Nancy Walsh

TORONTO — Aortic calcification was found to be an independent predictor of accelerated bone loss and hip fracture among postmenopausal women in a prospective epidemiologic study, Dr. Laszlo B. Tanko said at a world congress on osteoporosis.

Epidemiologic studies have suggested a link between cardiovascular disease and osteoporosis, two conditions that clearly are major contributors to morbidity and mortality in the elderly, but whether atherosclerosis is an independent contributor to fracture risk had not yet been determined, Dr. Tanko said. In the first long-term study addressing the questions of whether the severity and progression of aortic calcification might be associated with bone loss and fracture risk, Dr. Tanko and his colleagues from the Center for Clinical and Basic Research, Ballerup, Denmark, analyzed data from the Danish Prospective Epidemiological Risk Factors study.

In this study of 2,662 postmenopausal women, investigators identified classic cardiovascular risk factors in a baseline interview. They assessed aortic calcification using lateral x-rays and scored any calcification according to the Framingham system. Lumbar spine and total hip bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry.

A total of 1,877 patients had normal aortic calcification scores (below 3) at baseline, while 785 had scores of 3 or higher. Mean score among those in the group with lower scores was 0.4, compared with 6.5 among those in the higher-scores group.

Those with advanced aortic calcification at baseline subsequently had annual rates of progression of atherosclerotic burden that were approximately 2.5 higher than did those with normal calcification at baseline, Dr. Tanko said at the meeting, which was sponsored by the International Osteoporosis Foundation.

BMD scores at baseline for lumbar spine and hip were significantly lower among women with advanced atherosclerosis, with means of 0.84 g/cm

These differences were independent of age and body mass index, he said.

Accelerated subsequent rates of bone loss were seen among women with advanced atherosclerosis but not among those who were normal at baseline.

But at the lumbar spine, increases in BMD, rather than decreases, were seen among the advanced atherosclerosis group. An explanation for this may lie in the fact that the local blood supply to the proximal femur is unilateral, delicate, and more vulnerable to impaired blood flow than is blood supply to the vertebrae. Vertebral blood supply is bilateral and more advanced in terms of compensating for arterial obstruction, Dr. Tanko said.

During the study follow-up period, which averaged 7.5 years, there were 431 incident vertebral fractures and 37 incident hip fractures. There also were 113 acute cardiovascular events.

On multivariate regression analysis, there was a slightly increased but not statistically significant risk (relative risk 1.2) of vertebral fractures among those with advanced aortic calcification at baseline. Hip fracture risk, however, was 2.3-fold increased among those with higher calcification, compared with those whose calcification scores were normal at baseline. Regression analysis also showed that women with higher calcification also had a 2.5-fold increased risk of a cardiovascular event.

“We can say that aortic calcification is an independent predictor of accelerated bone loss and incident fracture at the hip but not at the vertebra. We are tempted to speculate that antiatherogenic measures might help decrease not only cardiovascular disease but also might help prevent fractures,” Dr. Tanko said.

In the question and answer session following Dr. Tanko's presentation, an audience member asked if he had considered the possibility that both atherosclerosis and bone loss are associated with a single common factor such as a cytokine cascade, or whether the bone loss might be causing atherosclerosis.

Dr. Tanko acknowledged that although he could not exclude systemic factors such as the impact of proinflammatory cytokines, he believed that his findings more clearly demonstrate the direct impact of ischemic atherosclerotic vascular disease on local bone metabolism.

He recently wrote that the underlying mechanism linking osteoporosis and cardiovascular disease is not yet fully understood, but “it seems reasonable to presume that the independent association reflects either a direct contribution of ischemic vascular disease to bone turnover or common pathomechanisms acting simultaneously on both bone and vascular cells. As for the latter option, proinflammatory cytokines such as IL-6 and TNF-α are known to exert proatherogenic effects, but they may also enhance osteoclastogenesis and consequently increased bone resorption” (J. Intern. Med. 2006;259:598–605).

Heavy calcification of the aortic wall (red arrows) at its site of bifurcation. Courtesy Dr. Laszlo B. Tanko

TORONTO — Aortic calcification was found to be an independent predictor of accelerated bone loss and hip fracture among postmenopausal women in a prospective epidemiologic study, Dr. Laszlo B. Tanko said at a world congress on osteoporosis.

Epidemiologic studies have suggested a link between cardiovascular disease and osteoporosis, two conditions that clearly are major contributors to morbidity and mortality in the elderly, but whether atherosclerosis is an independent contributor to fracture risk had not yet been determined, Dr. Tanko said. In the first long-term study addressing the questions of whether the severity and progression of aortic calcification might be associated with bone loss and fracture risk, Dr. Tanko and his colleagues from the Center for Clinical and Basic Research, Ballerup, Denmark, analyzed data from the Danish Prospective Epidemiological Risk Factors study.

In this study of 2,662 postmenopausal women, investigators identified classic cardiovascular risk factors in a baseline interview. They assessed aortic calcification using lateral x-rays and scored any calcification according to the Framingham system. Lumbar spine and total hip bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry.

A total of 1,877 patients had normal aortic calcification scores (below 3) at baseline, while 785 had scores of 3 or higher. Mean score among those in the group with lower scores was 0.4, compared with 6.5 among those in the higher-scores group.

Those with advanced aortic calcification at baseline subsequently had annual rates of progression of atherosclerotic burden that were approximately 2.5 higher than did those with normal calcification at baseline, Dr. Tanko said at the meeting, which was sponsored by the International Osteoporosis Foundation.

BMD scores at baseline for lumbar spine and hip were significantly lower among women with advanced atherosclerosis, with means of 0.84 g/cm

These differences were independent of age and body mass index, he said.

Accelerated subsequent rates of bone loss were seen among women with advanced atherosclerosis but not among those who were normal at baseline.

But at the lumbar spine, increases in BMD, rather than decreases, were seen among the advanced atherosclerosis group. An explanation for this may lie in the fact that the local blood supply to the proximal femur is unilateral, delicate, and more vulnerable to impaired blood flow than is blood supply to the vertebrae. Vertebral blood supply is bilateral and more advanced in terms of compensating for arterial obstruction, Dr. Tanko said.

During the study follow-up period, which averaged 7.5 years, there were 431 incident vertebral fractures and 37 incident hip fractures. There also were 113 acute cardiovascular events.

On multivariate regression analysis, there was a slightly increased but not statistically significant risk (relative risk 1.2) of vertebral fractures among those with advanced aortic calcification at baseline. Hip fracture risk, however, was 2.3-fold increased among those with higher calcification, compared with those whose calcification scores were normal at baseline. Regression analysis also showed that women with higher calcification also had a 2.5-fold increased risk of a cardiovascular event.

“We can say that aortic calcification is an independent predictor of accelerated bone loss and incident fracture at the hip but not at the vertebra. We are tempted to speculate that antiatherogenic measures might help decrease not only cardiovascular disease but also might help prevent fractures,” Dr. Tanko said.

In the question and answer session following Dr. Tanko's presentation, an audience member asked if he had considered the possibility that both atherosclerosis and bone loss are associated with a single common factor such as a cytokine cascade, or whether the bone loss might be causing atherosclerosis.

Dr. Tanko acknowledged that although he could not exclude systemic factors such as the impact of proinflammatory cytokines, he believed that his findings more clearly demonstrate the direct impact of ischemic atherosclerotic vascular disease on local bone metabolism.

He recently wrote that the underlying mechanism linking osteoporosis and cardiovascular disease is not yet fully understood, but “it seems reasonable to presume that the independent association reflects either a direct contribution of ischemic vascular disease to bone turnover or common pathomechanisms acting simultaneously on both bone and vascular cells. As for the latter option, proinflammatory cytokines such as IL-6 and TNF-α are known to exert proatherogenic effects, but they may also enhance osteoclastogenesis and consequently increased bone resorption” (J. Intern. Med. 2006;259:598–605).

Heavy calcification of the aortic wall (red arrows) at its site of bifurcation. Courtesy Dr. Laszlo B. Tanko

TORONTO — Aortic calcification was found to be an independent predictor of accelerated bone loss and hip fracture among postmenopausal women in a prospective epidemiologic study, Dr. Laszlo B. Tanko said at a world congress on osteoporosis.

Epidemiologic studies have suggested a link between cardiovascular disease and osteoporosis, two conditions that clearly are major contributors to morbidity and mortality in the elderly, but whether atherosclerosis is an independent contributor to fracture risk had not yet been determined, Dr. Tanko said. In the first long-term study addressing the questions of whether the severity and progression of aortic calcification might be associated with bone loss and fracture risk, Dr. Tanko and his colleagues from the Center for Clinical and Basic Research, Ballerup, Denmark, analyzed data from the Danish Prospective Epidemiological Risk Factors study.

In this study of 2,662 postmenopausal women, investigators identified classic cardiovascular risk factors in a baseline interview. They assessed aortic calcification using lateral x-rays and scored any calcification according to the Framingham system. Lumbar spine and total hip bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry.

