful evaluation and thorough history can identify a large portion of secondary osteoporosis patients, Dr. Meryl LeBoff, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women's Hospital in Boston, said at an international symposium sponsored by the National Osteoporosis Foundation.

The true prevalence of secondary osteoporosis is not known. However, about 50% of patients can be detected with a good medical history, said Dr. LeBoff. While laboratory evaluations vary, such tests can be used to identify 25%–65% of patients with secondary osteoporosis.

Identifying secondary osteoporosis is crucial because skeletal changes may be reversible and decreased acquisition of peak bone mass is a determinant of osteoporosis later in life.

In a 2004 report on bone health and osteoporosis, the surgeon general recommended that all patients diagnosed with osteoporosis get at least a limited evaluation for secondary causes of bone loss.

In particular, premenopausal women or men with unexplained fractures and those who are adherent but have a poor response to therapy should be evaluated for secondary osteoporosis.

A low z score—which compares a patient's bone mineral density (BMD) to the mean for a healthy age- and gender-matched population—may suggest an increased likelihood of secondary osteoporosis. A z score of −1.0 is tied to a twofold greater lifetime risk of fracture and a z score of −2.0 is associated with a fourfold greater lifetime risk of fracture. Patients with a low z score are most in need of in-depth evaluation for secondary osteoporosis.

“However, z scores do not consistently predict which patient has an underlying disorder, so it's important to use clinical judgement in the evaluation of a particular patient,” said Dr. LeBoff.

There are no evidence-based guides for evaluating a patient for secondary osteoporosis. Dr. LeBoff recommends a detailed personal and family history. Be sure to ask about calcium intake. In addition to a thorough physical exam, do bone density testing and laboratory tests.

Laboratory tests for serum calcium, 25-hydroxy vitamin D, 24-hour urinary calcium, and parathyroid hormone—plus serum thyroid-stimulating hormone among women on thyroid replacement—can identify an estimated 98% of patients with secondary osteoporosis (J. Clin. Endocrinol. Metab. 2002;87:4431–7).

At the Brigham and Women's osteoporosis center, evaluation guidelines for secondary osteoporosis include a z score less than −1.5. Laboratory tests include serum calcium and phosphorus, renal function, 25-hydroxy vitamin D levels, thyroid-stimulating hormone, parathyroid hormone, and urinary calcium. In select patients, bone turnover markers are tested.

Dr. LeBoff also discussed some common causes of secondary osteoporosis:

▸ Glucocorticoids. “Use of glucocorticoids is the most common cause of secondary osteoporosis,” said Dr. LeBoff. A number of other endocrine abnormalities—thyroid hormone excess, hypogonadism, anorexia, hyperparathyroidism, hypercalciuria, vitamin D deficiency, and androgen insensitivity—can also cause secondary osteoporosis.

Glucocorticoids increase fracture risk progressively. “Even extremely low doses of inhaled glucocorticoids can lead to bone loss,” said Dr. LeBoff.

The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, involving decreased osteoblast function, increased osteoblast apoptosis, increased gastrointestinal absorption of calcium, increased urinary calcium excretion, and an increase in osteoclast bone resorption.

▸ Anorexia. This disorder affects an estimated 4% of U.S. college students and leads to a 25% lower spine BMD and a sevenfold increased fracture risk. Peak bone mass is decreased and there may be a permanent deficit of bone mass. Anorexic women have subnormal levels of dehydroepiandrosterone, testosterone, estrogen, and cortisol. “Estrogen does not correct the low bone mass [in these women],” said Dr. LeBoff. A number of trials attempting to reverse lost bone mass in anorexic women are underway.

▸ Vitamin D deficiency. Vitamin D deficiency is common and has been implicated in impaired muscle function, increased falls, increased muscle pain, multiple sclerosis, and some malignancies. There is seasonal variation in vitamin D levels. Notably, vitamin D activation decreases with age, darker skin pigment, and increased sunblock use. Gastrointestinal disorders can lead to vitamin D deficiency, as it is absorbed in the small intestine.

“Vitamin D deficiency is currently defined as 25-hydroxy vitamin D level of less than 20 ng/mL … sufficiency for bone is [25-hydroxy vitamin D level] greater than 30–32 ng/mL,” said Dr. LeBoff.

Inadequate levels of vitamin D have been documented in 52% of women who participated in osteoporosis trials. Women in these studies had an average T score of −1.8.

In a study at Brigham and Women's, 90% of women admitted with hip fractures had vitamin D insufficiency and 57% had vitamin D deficiency. Because of this, when women are admitted now with hip fragility fracture they are given 50,000 units of vitamin D. They are also evaluated for secondary osteoporosis.

