Endocrinology

LOS ANGELES – Following 6 months of treatment with the investigational agent levoketoconazole, several clinical signs and symptoms of Cushing’s disease improved, including acne, hirsutism, and peripheral edema, as did patient-reported quality of life and symptoms of depression.

The findings come from an analysis of secondary endpoints among patients enrolled in SONICS, an open-label, phase 3 study of levoketoconazole as a treatment for endogenous Cushing’s disease (CD) that enrolled 94 patients at centers in North America, Europe and the Middle East. An investigational cortisol synthesis inhibitor, levoketoconazole is being developed by Strongbridge Biopharma and is not yet approved by the Food and Drug Administration.

“Despite the availability of approved treatments, the medical needs in Cushing’s [disease] remain very high,” the study’s principal investigator, Maria Fleseriu, MD, FACE, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists, where the data were presented. “This study demonstrates that levoketoconazole has the potential to address several clinical features of Cushing’s, owing to its clinically translated novel mechanism of action to suppress both cortisol and androgen syntheses (the latter elevated in many women with CD). Interestingly, there was no evidence of clinically important free-T reduction in men, and more studies are needed to elucidate this mechanism.”

In SONICS, adults with confirmed CD and mean 24-hour urinary free-cortisol (mUFC) value at least 1.5 times the upper limit of normal were treated with levoketoconazole in three phases: 2- to 21-week dose-titration phase (150-600 mg BID, as needed, to target mUFC normalization); 6-month maintenance phase (primary endpoint); and 6-month extended evaluation phase. The end of maintenance phase findings that focused on reductions in mUFC and safety had been previously reported. The current analysis focused on secondary endpoints, including changes from baseline to end of maintenance in investigator-assessed CD clinical signs and symptoms (acne score [range: 0-44]; hirsutism score [women only; range: 0-36]; and peripheral edema score [range: 0-12]), and patient-reported outcomes of quality of life (Cushing QoL questionnaire score [range: 0-100]) and depression (Beck Depression Inventory II score [range: 0-63]). The researchers also assessed hormones including free testosterone levels, and they used paired t-tests to infer statistical significance of the mean changes from baseline to end of maintenance for all measures.

Of the 94 patients enrolled in SONICS, 77 entered the maintenance phase, said Dr. Fleseriu, professor of medicine and neurological surgery and director of the pituitary center at Oregon Health and Science University, Portland. The patients’ mean age was 44 years and mean baseline mUFC was 243.3 mcg/day; 82% of patients were female, and 96% were white. Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295). They also observed significant mean improvements in quality of life and depression scores between baseline and end of maintenance (P less than .0001 and P = .0043, respectively). Mean free-testosterone levels increased nonsignificantly between baseline and end of maintenance in men (from 5.1 to 5.8 ng/dL) yet decreased significantly in women (from 0.3 to 0.1 ng/dL; P less than 0.0001; reference). Overall, 33 patients (35%) discontinued taking levoketoconazole by the end of the maintenance phase. Twelve (13%) discontinued because of adverse events.

“I wasn’t necessarily surprised with any of the data in this poster as I had experience with the drug in clinical trials, but I was definitely pleased to see overall significant improvements in acne score, hirsutism score in women, and peripheral edema score,” Dr. Fleseriu said. “Those are benefits that could potentially increase long-term adherence to treatment and quality-of-life improvements, particularly in women. It’s also exciting to see that quality of life and depression improved in these patients as well.”

These types of patient-reported outcomes are so important to how our patients feel about their disease and should be more of a focus for us physicians; it’s important to look at efficacy, safety and patient reported outcomes when we decide for an individualized treatment for each patient,” she noted.

Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.

[email protected]

LOS ANGELES – Following 6 months of treatment with the investigational agent levoketoconazole, several clinical signs and symptoms of Cushing’s disease improved, including acne, hirsutism, and peripheral edema, as did patient-reported quality of life and symptoms of depression.

The findings come from an analysis of secondary endpoints among patients enrolled in SONICS, an open-label, phase 3 study of levoketoconazole as a treatment for endogenous Cushing’s disease (CD) that enrolled 94 patients at centers in North America, Europe and the Middle East. An investigational cortisol synthesis inhibitor, levoketoconazole is being developed by Strongbridge Biopharma and is not yet approved by the Food and Drug Administration.

“Despite the availability of approved treatments, the medical needs in Cushing’s [disease] remain very high,” the study’s principal investigator, Maria Fleseriu, MD, FACE, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists, where the data were presented. “This study demonstrates that levoketoconazole has the potential to address several clinical features of Cushing’s, owing to its clinically translated novel mechanism of action to suppress both cortisol and androgen syntheses (the latter elevated in many women with CD). Interestingly, there was no evidence of clinically important free-T reduction in men, and more studies are needed to elucidate this mechanism.”