A total of 1,877 patients had normal aortic calcification scores (below 3) at baseline, while 785 had scores of 3 or higher. Mean score among those in the group with lower scores was 0.4, compared with 6.5 among those in the higher-scores group.

Those with advanced aortic calcification at baseline subsequently had annual rates of progression of atherosclerotic burden that were approximately 2.5 higher than did those with normal calcification at baseline, Dr. Tanko said at the meeting, which was sponsored by the International Osteoporosis Foundation.

BMD scores at baseline for lumbar spine and hip were significantly lower among women with advanced atherosclerosis, with means of 0.84 g/cm

These differences were independent of age and body mass index, he said.

Accelerated subsequent rates of bone loss were seen among women with advanced atherosclerosis but not among those who were normal at baseline.

But at the lumbar spine, increases in BMD, rather than decreases, were seen among the advanced atherosclerosis group. An explanation for this may lie in the fact that the local blood supply to the proximal femur is unilateral, delicate, and more vulnerable to impaired blood flow than is blood supply to the vertebrae. Vertebral blood supply is bilateral and more advanced in terms of compensating for arterial obstruction, Dr. Tanko said.

During the study follow-up period, which averaged 7.5 years, there were 431 incident vertebral fractures and 37 incident hip fractures. There also were 113 acute cardiovascular events.

On multivariate regression analysis, there was a slightly increased but not statistically significant risk (relative risk 1.2) of vertebral fractures among those with advanced aortic calcification at baseline. Hip fracture risk, however, was 2.3-fold increased among those with higher calcification, compared with those whose calcification scores were normal at baseline. Regression analysis also showed that women with higher calcification also had a 2.5-fold increased risk of a cardiovascular event.

“We can say that aortic calcification is an independent predictor of accelerated bone loss and incident fracture at the hip but not at the vertebra. We are tempted to speculate that antiatherogenic measures might help decrease not only cardiovascular disease but also might help prevent fractures,” Dr. Tanko said.

In the question and answer session following Dr. Tanko's presentation, an audience member asked if he had considered the possibility that both atherosclerosis and bone loss are associated with a single common factor such as a cytokine cascade, or whether the bone loss might be causing atherosclerosis.

Dr. Tanko acknowledged that although he could not exclude systemic factors such as the impact of proinflammatory cytokines, he believed that his findings more clearly demonstrate the direct impact of ischemic atherosclerotic vascular disease on local bone metabolism.

He recently wrote that the underlying mechanism linking osteoporosis and cardiovascular disease is not yet fully understood, but “it seems reasonable to presume that the independent association reflects either a direct contribution of ischemic vascular disease to bone turnover or common pathomechanisms acting simultaneously on both bone and vascular cells. As for the latter option, proinflammatory cytokines such as IL-6 and TNF-α are known to exert proatherogenic effects, but they may also enhance osteoclastogenesis and consequently increased bone resorption” (J. Intern. Med. 2006;259:598–605).

Heavy calcification of the aortic wall (red arrows) at its site of bifurcation. Courtesy Dr. Laszlo B. Tanko

MANCHESTER, ENGLAND — A 56-year-old man, who had experienced a skin eruption 6 years earlier and received a diagnosis of early-stage mycosis fungoides, which has a good prognosis, was hospitalized following a car accident and episodes of confusion.

He died 3 weeks later of a T-cell lymphoma involving the central nervous system, Dr. Aoife Lally said at the annual meeting of the British Association of Dermatologists.

Although there have been reports of CNS involvement in mycosis fungoides, it usually occurs in the setting of advanced and histologically transformed cutaneous disease. Isolated CNS involvement in stage 1B mycosis fungoides is “remarkably rare,” said Dr. Lally of the department of dermatology, Oxford (England) Radcliffe Hospitals.

When the patient originally was examined in the dermatology department, his skin findings included annular, erythematous, scaly patches and only a few plaques. There was no scalp or nail involvement and no lymphadenopathy.

Blood count, erythrocyte sedimentation rate, and renal and hepatic profiles were all normal.

The patient did not respond to treatment with potent topical steroids, and relapsed following a course of UVB treatment. Biopsies showed folliculotropic mycosis fungoides. Treatment with photochemotherapy (PUVA) was commenced, and the patient responded well, according to Dr. Lally.

“At no point did he develop lymphadenopathy or systemic symptoms. But 5 years after initial presentation, a nodule appeared on the left ankle,” she said. This responded to radiotherapy, and the skin disease remained quiescent thereafter.

When he was admitted after the car accident, CT scan of the head revealed a frontal tumor. A craniotomy was performed, and histologic analysis confirmed the presence of a T-cell lymphoma.

“T-cell receptor gene analysis on DNA extracted from this tumor showed an identical T-cell clone to that of skin biopsies taken a year earlier,” Dr. Lally said.

Bone marrow examination was normal and staging CT found no nodal or extranodal disease.

The unusual nature of this disease course was echoed in a recent report of 10 cases of CNS involvement in mycosis fungoides. In that series, CNS involvement most commonly appeared within a few years of the initial diagnosis of mycosis fungoides, in the context of active skin disease, and with other visceral involvement (Cancer J. 2006;12:55–62). Stage at diagnosis also was significant: Only one patient had stage 1B disease, with all others having stages 2B or greater. Mean survival following the onset of CNS symptoms in this cohort was approximately 5 months.

The patient's progressive erythematous facial rash was diagnosed as early mycosis fungoides (left). CT image shows frontal T-cell lymphoma that evolved from the MF within 6 years (right). Photos courtesy Dr. Aoife Lally

MANCHESTER, ENGLAND — A 56-year-old man, who had experienced a skin eruption 6 years earlier and received a diagnosis of early-stage mycosis fungoides, which has a good prognosis, was hospitalized following a car accident and episodes of confusion.

He died 3 weeks later of a T-cell lymphoma involving the central nervous system, Dr. Aoife Lally said at the annual meeting of the British Association of Dermatologists.

Although there have been reports of CNS involvement in mycosis fungoides, it usually occurs in the setting of advanced and histologically transformed cutaneous disease. Isolated CNS involvement in stage 1B mycosis fungoides is “remarkably rare,” said Dr. Lally of the department of dermatology, Oxford (England) Radcliffe Hospitals.

When the patient originally was examined in the dermatology department, his skin findings included annular, erythematous, scaly patches and only a few plaques. There was no scalp or nail involvement and no lymphadenopathy.

Blood count, erythrocyte sedimentation rate, and renal and hepatic profiles were all normal.

The patient did not respond to treatment with potent topical steroids, and relapsed following a course of UVB treatment. Biopsies showed folliculotropic mycosis fungoides. Treatment with photochemotherapy (PUVA) was commenced, and the patient responded well, according to Dr. Lally.

“At no point did he develop lymphadenopathy or systemic symptoms. But 5 years after initial presentation, a nodule appeared on the left ankle,” she said. This responded to radiotherapy, and the skin disease remained quiescent thereafter.

When he was admitted after the car accident, CT scan of the head revealed a frontal tumor. A craniotomy was performed, and histologic analysis confirmed the presence of a T-cell lymphoma.

“T-cell receptor gene analysis on DNA extracted from this tumor showed an identical T-cell clone to that of skin biopsies taken a year earlier,” Dr. Lally said.

Bone marrow examination was normal and staging CT found no nodal or extranodal disease.

The unusual nature of this disease course was echoed in a recent report of 10 cases of CNS involvement in mycosis fungoides. In that series, CNS involvement most commonly appeared within a few years of the initial diagnosis of mycosis fungoides, in the context of active skin disease, and with other visceral involvement (Cancer J. 2006;12:55–62). Stage at diagnosis also was significant: Only one patient had stage 1B disease, with all others having stages 2B or greater. Mean survival following the onset of CNS symptoms in this cohort was approximately 5 months.

The patient's progressive erythematous facial rash was diagnosed as early mycosis fungoides (left). CT image shows frontal T-cell lymphoma that evolved from the MF within 6 years (right). Photos courtesy Dr. Aoife Lally

MANCHESTER, ENGLAND — A 56-year-old man, who had experienced a skin eruption 6 years earlier and received a diagnosis of early-stage mycosis fungoides, which has a good prognosis, was hospitalized following a car accident and episodes of confusion.

He died 3 weeks later of a T-cell lymphoma involving the central nervous system, Dr. Aoife Lally said at the annual meeting of the British Association of Dermatologists.

Although there have been reports of CNS involvement in mycosis fungoides, it usually occurs in the setting of advanced and histologically transformed cutaneous disease. Isolated CNS involvement in stage 1B mycosis fungoides is “remarkably rare,” said Dr. Lally of the department of dermatology, Oxford (England) Radcliffe Hospitals.

When the patient originally was examined in the dermatology department, his skin findings included annular, erythematous, scaly patches and only a few plaques. There was no scalp or nail involvement and no lymphadenopathy.

Blood count, erythrocyte sedimentation rate, and renal and hepatic profiles were all normal.

The patient did not respond to treatment with potent topical steroids, and relapsed following a course of UVB treatment. Biopsies showed folliculotropic mycosis fungoides. Treatment with photochemotherapy (PUVA) was commenced, and the patient responded well, according to Dr. Lally.