▸ Aromatase inhibitors. “Bone loss is clearly associated with breast cancer therapies,” said Dr. LeBoff. Aromatase inhibitors can lead to bone loss of about 2.6% per year, though long-term data are not yet available. Gonadotropin-releasing hormones can lead to bone loss of 4%–6% per year. Ovarian failure can lead to bone loss of about 8% per year. Oophorectomy is associated with bone loss of 11% per year.

WASHINGTON — With the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are popping up all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). The answer depends on whom you ask, judging from four poster presentations.

Two studies with researchers from Roche Laboratories Inc. (codeveloper of Boniva, with GlaxoSmithKline) suggested women prefer once-monthly ibandronate and are more likely to persist with it.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate. Persistence was assessed for a 9-month follow-up period.

The unadjusted 9-month persistence rates were 41% for patients on monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy. Monthly ibandronate users were 31% more likely to be persistent versus those on weekly drugs after controlling for age, copay, comorbidities, and prescriptions for more than a 30-day supply.

In a second study, postmenopausal women were enrolled in a prospective, open-label study if they'd been receiving alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for at least 3 months. The women were given once-monthly ibandronate (150 mg) for 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. The survey covered domains of convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of women preferred once-monthly ibandronate, while 8% preferred once-weekly therapy and 5% did not cite a preference. Overall, 70% in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, versus previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly doses. Stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy were associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies with researchers from Merck & Co. (maker of Fosamax), ibandronate offered no advantage in persistence over alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research for Merck and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription information for over 150 million patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. Women were excluded if they had a prescription for any bisphosphonate during the 12 months prior to the index date. All were followed for 1 year. They were considered persistent users if they did not have a therapy break of over 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate respectively had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, versus those on alendronate.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonates. The data came from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. In this study, the researchers worked with a large pharmacy (over 3,000 stores in 28 states).

Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.

WASHINGTON — With the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are popping up all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). The answer depends on whom you ask, judging from four poster presentations.

Two studies with researchers from Roche Laboratories Inc. (codeveloper of Boniva, with GlaxoSmithKline) suggested women prefer once-monthly ibandronate and are more likely to persist with it.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate. Persistence was assessed for a 9-month follow-up period.

The unadjusted 9-month persistence rates were 41% for patients on monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy. Monthly ibandronate users were 31% more likely to be persistent versus those on weekly drugs after controlling for age, copay, comorbidities, and prescriptions for more than a 30-day supply.

In a second study, postmenopausal women were enrolled in a prospective, open-label study if they'd been receiving alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for at least 3 months. The women were given once-monthly ibandronate (150 mg) for 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. The survey covered domains of convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of women preferred once-monthly ibandronate, while 8% preferred once-weekly therapy and 5% did not cite a preference. Overall, 70% in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, versus previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly doses. Stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy were associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies with researchers from Merck & Co. (maker of Fosamax), ibandronate offered no advantage in persistence over alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research for Merck and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription information for over 150 million patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. Women were excluded if they had a prescription for any bisphosphonate during the 12 months prior to the index date. All were followed for 1 year. They were considered persistent users if they did not have a therapy break of over 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate respectively had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, versus those on alendronate.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonates. The data came from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. In this study, the researchers worked with a large pharmacy (over 3,000 stores in 28 states).

Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.

WASHINGTON — With the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are popping up all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). The answer depends on whom you ask, judging from four poster presentations.

Two studies with researchers from Roche Laboratories Inc. (codeveloper of Boniva, with GlaxoSmithKline) suggested women prefer once-monthly ibandronate and are more likely to persist with it.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate. Persistence was assessed for a 9-month follow-up period.

The unadjusted 9-month persistence rates were 41% for patients on monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy. Monthly ibandronate users were 31% more likely to be persistent versus those on weekly drugs after controlling for age, copay, comorbidities, and prescriptions for more than a 30-day supply.

In a second study, postmenopausal women were enrolled in a prospective, open-label study if they'd been receiving alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for at least 3 months. The women were given once-monthly ibandronate (150 mg) for 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. The survey covered domains of convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of women preferred once-monthly ibandronate, while 8% preferred once-weekly therapy and 5% did not cite a preference. Overall, 70% in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, versus previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly doses. Stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy were associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies with researchers from Merck & Co. (maker of Fosamax), ibandronate offered no advantage in persistence over alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research for Merck and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription information for over 150 million patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. Women were excluded if they had a prescription for any bisphosphonate during the 12 months prior to the index date. All were followed for 1 year. They were considered persistent users if they did not have a therapy break of over 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate respectively had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, versus those on alendronate.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonates. The data came from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. In this study, the researchers worked with a large pharmacy (over 3,000 stores in 28 states).

Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.

SNOWMASS, COLO. — The most common pitfall in diagnosing vasculitides is failure to ask about the size of the involved blood vessels, Dr. John H. Stone said at a symposium sponsored by the American College of Rheumatology.

“That's really the key to sorting out these diseases clinically,” said Dr. Stone, a rheumatologist at Massachusetts General Hospital in Boston.

Large-vessel diseases can be excluded because vessels larger than 150 mcm are not present in the skin and very rarely lead to cutaneous findings. Medium-size vessels (50–150 mcm) have muscular walls, and some can be visualized. Small vessels (under 50 mcm) can't be visualized.

Vasculitides can be classified by the size of involved vessels: pure small vessel, pure medium vessel, and small/medium vessel overlap, he said.

Pure small-vessel vasculitides include Henoch-Schönlein purpura, hypersensitivity vasculitis, and hypocomplementemic urticarial vasculitis. Signs include palpable and nonpalpable purpura, pustules, urticarial lesions, and blisters.

Pure medium-vessel vasculitides include polyarteritis nodosa and Buerger's disease. Medium-vessel lesions include nodules, ulcers, livedo reticularis, and digital ischemia. “Medium-size vessels, down deep in the dermis and in the fat, cause skin lesions that typically heal with scarring,” said Dr. Stone.

There are two categories of small/medium vessel vasculitides: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and cryoglobulinemia. ANCA-associated vasculitides include Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and drug-induced ANCA-associated vasculitis.

SNOWMASS, COLO. — The most common pitfall in diagnosing vasculitides is failure to ask about the size of the involved blood vessels, Dr. John H. Stone said at a symposium sponsored by the American College of Rheumatology.

“That's really the key to sorting out these diseases clinically,” said Dr. Stone, a rheumatologist at Massachusetts General Hospital in Boston.

Large-vessel diseases can be excluded because vessels larger than 150 mcm are not present in the skin and very rarely lead to cutaneous findings. Medium-size vessels (50–150 mcm) have muscular walls, and some can be visualized. Small vessels (under 50 mcm) can't be visualized.

Vasculitides can be classified by the size of involved vessels: pure small vessel, pure medium vessel, and small/medium vessel overlap, he said.

Pure small-vessel vasculitides include Henoch-Schönlein purpura, hypersensitivity vasculitis, and hypocomplementemic urticarial vasculitis. Signs include palpable and nonpalpable purpura, pustules, urticarial lesions, and blisters.

Pure medium-vessel vasculitides include polyarteritis nodosa and Buerger's disease. Medium-vessel lesions include nodules, ulcers, livedo reticularis, and digital ischemia. “Medium-size vessels, down deep in the dermis and in the fat, cause skin lesions that typically heal with scarring,” said Dr. Stone.

There are two categories of small/medium vessel vasculitides: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and cryoglobulinemia. ANCA-associated vasculitides include Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and drug-induced ANCA-associated vasculitis.

SNOWMASS, COLO. — The most common pitfall in diagnosing vasculitides is failure to ask about the size of the involved blood vessels, Dr. John H. Stone said at a symposium sponsored by the American College of Rheumatology.

“That's really the key to sorting out these diseases clinically,” said Dr. Stone, a rheumatologist at Massachusetts General Hospital in Boston.

Large-vessel diseases can be excluded because vessels larger than 150 mcm are not present in the skin and very rarely lead to cutaneous findings. Medium-size vessels (50–150 mcm) have muscular walls, and some can be visualized. Small vessels (under 50 mcm) can't be visualized.

Vasculitides can be classified by the size of involved vessels: pure small vessel, pure medium vessel, and small/medium vessel overlap, he said.

Pure small-vessel vasculitides include Henoch-Schönlein purpura, hypersensitivity vasculitis, and hypocomplementemic urticarial vasculitis. Signs include palpable and nonpalpable purpura, pustules, urticarial lesions, and blisters.

Pure medium-vessel vasculitides include polyarteritis nodosa and Buerger's disease. Medium-vessel lesions include nodules, ulcers, livedo reticularis, and digital ischemia. “Medium-size vessels, down deep in the dermis and in the fat, cause skin lesions that typically heal with scarring,” said Dr. Stone.

There are two categories of small/medium vessel vasculitides: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and cryoglobulinemia. ANCA-associated vasculitides include Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and drug-induced ANCA-associated vasculitis.