In SONICS, adults with confirmed CD and mean 24-hour urinary free-cortisol (mUFC) value at least 1.5 times the upper limit of normal were treated with levoketoconazole in three phases: 2- to 21-week dose-titration phase (150-600 mg BID, as needed, to target mUFC normalization); 6-month maintenance phase (primary endpoint); and 6-month extended evaluation phase. The end of maintenance phase findings that focused on reductions in mUFC and safety had been previously reported. The current analysis focused on secondary endpoints, including changes from baseline to end of maintenance in investigator-assessed CD clinical signs and symptoms (acne score [range: 0-44]; hirsutism score [women only; range: 0-36]; and peripheral edema score [range: 0-12]), and patient-reported outcomes of quality of life (Cushing QoL questionnaire score [range: 0-100]) and depression (Beck Depression Inventory II score [range: 0-63]). The researchers also assessed hormones including free testosterone levels, and they used paired t-tests to infer statistical significance of the mean changes from baseline to end of maintenance for all measures.

Of the 94 patients enrolled in SONICS, 77 entered the maintenance phase, said Dr. Fleseriu, professor of medicine and neurological surgery and director of the pituitary center at Oregon Health and Science University, Portland. The patients’ mean age was 44 years and mean baseline mUFC was 243.3 mcg/day; 82% of patients were female, and 96% were white. Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295). They also observed significant mean improvements in quality of life and depression scores between baseline and end of maintenance (P less than .0001 and P = .0043, respectively). Mean free-testosterone levels increased nonsignificantly between baseline and end of maintenance in men (from 5.1 to 5.8 ng/dL) yet decreased significantly in women (from 0.3 to 0.1 ng/dL; P less than 0.0001; reference). Overall, 33 patients (35%) discontinued taking levoketoconazole by the end of the maintenance phase. Twelve (13%) discontinued because of adverse events.

“I wasn’t necessarily surprised with any of the data in this poster as I had experience with the drug in clinical trials, but I was definitely pleased to see overall significant improvements in acne score, hirsutism score in women, and peripheral edema score,” Dr. Fleseriu said. “Those are benefits that could potentially increase long-term adherence to treatment and quality-of-life improvements, particularly in women. It’s also exciting to see that quality of life and depression improved in these patients as well.”

These types of patient-reported outcomes are so important to how our patients feel about their disease and should be more of a focus for us physicians; it’s important to look at efficacy, safety and patient reported outcomes when we decide for an individualized treatment for each patient,” she noted.

Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.

[email protected]

LOS ANGELES – Following 6 months of treatment with the investigational agent levoketoconazole, several clinical signs and symptoms of Cushing’s disease improved, including acne, hirsutism, and peripheral edema, as did patient-reported quality of life and symptoms of depression.

The findings come from an analysis of secondary endpoints among patients enrolled in SONICS, an open-label, phase 3 study of levoketoconazole as a treatment for endogenous Cushing’s disease (CD) that enrolled 94 patients at centers in North America, Europe and the Middle East. An investigational cortisol synthesis inhibitor, levoketoconazole is being developed by Strongbridge Biopharma and is not yet approved by the Food and Drug Administration.

“Despite the availability of approved treatments, the medical needs in Cushing’s [disease] remain very high,” the study’s principal investigator, Maria Fleseriu, MD, FACE, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists, where the data were presented. “This study demonstrates that levoketoconazole has the potential to address several clinical features of Cushing’s, owing to its clinically translated novel mechanism of action to suppress both cortisol and androgen syntheses (the latter elevated in many women with CD). Interestingly, there was no evidence of clinically important free-T reduction in men, and more studies are needed to elucidate this mechanism.”

In SONICS, adults with confirmed CD and mean 24-hour urinary free-cortisol (mUFC) value at least 1.5 times the upper limit of normal were treated with levoketoconazole in three phases: 2- to 21-week dose-titration phase (150-600 mg BID, as needed, to target mUFC normalization); 6-month maintenance phase (primary endpoint); and 6-month extended evaluation phase. The end of maintenance phase findings that focused on reductions in mUFC and safety had been previously reported. The current analysis focused on secondary endpoints, including changes from baseline to end of maintenance in investigator-assessed CD clinical signs and symptoms (acne score [range: 0-44]; hirsutism score [women only; range: 0-36]; and peripheral edema score [range: 0-12]), and patient-reported outcomes of quality of life (Cushing QoL questionnaire score [range: 0-100]) and depression (Beck Depression Inventory II score [range: 0-63]). The researchers also assessed hormones including free testosterone levels, and they used paired t-tests to infer statistical significance of the mean changes from baseline to end of maintenance for all measures.