“At no point did he develop lymphadenopathy or systemic symptoms. But 5 years after initial presentation, a nodule appeared on the left ankle,” she said. This responded to radiotherapy, and the skin disease remained quiescent thereafter.

When he was admitted after the car accident, CT scan of the head revealed a frontal tumor. A craniotomy was performed, and histologic analysis confirmed the presence of a T-cell lymphoma.

“T-cell receptor gene analysis on DNA extracted from this tumor showed an identical T-cell clone to that of skin biopsies taken a year earlier,” Dr. Lally said.

Bone marrow examination was normal and staging CT found no nodal or extranodal disease.

The unusual nature of this disease course was echoed in a recent report of 10 cases of CNS involvement in mycosis fungoides. In that series, CNS involvement most commonly appeared within a few years of the initial diagnosis of mycosis fungoides, in the context of active skin disease, and with other visceral involvement (Cancer J. 2006;12:55–62). Stage at diagnosis also was significant: Only one patient had stage 1B disease, with all others having stages 2B or greater. Mean survival following the onset of CNS symptoms in this cohort was approximately 5 months.

The patient's progressive erythematous facial rash was diagnosed as early mycosis fungoides (left). CT image shows frontal T-cell lymphoma that evolved from the MF within 6 years (right). Photos courtesy Dr. Aoife Lally

TORONTO — Low bone mineral density in patients with adolescent idiopathic scoliosis is predictive of worsening of the spinal curvature, according to findings from a new Chinese study presented at a world congress on osteoporosis.

Previous studies have shown that adolescent idiopathic scoliosis (AIS) patients have significantly lower bone mass than do age- and sex-matched controls, but it has not previously been determined whether low bone mineral density (BMD) should be added to the list of risk factors for progression, according to Dr. V.W.Y. Hung of the department of orthopedics and traumatology, Prince of Wales Hospital, the Chinese University of Hong Kong.

In order to address this, researchers enrolled 324 girls with AIS and 276 controls aged 11-16 years in a prospective study. On recruitment, all had lumbar spine and bilateral femoral neck BMD measurements using dual energy x-ray absorptiometry (DXA), and age-adjusted z scores were calculated. Patients with scores of −1 or less were considered to have osteopenia, and progression of the spinal curvature was defined as an increase of 6 degrees on any two sequential spinal x-rays.

The hips were defined as concave and convex according to their relation to the convexity of the spine. For example, if the patient had a right thoracic curve, the right hip was defined as the convex-side hip (J. Bone Joint Surg. 2005;87:2709-16). Clinical and radiographic assessments were done every 6 months.

Mean age at diagnosis was 13.5 years, and the average initial Cobb angle was 24 degrees. The prevalence of osteopenia at the spine and hip was 27.5% and 23.1%, respectively.

Study participants were followed for a mean of 3.5 years. Data on hip BMD, which is considered more reliable than spinal BMD in adolescents, were available for 318 patients.

On logistic regression analysis, low bone mass at the concave side of the femoral neck was found to be a significant factor for scoliosis progression, with an odds ratio of 2.3, Dr. Hung said at the meeting, which was sponsored by the International Osteoporosis Foundation.

Other significant predictors were younger age and premenarcheal status at diagnosis, lower Risser grade, and a greater initial Cobb angle.

Follow-up BMD measurements done at the time skeletal maturity was reached found that low BMD persisted in 85% of AIS patients. Persistently low BMD at skeletal maturity may result in lower peak bone mass and increased risk for fractures later in life, Dr. Hung said.

“This is the first study to show that low bone mass plays an important role in predicting curve progression,” she said. While the cause of low BMD in AIS patients is unclear, some studies have suggested that inadequate calcium intake and insufficient exercise may contribute. These findings suggest that DXA screening might serve as an objective measurement to predict curve progression and might also help physicians predict risk.

TORONTO — Low bone mineral density in patients with adolescent idiopathic scoliosis is predictive of worsening of the spinal curvature, according to findings from a new Chinese study presented at a world congress on osteoporosis.

Previous studies have shown that adolescent idiopathic scoliosis (AIS) patients have significantly lower bone mass than do age- and sex-matched controls, but it has not previously been determined whether low bone mineral density (BMD) should be added to the list of risk factors for progression, according to Dr. V.W.Y. Hung of the department of orthopedics and traumatology, Prince of Wales Hospital, the Chinese University of Hong Kong.

In order to address this, researchers enrolled 324 girls with AIS and 276 controls aged 11-16 years in a prospective study. On recruitment, all had lumbar spine and bilateral femoral neck BMD measurements using dual energy x-ray absorptiometry (DXA), and age-adjusted z scores were calculated. Patients with scores of −1 or less were considered to have osteopenia, and progression of the spinal curvature was defined as an increase of 6 degrees on any two sequential spinal x-rays.

The hips were defined as concave and convex according to their relation to the convexity of the spine. For example, if the patient had a right thoracic curve, the right hip was defined as the convex-side hip (J. Bone Joint Surg. 2005;87:2709-16). Clinical and radiographic assessments were done every 6 months.

Mean age at diagnosis was 13.5 years, and the average initial Cobb angle was 24 degrees. The prevalence of osteopenia at the spine and hip was 27.5% and 23.1%, respectively.

Study participants were followed for a mean of 3.5 years. Data on hip BMD, which is considered more reliable than spinal BMD in adolescents, were available for 318 patients.

On logistic regression analysis, low bone mass at the concave side of the femoral neck was found to be a significant factor for scoliosis progression, with an odds ratio of 2.3, Dr. Hung said at the meeting, which was sponsored by the International Osteoporosis Foundation.

Other significant predictors were younger age and premenarcheal status at diagnosis, lower Risser grade, and a greater initial Cobb angle.

Follow-up BMD measurements done at the time skeletal maturity was reached found that low BMD persisted in 85% of AIS patients. Persistently low BMD at skeletal maturity may result in lower peak bone mass and increased risk for fractures later in life, Dr. Hung said.

“This is the first study to show that low bone mass plays an important role in predicting curve progression,” she said. While the cause of low BMD in AIS patients is unclear, some studies have suggested that inadequate calcium intake and insufficient exercise may contribute. These findings suggest that DXA screening might serve as an objective measurement to predict curve progression and might also help physicians predict risk.

TORONTO — Low bone mineral density in patients with adolescent idiopathic scoliosis is predictive of worsening of the spinal curvature, according to findings from a new Chinese study presented at a world congress on osteoporosis.

Previous studies have shown that adolescent idiopathic scoliosis (AIS) patients have significantly lower bone mass than do age- and sex-matched controls, but it has not previously been determined whether low bone mineral density (BMD) should be added to the list of risk factors for progression, according to Dr. V.W.Y. Hung of the department of orthopedics and traumatology, Prince of Wales Hospital, the Chinese University of Hong Kong.

In order to address this, researchers enrolled 324 girls with AIS and 276 controls aged 11-16 years in a prospective study. On recruitment, all had lumbar spine and bilateral femoral neck BMD measurements using dual energy x-ray absorptiometry (DXA), and age-adjusted z scores were calculated. Patients with scores of −1 or less were considered to have osteopenia, and progression of the spinal curvature was defined as an increase of 6 degrees on any two sequential spinal x-rays.

The hips were defined as concave and convex according to their relation to the convexity of the spine. For example, if the patient had a right thoracic curve, the right hip was defined as the convex-side hip (J. Bone Joint Surg. 2005;87:2709-16). Clinical and radiographic assessments were done every 6 months.

Mean age at diagnosis was 13.5 years, and the average initial Cobb angle was 24 degrees. The prevalence of osteopenia at the spine and hip was 27.5% and 23.1%, respectively.

Study participants were followed for a mean of 3.5 years. Data on hip BMD, which is considered more reliable than spinal BMD in adolescents, were available for 318 patients.

On logistic regression analysis, low bone mass at the concave side of the femoral neck was found to be a significant factor for scoliosis progression, with an odds ratio of 2.3, Dr. Hung said at the meeting, which was sponsored by the International Osteoporosis Foundation.

Other significant predictors were younger age and premenarcheal status at diagnosis, lower Risser grade, and a greater initial Cobb angle.

Follow-up BMD measurements done at the time skeletal maturity was reached found that low BMD persisted in 85% of AIS patients. Persistently low BMD at skeletal maturity may result in lower peak bone mass and increased risk for fractures later in life, Dr. Hung said.

“This is the first study to show that low bone mass plays an important role in predicting curve progression,” she said. While the cause of low BMD in AIS patients is unclear, some studies have suggested that inadequate calcium intake and insufficient exercise may contribute. These findings suggest that DXA screening might serve as an objective measurement to predict curve progression and might also help physicians predict risk.

MANCHESTER, ENGLAND — Reactive perforating collagenosis has been reported in a patient with severe connective tissue disease for the first time, adding to the list of underlying disorders associated with this skin eruption.

A 17-year-old female was referred with a 9-month history of a rash on the arms, shoulders, and legs. It had appeared post partum, coinciding with the onset of painful symptoms of Raynaud's phenomenon, fatigue, anergia, and pauciarticular arthritis, Dr. Anne-Marie Tobin said at the annual meeting of the British Association of Dermatologists.

The patient also had recently had a tonsillectomy for recurrent sore throat and was being tested for microcytic anemia.

The rash consisted of keratotic papules and plaques, typical of a perforating dermatosis.

An initial skin biopsy suggested a reactive folliculitis, but a repeat biopsy revealed acanthosis and an underlying perivascular infiltrate said Dr. Tobin of the department of dermatology, Waterford (Ireland) Regional Hospital. It also showed collagen entrapment in the epidermis and elimination through an epidermal depression, confirming the diagnosis of perforating collagenosis.

Because the rash worsened and the lesions became tender and unsightly, a course of 18 sessions of bath photochemotherapy (PUVA) was undertaken, she said. The cumulative dose was 20 J/cm2, and the results were excellent. Her connective tissue disease remains intractable, however. Trials of corticosteroids, mycophenolate mofetil, azathioprine, and colchicine have all been unsuccessful.

She required admission to the hospital on three occasions for infusions of iloprost to alleviate digital ischemia, but the endothelin receptor antagonist bosentan is now being used and appears to have stabilized her Raynaud's symptoms.

Recently, she was admitted because of myalgias, fatigue, elevated serum creatinine kinase, and raised serum aldolase. “The rash has also recurred, and we are awaiting resolution of the myositis to recommence bath PUVA,” Dr. Tobin said.

Other treatments that have been used successfully in reactive perforating collagenosis include UVB, allopurinol, doxycycline, and rifampin.

MANCHESTER, ENGLAND — Reactive perforating collagenosis has been reported in a patient with severe connective tissue disease for the first time, adding to the list of underlying disorders associated with this skin eruption.

A 17-year-old female was referred with a 9-month history of a rash on the arms, shoulders, and legs. It had appeared post partum, coinciding with the onset of painful symptoms of Raynaud's phenomenon, fatigue, anergia, and pauciarticular arthritis, Dr. Anne-Marie Tobin said at the annual meeting of the British Association of Dermatologists.

The patient also had recently had a tonsillectomy for recurrent sore throat and was being tested for microcytic anemia.

The rash consisted of keratotic papules and plaques, typical of a perforating dermatosis.

An initial skin biopsy suggested a reactive folliculitis, but a repeat biopsy revealed acanthosis and an underlying perivascular infiltrate said Dr. Tobin of the department of dermatology, Waterford (Ireland) Regional Hospital. It also showed collagen entrapment in the epidermis and elimination through an epidermal depression, confirming the diagnosis of perforating collagenosis.

Because the rash worsened and the lesions became tender and unsightly, a course of 18 sessions of bath photochemotherapy (PUVA) was undertaken, she said. The cumulative dose was 20 J/cm2, and the results were excellent. Her connective tissue disease remains intractable, however. Trials of corticosteroids, mycophenolate mofetil, azathioprine, and colchicine have all been unsuccessful.

She required admission to the hospital on three occasions for infusions of iloprost to alleviate digital ischemia, but the endothelin receptor antagonist bosentan is now being used and appears to have stabilized her Raynaud's symptoms.

Recently, she was admitted because of myalgias, fatigue, elevated serum creatinine kinase, and raised serum aldolase. “The rash has also recurred, and we are awaiting resolution of the myositis to recommence bath PUVA,” Dr. Tobin said.

Other treatments that have been used successfully in reactive perforating collagenosis include UVB, allopurinol, doxycycline, and rifampin.

MANCHESTER, ENGLAND — Reactive perforating collagenosis has been reported in a patient with severe connective tissue disease for the first time, adding to the list of underlying disorders associated with this skin eruption.

A 17-year-old female was referred with a 9-month history of a rash on the arms, shoulders, and legs. It had appeared post partum, coinciding with the onset of painful symptoms of Raynaud's phenomenon, fatigue, anergia, and pauciarticular arthritis, Dr. Anne-Marie Tobin said at the annual meeting of the British Association of Dermatologists.

The patient also had recently had a tonsillectomy for recurrent sore throat and was being tested for microcytic anemia.

The rash consisted of keratotic papules and plaques, typical of a perforating dermatosis.

An initial skin biopsy suggested a reactive folliculitis, but a repeat biopsy revealed acanthosis and an underlying perivascular infiltrate said Dr. Tobin of the department of dermatology, Waterford (Ireland) Regional Hospital. It also showed collagen entrapment in the epidermis and elimination through an epidermal depression, confirming the diagnosis of perforating collagenosis.

Because the rash worsened and the lesions became tender and unsightly, a course of 18 sessions of bath photochemotherapy (PUVA) was undertaken, she said. The cumulative dose was 20 J/cm2, and the results were excellent. Her connective tissue disease remains intractable, however. Trials of corticosteroids, mycophenolate mofetil, azathioprine, and colchicine have all been unsuccessful.

She required admission to the hospital on three occasions for infusions of iloprost to alleviate digital ischemia, but the endothelin receptor antagonist bosentan is now being used and appears to have stabilized her Raynaud's symptoms.

Recently, she was admitted because of myalgias, fatigue, elevated serum creatinine kinase, and raised serum aldolase. “The rash has also recurred, and we are awaiting resolution of the myositis to recommence bath PUVA,” Dr. Tobin said.

Other treatments that have been used successfully in reactive perforating collagenosis include UVB, allopurinol, doxycycline, and rifampin.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki reported at a world congress on osteoporosis.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg intravenously every 3 months. The intravenous injection takes 15-30 seconds to complete. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session; the meeting was sponsored by the International Osteoporosis Foundation.

Among patients who chose the intravenous route of administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improvements in gastrointestinal tolerance compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki reported at a world congress on osteoporosis.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg intravenously every 3 months. The intravenous injection takes 15-30 seconds to complete. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session; the meeting was sponsored by the International Osteoporosis Foundation.

Among patients who chose the intravenous route of administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improvements in gastrointestinal tolerance compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki reported at a world congress on osteoporosis.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg intravenously every 3 months. The intravenous injection takes 15-30 seconds to complete. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session; the meeting was sponsored by the International Osteoporosis Foundation.

Among patients who chose the intravenous route of administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improvements in gastrointestinal tolerance compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

TORONTO — Increased urinary excretion of a biomarker of bone resorption signals the presence and extent of bone metastases in breast cancer patients, Dr. Diana J. Leeming said at a world congress on osteoporosis.

Technetium-99 (99Tc) bone scintigraphy remains the standard method of detecting skeletal metastases in cancer patients. However, this approach is not suitable for close, frequent monitoring because of significant radiation exposure, Dr. Leeming said.

She and her colleagues previously investigated a number of biomarkers to determine if their presence correlated with the number and extent of bone metastases (Cancer Epidemiol. Biomarkers Prev. 2006;15:32-8). Among these were the resorption markers ααCTX and ββCTX; bone-specific alkaline phosphatase (a bone-formation marker); and markers of osteoclastogenesis, such as osteoprotegerin.

They determined that ααCTX—which is the nonisomerized form of the C-telopeptide of collagen type I—correlated most closely with the Soloway score quantification of bone metastases. “We have shown that, for a Soloway score of 1, indicating fewer than six metastases, ααCTX is approximately 200% increased. With a Soloway score of 3, when more than 20 metastases are present, ααCTX is elevated more than 600%,” said Dr. Leeming of Nordic Bioscience A/S, Herlev, Denmark.

The current study included 90 patients with newly diagnosed breast cancer; 45 had bone metastases verified by 99Tc scintigraphy or other imaging studies. The concentration of CTX fragments was measured in morning urine using ELISA (amyloid-β peptide enzyme-linked immunosorbent assay). There were no differences in age or body mass index between patients with and without metastases.

Mean ααCTX in patients without metastases was 0.39 mcg/mmol, a level that correlates with that seen in normal, age-matched healthy controls. For the group with metastases, however, the level was significantly higher, at 1.23 mcg/mmol, according to Dr. Leeming. Analysis also revealed that the presence of one, two, and three metastases was associated with increases of 38%, 57%, and 81% in ααCTX, respectively.

“This suggests that ααCTX may be sufficiently sensitive to detect the first bone metastasis,” she said. Histologic analysis of bone biopsy specimens using cytokeratin and tartrate-resistant acid phosphatase (TRACP) staining confirmed the localized presence of ααCTX and an increased number of osteoclasts near the tumor. The production of CTX is part of a vicious cycle, in which breast cancer cells induce RANK-L (receptor activator of nuclear factor kappa β ligand) in osteoblasts by a number of cytokines, Dr. Leeming explained. This in turn increases the number and survival of osteoclasts, and when osteoclasts resorb bone they release proteins and growth factors from the matrix, further activating cancer cells.

“This high bone remodeling could explain the release of increased levels of ααCTX,” said Dr. Leeming at the meeting, which was sponsored by the International Osteoporosis Foundation.

TORONTO — Increased urinary excretion of a biomarker of bone resorption signals the presence and extent of bone metastases in breast cancer patients, Dr. Diana J. Leeming said at a world congress on osteoporosis.

Technetium-99 (99Tc) bone scintigraphy remains the standard method of detecting skeletal metastases in cancer patients. However, this approach is not suitable for close, frequent monitoring because of significant radiation exposure, Dr. Leeming said.

She and her colleagues previously investigated a number of biomarkers to determine if their presence correlated with the number and extent of bone metastases (Cancer Epidemiol. Biomarkers Prev. 2006;15:32-8). Among these were the resorption markers ααCTX and ββCTX; bone-specific alkaline phosphatase (a bone-formation marker); and markers of osteoclastogenesis, such as osteoprotegerin.

They determined that ααCTX—which is the nonisomerized form of the C-telopeptide of collagen type I—correlated most closely with the Soloway score quantification of bone metastases. “We have shown that, for a Soloway score of 1, indicating fewer than six metastases, ααCTX is approximately 200% increased. With a Soloway score of 3, when more than 20 metastases are present, ααCTX is elevated more than 600%,” said Dr. Leeming of Nordic Bioscience A/S, Herlev, Denmark.

The current study included 90 patients with newly diagnosed breast cancer; 45 had bone metastases verified by 99Tc scintigraphy or other imaging studies. The concentration of CTX fragments was measured in morning urine using ELISA (amyloid-β peptide enzyme-linked immunosorbent assay). There were no differences in age or body mass index between patients with and without metastases.

Mean ααCTX in patients without metastases was 0.39 mcg/mmol, a level that correlates with that seen in normal, age-matched healthy controls. For the group with metastases, however, the level was significantly higher, at 1.23 mcg/mmol, according to Dr. Leeming. Analysis also revealed that the presence of one, two, and three metastases was associated with increases of 38%, 57%, and 81% in ααCTX, respectively.

“This suggests that ααCTX may be sufficiently sensitive to detect the first bone metastasis,” she said. Histologic analysis of bone biopsy specimens using cytokeratin and tartrate-resistant acid phosphatase (TRACP) staining confirmed the localized presence of ααCTX and an increased number of osteoclasts near the tumor. The production of CTX is part of a vicious cycle, in which breast cancer cells induce RANK-L (receptor activator of nuclear factor kappa β ligand) in osteoblasts by a number of cytokines, Dr. Leeming explained. This in turn increases the number and survival of osteoclasts, and when osteoclasts resorb bone they release proteins and growth factors from the matrix, further activating cancer cells.

“This high bone remodeling could explain the release of increased levels of ααCTX,” said Dr. Leeming at the meeting, which was sponsored by the International Osteoporosis Foundation.

TORONTO — Increased urinary excretion of a biomarker of bone resorption signals the presence and extent of bone metastases in breast cancer patients, Dr. Diana J. Leeming said at a world congress on osteoporosis.

Technetium-99 (99Tc) bone scintigraphy remains the standard method of detecting skeletal metastases in cancer patients. However, this approach is not suitable for close, frequent monitoring because of significant radiation exposure, Dr. Leeming said.

She and her colleagues previously investigated a number of biomarkers to determine if their presence correlated with the number and extent of bone metastases (Cancer Epidemiol. Biomarkers Prev. 2006;15:32-8). Among these were the resorption markers ααCTX and ββCTX; bone-specific alkaline phosphatase (a bone-formation marker); and markers of osteoclastogenesis, such as osteoprotegerin.

They determined that ααCTX—which is the nonisomerized form of the C-telopeptide of collagen type I—correlated most closely with the Soloway score quantification of bone metastases. “We have shown that, for a Soloway score of 1, indicating fewer than six metastases, ααCTX is approximately 200% increased. With a Soloway score of 3, when more than 20 metastases are present, ααCTX is elevated more than 600%,” said Dr. Leeming of Nordic Bioscience A/S, Herlev, Denmark.

The current study included 90 patients with newly diagnosed breast cancer; 45 had bone metastases verified by 99Tc scintigraphy or other imaging studies. The concentration of CTX fragments was measured in morning urine using ELISA (amyloid-β peptide enzyme-linked immunosorbent assay). There were no differences in age or body mass index between patients with and without metastases.

Mean ααCTX in patients without metastases was 0.39 mcg/mmol, a level that correlates with that seen in normal, age-matched healthy controls. For the group with metastases, however, the level was significantly higher, at 1.23 mcg/mmol, according to Dr. Leeming. Analysis also revealed that the presence of one, two, and three metastases was associated with increases of 38%, 57%, and 81% in ααCTX, respectively.

“This suggests that ααCTX may be sufficiently sensitive to detect the first bone metastasis,” she said. Histologic analysis of bone biopsy specimens using cytokeratin and tartrate-resistant acid phosphatase (TRACP) staining confirmed the localized presence of ααCTX and an increased number of osteoclasts near the tumor. The production of CTX is part of a vicious cycle, in which breast cancer cells induce RANK-L (receptor activator of nuclear factor kappa β ligand) in osteoblasts by a number of cytokines, Dr. Leeming explained. This in turn increases the number and survival of osteoclasts, and when osteoclasts resorb bone they release proteins and growth factors from the matrix, further activating cancer cells.

“This high bone remodeling could explain the release of increased levels of ααCTX,” said Dr. Leeming at the meeting, which was sponsored by the International Osteoporosis Foundation.

TORONTO — The extension phases of two large trials evaluating strontium ranelate for the prevention of osteoporotic fractures have shown that the efficacy previously seen at 3 years holds up during years 4 and 5, Dr. Jean-Yves Reginster said at a world congress on osteoporosis.

Efficacy of strontium ranelate was confirmed for both vertebral and nonvertebral fractures, Dr. Reginster said.

After 4 years of treatment, patients in the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial randomized to receive strontium ranelate had a significant 33% reduction in risk of new vertebral fractures compared with on placebo, said Dr. Reginster of the University of Liège, Belgium. The trial included 1,649 women with postmenopausal osteoporosis whose mean age was 69 years and whose mean lumbar spine bone mineral density T score was −3.6. They were recruited from 72 centers in 11 European countries and Australia. All had had at least one vertebral fracture.

Study patients were randomized to receive 2 g of oral strontium ranelate daily or placebo, and initially were followed for 3 years, at which time treatment was associated with a 41% risk reduction for vertebral fractures (N. Engl. J. Med. 2004;350:459-68).

In the second trial, the Treatment of Peripheral Osteoporosis (TROPOS) study, treatment with 2 g/day strontium ranelate among 5,091 postmenopausal women with osteoporosis was associated with a 16% relative risk reduction for all nonvertebral fractures at 3 years and a 39% reduction for vertebral fractures (J. Clin. Endocrinol. Metab. 2005; 90:2816-22).

At 5 years, the relative risk reduction for nonvertebral fractures was 15%, and for vertebral fractures the risk reduction was 24%.

Patients in this study were older, averaging 76.7 years, Dr. Reginster said. Mean femoral neck T score was −3.1. With regard to safety, no new concerns arose. “Among all patients at the beginning of the trials there was a slight increase in the incidence of deep vein thrombosis, but this vanished over time and was no longer apparent during years 4 and 5,” he said at the meeting, sponsored by the International Osteoporosis Foundation.

After 4 years, patients taking strontium ranelate had a significant 33% reduction in risk. DR. REGINSTER

TORONTO — The extension phases of two large trials evaluating strontium ranelate for the prevention of osteoporotic fractures have shown that the efficacy previously seen at 3 years holds up during years 4 and 5, Dr. Jean-Yves Reginster said at a world congress on osteoporosis.

Efficacy of strontium ranelate was confirmed for both vertebral and nonvertebral fractures, Dr. Reginster said.

After 4 years of treatment, patients in the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial randomized to receive strontium ranelate had a significant 33% reduction in risk of new vertebral fractures compared with on placebo, said Dr. Reginster of the University of Liège, Belgium. The trial included 1,649 women with postmenopausal osteoporosis whose mean age was 69 years and whose mean lumbar spine bone mineral density T score was −3.6. They were recruited from 72 centers in 11 European countries and Australia. All had had at least one vertebral fracture.

Study patients were randomized to receive 2 g of oral strontium ranelate daily or placebo, and initially were followed for 3 years, at which time treatment was associated with a 41% risk reduction for vertebral fractures (N. Engl. J. Med. 2004;350:459-68).

In the second trial, the Treatment of Peripheral Osteoporosis (TROPOS) study, treatment with 2 g/day strontium ranelate among 5,091 postmenopausal women with osteoporosis was associated with a 16% relative risk reduction for all nonvertebral fractures at 3 years and a 39% reduction for vertebral fractures (J. Clin. Endocrinol. Metab. 2005; 90:2816-22).

At 5 years, the relative risk reduction for nonvertebral fractures was 15%, and for vertebral fractures the risk reduction was 24%.

Patients in this study were older, averaging 76.7 years, Dr. Reginster said. Mean femoral neck T score was −3.1. With regard to safety, no new concerns arose. “Among all patients at the beginning of the trials there was a slight increase in the incidence of deep vein thrombosis, but this vanished over time and was no longer apparent during years 4 and 5,” he said at the meeting, sponsored by the International Osteoporosis Foundation.

After 4 years, patients taking strontium ranelate had a significant 33% reduction in risk. DR. REGINSTER

TORONTO — The extension phases of two large trials evaluating strontium ranelate for the prevention of osteoporotic fractures have shown that the efficacy previously seen at 3 years holds up during years 4 and 5, Dr. Jean-Yves Reginster said at a world congress on osteoporosis.

Efficacy of strontium ranelate was confirmed for both vertebral and nonvertebral fractures, Dr. Reginster said.

After 4 years of treatment, patients in the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial randomized to receive strontium ranelate had a significant 33% reduction in risk of new vertebral fractures compared with on placebo, said Dr. Reginster of the University of Liège, Belgium. The trial included 1,649 women with postmenopausal osteoporosis whose mean age was 69 years and whose mean lumbar spine bone mineral density T score was −3.6. They were recruited from 72 centers in 11 European countries and Australia. All had had at least one vertebral fracture.

Study patients were randomized to receive 2 g of oral strontium ranelate daily or placebo, and initially were followed for 3 years, at which time treatment was associated with a 41% risk reduction for vertebral fractures (N. Engl. J. Med. 2004;350:459-68).

In the second trial, the Treatment of Peripheral Osteoporosis (TROPOS) study, treatment with 2 g/day strontium ranelate among 5,091 postmenopausal women with osteoporosis was associated with a 16% relative risk reduction for all nonvertebral fractures at 3 years and a 39% reduction for vertebral fractures (J. Clin. Endocrinol. Metab. 2005; 90:2816-22).

At 5 years, the relative risk reduction for nonvertebral fractures was 15%, and for vertebral fractures the risk reduction was 24%.

Patients in this study were older, averaging 76.7 years, Dr. Reginster said. Mean femoral neck T score was −3.1. With regard to safety, no new concerns arose. “Among all patients at the beginning of the trials there was a slight increase in the incidence of deep vein thrombosis, but this vanished over time and was no longer apparent during years 4 and 5,” he said at the meeting, sponsored by the International Osteoporosis Foundation.

After 4 years, patients taking strontium ranelate had a significant 33% reduction in risk. DR. REGINSTER

AMSTERDAM — Two-year abatacept treatment of rheumatoid arthritis resulted in significant inhibition of radiographic damage in the long-term, open-label extension phase of the Abatacept in Inadequate Responders to Methotrexate trial, Dr. Harry K. Genant reported at the annual European Congress of Rheumatology.

Of the patients who completed the initial 1-year double-blind phase of the Abatacept in Inadequate responders to Methotrexate (AIM) trial, 539 were included in the extension phase. The patients received abatacept in doses of approximately 10 mg/kg every 4 weeks, plus a stable dose of methotrexate. Joint changes were evaluated as mean changes from baselines on the composite Genant-modified Sharp score, which rates the progression of joint erosions and joint space narrowing.

The mean change in total Sharp score from baseline in patients randomized to the abatacept group at year 1 was 1.07.

By year 2, the mean change was 1.55, according to Dr. Genant, who is professor emeritus, University of California, San Francisco, and chairman emeritus, Synarc Inc., San Francisco.

“Among these patients, there was less radiographic progression during the second year than during the first year. In fact, disease progression during year 2 was about 57% less than during year 1, representing an acceleration of the effectiveness of the drug,” Dr. Genant said at a press briefing unveiling the AIM trial results.

Among those patients who initially were randomized to the placebo group, the mean change from baseline in total Sharp score was 2.40 at year 1. At year 2, after having been switched to active treatment, these patients' mean Sharp score was 3.17.

The change in mean score at year 2, compared with that at year 1, was 0.46 in the abatacept group and 0.75 in the placebo group, Dr. Genant reported at the meeting.

Measures of clinical efficacy also showed durable responses during the second year of therapy, Dr. Joel M. Kremer reported in a poster session at the meeting, sponsored by the European League Against Rheumatism.

At year 1, 82% of patients who had received abatacept plus methotrexate achieved American College of Rheumatology (ACR) 20 responses, 54% achieved ACR 50 responses, and 32% achieved ACR 70 responses. The corresponding numbers at year 2 were 80%, 56%, and 34%, according to Dr. Kremer of Albany (N.Y.) Medical College.

By the completion of the long-term extension phase of the trial, participants who initially had received placebo but had been receiving abatacept for 1 year had similar clinical responses to those who had been receiving the active treatment for 2 years, with 78% achieving ACR 20 responses, and 58% and 32% achieving ACR 50 and 70 responses, respectively.

Remission, defined as a score of less than 2.6 on the Disease Activity Score (DAS 28), was reached by 25.4% of patients in the abatacept group at year 1, compared with 2.5% of those in the placebo group.

By the completion of the second year of the investigation, rates of remission were similar in the two groups, regardless of initial randomization, at 30.9% and 32.6% in the active treatment and placebo groups, respectively.

The AIM investigation initially included 652 patients from 116 centers worldwide. The results of the double-blind phase of the trial were the basis for regulatory approval of the drug in the United States, which was granted in December 2005.

Abatacept (Orencia) is a selective modulator of the CD80/CD86:CD28 costimulatory signal that is required for T-cell activation.

Dr. Genant has received consulting fees from Synarc, and Dr. Kremer has received research grants and consulting fees from Bristol-Myers Squibb.

RA progression during year 2 was less than during year 1, suggesting an acceleration of the drug's effectiveness. DR. GENANT

Courtesy Dr. Harry K Genant

An abatacept-treated patient's left hand is shown on radiography at baseline (left). The follow-up radiograph at 2 years shows moderate joint damage indicating stable, nonprogressive disease with the biologic. Photos courtesy Dr. Harry K. Genant

AMSTERDAM — Two-year abatacept treatment of rheumatoid arthritis resulted in significant inhibition of radiographic damage in the long-term, open-label extension phase of the Abatacept in Inadequate Responders to Methotrexate trial, Dr. Harry K. Genant reported at the annual European Congress of Rheumatology.

Of the patients who completed the initial 1-year double-blind phase of the Abatacept in Inadequate responders to Methotrexate (AIM) trial, 539 were included in the extension phase. The patients received abatacept in doses of approximately 10 mg/kg every 4 weeks, plus a stable dose of methotrexate. Joint changes were evaluated as mean changes from baselines on the composite Genant-modified Sharp score, which rates the progression of joint erosions and joint space narrowing.

The mean change in total Sharp score from baseline in patients randomized to the abatacept group at year 1 was 1.07.

By year 2, the mean change was 1.55, according to Dr. Genant, who is professor emeritus, University of California, San Francisco, and chairman emeritus, Synarc Inc., San Francisco.

“Among these patients, there was less radiographic progression during the second year than during the first year. In fact, disease progression during year 2 was about 57% less than during year 1, representing an acceleration of the effectiveness of the drug,” Dr. Genant said at a press briefing unveiling the AIM trial results.

Among those patients who initially were randomized to the placebo group, the mean change from baseline in total Sharp score was 2.40 at year 1. At year 2, after having been switched to active treatment, these patients' mean Sharp score was 3.17.

The change in mean score at year 2, compared with that at year 1, was 0.46 in the abatacept group and 0.75 in the placebo group, Dr. Genant reported at the meeting.

Measures of clinical efficacy also showed durable responses during the second year of therapy, Dr. Joel M. Kremer reported in a poster session at the meeting, sponsored by the European League Against Rheumatism.

At year 1, 82% of patients who had received abatacept plus methotrexate achieved American College of Rheumatology (ACR) 20 responses, 54% achieved ACR 50 responses, and 32% achieved ACR 70 responses. The corresponding numbers at year 2 were 80%, 56%, and 34%, according to Dr. Kremer of Albany (N.Y.) Medical College.

By the completion of the long-term extension phase of the trial, participants who initially had received placebo but had been receiving abatacept for 1 year had similar clinical responses to those who had been receiving the active treatment for 2 years, with 78% achieving ACR 20 responses, and 58% and 32% achieving ACR 50 and 70 responses, respectively.

Remission, defined as a score of less than 2.6 on the Disease Activity Score (DAS 28), was reached by 25.4% of patients in the abatacept group at year 1, compared with 2.5% of those in the placebo group.

By the completion of the second year of the investigation, rates of remission were similar in the two groups, regardless of initial randomization, at 30.9% and 32.6% in the active treatment and placebo groups, respectively.

The AIM investigation initially included 652 patients from 116 centers worldwide. The results of the double-blind phase of the trial were the basis for regulatory approval of the drug in the United States, which was granted in December 2005.

Abatacept (Orencia) is a selective modulator of the CD80/CD86:CD28 costimulatory signal that is required for T-cell activation.

Dr. Genant has received consulting fees from Synarc, and Dr. Kremer has received research grants and consulting fees from Bristol-Myers Squibb.

RA progression during year 2 was less than during year 1, suggesting an acceleration of the drug's effectiveness. DR. GENANT

Courtesy Dr. Harry K Genant

An abatacept-treated patient's left hand is shown on radiography at baseline (left). The follow-up radiograph at 2 years shows moderate joint damage indicating stable, nonprogressive disease with the biologic. Photos courtesy Dr. Harry K. Genant

AMSTERDAM — Two-year abatacept treatment of rheumatoid arthritis resulted in significant inhibition of radiographic damage in the long-term, open-label extension phase of the Abatacept in Inadequate Responders to Methotrexate trial, Dr. Harry K. Genant reported at the annual European Congress of Rheumatology.

Of the patients who completed the initial 1-year double-blind phase of the Abatacept in Inadequate responders to Methotrexate (AIM) trial, 539 were included in the extension phase. The patients received abatacept in doses of approximately 10 mg/kg every 4 weeks, plus a stable dose of methotrexate. Joint changes were evaluated as mean changes from baselines on the composite Genant-modified Sharp score, which rates the progression of joint erosions and joint space narrowing.

The mean change in total Sharp score from baseline in patients randomized to the abatacept group at year 1 was 1.07.

By year 2, the mean change was 1.55, according to Dr. Genant, who is professor emeritus, University of California, San Francisco, and chairman emeritus, Synarc Inc., San Francisco.

“Among these patients, there was less radiographic progression during the second year than during the first year. In fact, disease progression during year 2 was about 57% less than during year 1, representing an acceleration of the effectiveness of the drug,” Dr. Genant said at a press briefing unveiling the AIM trial results.

Among those patients who initially were randomized to the placebo group, the mean change from baseline in total Sharp score was 2.40 at year 1. At year 2, after having been switched to active treatment, these patients' mean Sharp score was 3.17.

The change in mean score at year 2, compared with that at year 1, was 0.46 in the abatacept group and 0.75 in the placebo group, Dr. Genant reported at the meeting.

Measures of clinical efficacy also showed durable responses during the second year of therapy, Dr. Joel M. Kremer reported in a poster session at the meeting, sponsored by the European League Against Rheumatism.

At year 1, 82% of patients who had received abatacept plus methotrexate achieved American College of Rheumatology (ACR) 20 responses, 54% achieved ACR 50 responses, and 32% achieved ACR 70 responses. The corresponding numbers at year 2 were 80%, 56%, and 34%, according to Dr. Kremer of Albany (N.Y.) Medical College.

By the completion of the long-term extension phase of the trial, participants who initially had received placebo but had been receiving abatacept for 1 year had similar clinical responses to those who had been receiving the active treatment for 2 years, with 78% achieving ACR 20 responses, and 58% and 32% achieving ACR 50 and 70 responses, respectively.

Remission, defined as a score of less than 2.6 on the Disease Activity Score (DAS 28), was reached by 25.4% of patients in the abatacept group at year 1, compared with 2.5% of those in the placebo group.

By the completion of the second year of the investigation, rates of remission were similar in the two groups, regardless of initial randomization, at 30.9% and 32.6% in the active treatment and placebo groups, respectively.

The AIM investigation initially included 652 patients from 116 centers worldwide. The results of the double-blind phase of the trial were the basis for regulatory approval of the drug in the United States, which was granted in December 2005.

Abatacept (Orencia) is a selective modulator of the CD80/CD86:CD28 costimulatory signal that is required for T-cell activation.

Dr. Genant has received consulting fees from Synarc, and Dr. Kremer has received research grants and consulting fees from Bristol-Myers Squibb.

RA progression during year 2 was less than during year 1, suggesting an acceleration of the drug's effectiveness. DR. GENANT

Courtesy Dr. Harry K Genant

An abatacept-treated patient's left hand is shown on radiography at baseline (left). The follow-up radiograph at 2 years shows moderate joint damage indicating stable, nonprogressive disease with the biologic. Photos courtesy Dr. Harry K. Genant

AMSTERDAM — Reassuring data on the use of etanercept in patients with juvenile idiopathic arthritis are emerging from a multicenter Spanish registry, with significant improvements being seen on all clinical parameters and no serious adverse events being reported, Dr. Inmaculada Calvo said at the annual European Congress of Rheumatology.

Etanercept was approved for the treatment of JIA in 1999, but few phase IV studies have been done evaluating the long-term safety and efficacy of tumor necrosis factor (TNF)-α blockade in these patients, noted Dr. Calvo.

A total of 103 patients have been enrolled in the registry, with follow-up extending as long as 48 months.

Fifty-three of the patients were female, the median patient age was 12.3 years, and the median age at disease onset was 5.6 years. During the 3 years prior to recruitment, 91.6% had undergone treatment with methotrexate but had shown an inadequate response, according to Dr. Calvo of the Hospital Infantil la Fe, Valencia, Spain.

All patients had polyarticular disease, 55.3% were seronegative, and 15.5% had systemic-onset disease.

At the time of analysis, 83 patients (80.6%) had been followed for at least 6 months, 72 (69.9%) had been followed for 12 months, and 49 (47.6%) had been followed for 24 months. In addition, 29 (28.2%) and 15 (14.6%) had been followed for 36 and 48 months, respectively.

No serious adverse events have been observed, and the infections reported were typical for patients of this age (see box). The median number of tender joints and swollen joints decreased from 9.09 to 0.3 and 9.24 to 3.13, respectively, Dr. Calvo wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.

Physician global assessment decreased from a median of 5.96 to 1.13, and patient global assessment fell from a median of 5.43 to 1.30. The Childhood Health Assessment Questionnaire index also decreased, from a median of 1.61 to 0.44. Laboratory parameters also improved, with the erythrocyte sedimentation rate falling from 43 to 11 mm/h and C-reactive protein level decreasing from 12 to 0.1 mg/L.

Reported Adverse Events Are Few

AMSTERDAM — Reassuring data on the use of etanercept in patients with juvenile idiopathic arthritis are emerging from a multicenter Spanish registry, with significant improvements being seen on all clinical parameters and no serious adverse events being reported, Dr. Inmaculada Calvo said at the annual European Congress of Rheumatology.

Etanercept was approved for the treatment of JIA in 1999, but few phase IV studies have been done evaluating the long-term safety and efficacy of tumor necrosis factor (TNF)-α blockade in these patients, noted Dr. Calvo.

A total of 103 patients have been enrolled in the registry, with follow-up extending as long as 48 months.

Fifty-three of the patients were female, the median patient age was 12.3 years, and the median age at disease onset was 5.6 years. During the 3 years prior to recruitment, 91.6% had undergone treatment with methotrexate but had shown an inadequate response, according to Dr. Calvo of the Hospital Infantil la Fe, Valencia, Spain.

All patients had polyarticular disease, 55.3% were seronegative, and 15.5% had systemic-onset disease.

At the time of analysis, 83 patients (80.6%) had been followed for at least 6 months, 72 (69.9%) had been followed for 12 months, and 49 (47.6%) had been followed for 24 months. In addition, 29 (28.2%) and 15 (14.6%) had been followed for 36 and 48 months, respectively.

No serious adverse events have been observed, and the infections reported were typical for patients of this age (see box). The median number of tender joints and swollen joints decreased from 9.09 to 0.3 and 9.24 to 3.13, respectively, Dr. Calvo wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.

Physician global assessment decreased from a median of 5.96 to 1.13, and patient global assessment fell from a median of 5.43 to 1.30. The Childhood Health Assessment Questionnaire index also decreased, from a median of 1.61 to 0.44. Laboratory parameters also improved, with the erythrocyte sedimentation rate falling from 43 to 11 mm/h and C-reactive protein level decreasing from 12 to 0.1 mg/L.

Reported Adverse Events Are Few

AMSTERDAM — Reassuring data on the use of etanercept in patients with juvenile idiopathic arthritis are emerging from a multicenter Spanish registry, with significant improvements being seen on all clinical parameters and no serious adverse events being reported, Dr. Inmaculada Calvo said at the annual European Congress of Rheumatology.

Etanercept was approved for the treatment of JIA in 1999, but few phase IV studies have been done evaluating the long-term safety and efficacy of tumor necrosis factor (TNF)-α blockade in these patients, noted Dr. Calvo.

A total of 103 patients have been enrolled in the registry, with follow-up extending as long as 48 months.

Fifty-three of the patients were female, the median patient age was 12.3 years, and the median age at disease onset was 5.6 years. During the 3 years prior to recruitment, 91.6% had undergone treatment with methotrexate but had shown an inadequate response, according to Dr. Calvo of the Hospital Infantil la Fe, Valencia, Spain.

All patients had polyarticular disease, 55.3% were seronegative, and 15.5% had systemic-onset disease.

At the time of analysis, 83 patients (80.6%) had been followed for at least 6 months, 72 (69.9%) had been followed for 12 months, and 49 (47.6%) had been followed for 24 months. In addition, 29 (28.2%) and 15 (14.6%) had been followed for 36 and 48 months, respectively.

No serious adverse events have been observed, and the infections reported were typical for patients of this age (see box). The median number of tender joints and swollen joints decreased from 9.09 to 0.3 and 9.24 to 3.13, respectively, Dr. Calvo wrote in a poster session at the meeting, sponsored by the European League Against Rheumatism.

Physician global assessment decreased from a median of 5.96 to 1.13, and patient global assessment fell from a median of 5.43 to 1.30. The Childhood Health Assessment Questionnaire index also decreased, from a median of 1.61 to 0.44. Laboratory parameters also improved, with the erythrocyte sedimentation rate falling from 43 to 11 mm/h and C-reactive protein level decreasing from 12 to 0.1 mg/L.

Reported Adverse Events Are Few

AMSTERDAM — Initial therapy using traditional disease-modifying antirheumatic drugs—even early, aggressively, and in combination—is inadequate for a significant proportion of patients with inflammatory arthritis, according to preliminary data from a prospective Canadian study.

In rheumatoid arthritis (RA), joint damage and the resulting disability occur during the first years of disease, and current therapeutic strategies aim to be aggressive in minimizing inflammation and preventing irreversible damage.

But among a cohort of 79 patients followed for 12 months in a real-world setting, fewer than half achieved remission with disease-modifying antirheumatic drug (DMARD) treatment, Dr. Vivian P. Bykerk said at the annual European Congress of Rheumatology.

For inclusion in the Toronto Early Arthritis Cohort, patients were required to be at least 16 years old and to have had symptoms for at least 6 weeks but less than 1 year. They had to have at least two swollen joints or one swollen metacarpophalangeal joint or proximal interphalangeal joint and to have more than one of the following characteristics: rheumatoid factor positive, anti-CCP positive, morning stiffness exceeding 45 minutes' duration, a response to nonsteroidal anti-inflammatory drugs, and a painful metatarsophalangeal joint squeeze test.

At baseline the mean patient age was 45.5 years, and 80% were female. Median duration of symptoms was 161 days.

Mean erythrocyte sedimentation rate was 28 mm/h, and mean C-reactive protein level was 13 mg/L. The mean tender joint count was 19, mean swollen joint count was 11, and mean Disease Activity Score (DAS) was 5.3. A total of 28% of patients were rheumatoid factor positive, and 67% met the criteria for RA. In addition, 26% already had erosions present in the hands or feet.

Recommended initial treatment for RA in Canada involves combination therapy, but only 60% of patients in this cohort were started on more than one DMARD. This probably reflects a lower disease burden and also possibly patient preference, said Dr. Bykerk of Mount Sinai Hospital, Toronto.

When combination therapy was used, it generally was methotrexate plus hydroxychloroquine or sulfasalazine. The methotrexate dose was 15–25 mg/week, the mean dose at 12 months was 18 mg/week, and for two-thirds of patients the dose exceeded 20 mg/week. A third of the patients opted to take their methotrexate subcutaneously, she said. “In Canada we are strong proponents of subcutaneous methotrexate in doses of 20–25 mg early on,” she said at the meeting, sponsored by the European League Against Rheumatism.

The sulfasalazine dose was 2 g/day, and the hydroxychloroquine dose was 400 mg/day.

By 12 months, only 47% of patients achieved remission as defined as a DAS28 less than 2.6, even using an aggressive DMARD strategy followed by biologic therapies in patients who were inadequate responders at 6 months.

“For a significant proportion of patients with early RA or inflammatory arthritis, a different strategy than early DMARD therapy may be required,” she said. Studies are needed to validate the earlier use of biologics and to identify prognostic factors.

AMSTERDAM — Initial therapy using traditional disease-modifying antirheumatic drugs—even early, aggressively, and in combination—is inadequate for a significant proportion of patients with inflammatory arthritis, according to preliminary data from a prospective Canadian study.

In rheumatoid arthritis (RA), joint damage and the resulting disability occur during the first years of disease, and current therapeutic strategies aim to be aggressive in minimizing inflammation and preventing irreversible damage.

But among a cohort of 79 patients followed for 12 months in a real-world setting, fewer than half achieved remission with disease-modifying antirheumatic drug (DMARD) treatment, Dr. Vivian P. Bykerk said at the annual European Congress of Rheumatology.

For inclusion in the Toronto Early Arthritis Cohort, patients were required to be at least 16 years old and to have had symptoms for at least 6 weeks but less than 1 year. They had to have at least two swollen joints or one swollen metacarpophalangeal joint or proximal interphalangeal joint and to have more than one of the following characteristics: rheumatoid factor positive, anti-CCP positive, morning stiffness exceeding 45 minutes' duration, a response to nonsteroidal anti-inflammatory drugs, and a painful metatarsophalangeal joint squeeze test.

At baseline the mean patient age was 45.5 years, and 80% were female. Median duration of symptoms was 161 days.

Mean erythrocyte sedimentation rate was 28 mm/h, and mean C-reactive protein level was 13 mg/L. The mean tender joint count was 19, mean swollen joint count was 11, and mean Disease Activity Score (DAS) was 5.3. A total of 28% of patients were rheumatoid factor positive, and 67% met the criteria for RA. In addition, 26% already had erosions present in the hands or feet.

Recommended initial treatment for RA in Canada involves combination therapy, but only 60% of patients in this cohort were started on more than one DMARD. This probably reflects a lower disease burden and also possibly patient preference, said Dr. Bykerk of Mount Sinai Hospital, Toronto.

When combination therapy was used, it generally was methotrexate plus hydroxychloroquine or sulfasalazine. The methotrexate dose was 15–25 mg/week, the mean dose at 12 months was 18 mg/week, and for two-thirds of patients the dose exceeded 20 mg/week. A third of the patients opted to take their methotrexate subcutaneously, she said. “In Canada we are strong proponents of subcutaneous methotrexate in doses of 20–25 mg early on,” she said at the meeting, sponsored by the European League Against Rheumatism.

The sulfasalazine dose was 2 g/day, and the hydroxychloroquine dose was 400 mg/day.

By 12 months, only 47% of patients achieved remission as defined as a DAS28 less than 2.6, even using an aggressive DMARD strategy followed by biologic therapies in patients who were inadequate responders at 6 months.

“For a significant proportion of patients with early RA or inflammatory arthritis, a different strategy than early DMARD therapy may be required,” she said. Studies are needed to validate the earlier use of biologics and to identify prognostic factors.

AMSTERDAM — Initial therapy using traditional disease-modifying antirheumatic drugs—even early, aggressively, and in combination—is inadequate for a significant proportion of patients with inflammatory arthritis, according to preliminary data from a prospective Canadian study.

In rheumatoid arthritis (RA), joint damage and the resulting disability occur during the first years of disease, and current therapeutic strategies aim to be aggressive in minimizing inflammation and preventing irreversible damage.

But among a cohort of 79 patients followed for 12 months in a real-world setting, fewer than half achieved remission with disease-modifying antirheumatic drug (DMARD) treatment, Dr. Vivian P. Bykerk said at the annual European Congress of Rheumatology.

For inclusion in the Toronto Early Arthritis Cohort, patients were required to be at least 16 years old and to have had symptoms for at least 6 weeks but less than 1 year. They had to have at least two swollen joints or one swollen metacarpophalangeal joint or proximal interphalangeal joint and to have more than one of the following characteristics: rheumatoid factor positive, anti-CCP positive, morning stiffness exceeding 45 minutes' duration, a response to nonsteroidal anti-inflammatory drugs, and a painful metatarsophalangeal joint squeeze test.

At baseline the mean patient age was 45.5 years, and 80% were female. Median duration of symptoms was 161 days.

Mean erythrocyte sedimentation rate was 28 mm/h, and mean C-reactive protein level was 13 mg/L. The mean tender joint count was 19, mean swollen joint count was 11, and mean Disease Activity Score (DAS) was 5.3. A total of 28% of patients were rheumatoid factor positive, and 67% met the criteria for RA. In addition, 26% already had erosions present in the hands or feet.

Recommended initial treatment for RA in Canada involves combination therapy, but only 60% of patients in this cohort were started on more than one DMARD. This probably reflects a lower disease burden and also possibly patient preference, said Dr. Bykerk of Mount Sinai Hospital, Toronto.

When combination therapy was used, it generally was methotrexate plus hydroxychloroquine or sulfasalazine. The methotrexate dose was 15–25 mg/week, the mean dose at 12 months was 18 mg/week, and for two-thirds of patients the dose exceeded 20 mg/week. A third of the patients opted to take their methotrexate subcutaneously, she said. “In Canada we are strong proponents of subcutaneous methotrexate in doses of 20–25 mg early on,” she said at the meeting, sponsored by the European League Against Rheumatism.

The sulfasalazine dose was 2 g/day, and the hydroxychloroquine dose was 400 mg/day.

By 12 months, only 47% of patients achieved remission as defined as a DAS28 less than 2.6, even using an aggressive DMARD strategy followed by biologic therapies in patients who were inadequate responders at 6 months.

“For a significant proportion of patients with early RA or inflammatory arthritis, a different strategy than early DMARD therapy may be required,” she said. Studies are needed to validate the earlier use of biologics and to identify prognostic factors.