Of the 94 patients enrolled in SONICS, 77 entered the maintenance phase, said Dr. Fleseriu, professor of medicine and neurological surgery and director of the pituitary center at Oregon Health and Science University, Portland. The patients’ mean age was 44 years and mean baseline mUFC was 243.3 mcg/day; 82% of patients were female, and 96% were white. Between baseline and the end of maintenance, the researchers observed significant mean improvements in acne scores (from 2.8 to –1.8, respectively; P = .0063), hirsutism scores (women only, from 7.8 to –2.6; P = .0008), and peripheral edema scores (from 1.0 to –0.4; P = .0295). They also observed significant mean improvements in quality of life and depression scores between baseline and end of maintenance (P less than .0001 and P = .0043, respectively). Mean free-testosterone levels increased nonsignificantly between baseline and end of maintenance in men (from 5.1 to 5.8 ng/dL) yet decreased significantly in women (from 0.3 to 0.1 ng/dL; P less than 0.0001; reference). Overall, 33 patients (35%) discontinued taking levoketoconazole by the end of the maintenance phase. Twelve (13%) discontinued because of adverse events.

“I wasn’t necessarily surprised with any of the data in this poster as I had experience with the drug in clinical trials, but I was definitely pleased to see overall significant improvements in acne score, hirsutism score in women, and peripheral edema score,” Dr. Fleseriu said. “Those are benefits that could potentially increase long-term adherence to treatment and quality-of-life improvements, particularly in women. It’s also exciting to see that quality of life and depression improved in these patients as well.”

These types of patient-reported outcomes are so important to how our patients feel about their disease and should be more of a focus for us physicians; it’s important to look at efficacy, safety and patient reported outcomes when we decide for an individualized treatment for each patient,” she noted.

Dr. Fleseriu reported that she has received research funding for Oregon Health and Science University from Novartis, Millendo, and Strongbridge. She has also received scientific consulting fees from Novartis and Strongbridge.

[email protected]

A treat-to-target approach using total hip T scores could help guide decisions about how long women with osteoporosis should stay on bone-building therapy, according to Serge Ferrari, MD, and his colleagues.

Using 10 years of follow-up data from 1,343 women who took denosumab in the FREEDOM trial, Dr. Ferrari and his colleagues determined that a T score of at least –2.5 would be an appropriate target for this decision.

“A T-score unit increase of 1.0 was associated with a significant reduction in fracture risk for T scores up to, but no greater than, –2.0, suggesting that a T-score threshold of at least –2.0 would be an appropriate target for therapy to maximize treatment,” said Dr. Ferrari of the University of Geneva and his colleagues. “Further improvements in bone mineral density were not associated with major additional changes in 1-year nonvertebral fracture incidence.”

The findings “highlight the importance of the relationship between hip T score and fracture risk, which is maintained during long-term therapy with denosumab. Regular monitoring of bone mineral density during therapy may be useful to determine when fracture risk has reached a minimal threshold; treatment could therefore be suspended and/or consolidated, as in the case of a reversible therapy such as denosumab.”

[email protected]

SOURCE: Ferrari S et al. J Bone Miner Res. 2019 Mar 28. doi: 10.1002/jbmr.3722.

A treat-to-target approach using total hip T scores could help guide decisions about how long women with osteoporosis should stay on bone-building therapy, according to Serge Ferrari, MD, and his colleagues.

Using 10 years of follow-up data from 1,343 women who took denosumab in the FREEDOM trial, Dr. Ferrari and his colleagues determined that a T score of at least –2.5 would be an appropriate target for this decision.

“A T-score unit increase of 1.0 was associated with a significant reduction in fracture risk for T scores up to, but no greater than, –2.0, suggesting that a T-score threshold of at least –2.0 would be an appropriate target for therapy to maximize treatment,” said Dr. Ferrari of the University of Geneva and his colleagues. “Further improvements in bone mineral density were not associated with major additional changes in 1-year nonvertebral fracture incidence.”

The findings “highlight the importance of the relationship between hip T score and fracture risk, which is maintained during long-term therapy with denosumab. Regular monitoring of bone mineral density during therapy may be useful to determine when fracture risk has reached a minimal threshold; treatment could therefore be suspended and/or consolidated, as in the case of a reversible therapy such as denosumab.”

[email protected]

SOURCE: Ferrari S et al. J Bone Miner Res. 2019 Mar 28. doi: 10.1002/jbmr.3722.

A treat-to-target approach using total hip T scores could help guide decisions about how long women with osteoporosis should stay on bone-building therapy, according to Serge Ferrari, MD, and his colleagues.

Using 10 years of follow-up data from 1,343 women who took denosumab in the FREEDOM trial, Dr. Ferrari and his colleagues determined that a T score of at least –2.5 would be an appropriate target for this decision.

“A T-score unit increase of 1.0 was associated with a significant reduction in fracture risk for T scores up to, but no greater than, –2.0, suggesting that a T-score threshold of at least –2.0 would be an appropriate target for therapy to maximize treatment,” said Dr. Ferrari of the University of Geneva and his colleagues. “Further improvements in bone mineral density were not associated with major additional changes in 1-year nonvertebral fracture incidence.”

The findings “highlight the importance of the relationship between hip T score and fracture risk, which is maintained during long-term therapy with denosumab. Regular monitoring of bone mineral density during therapy may be useful to determine when fracture risk has reached a minimal threshold; treatment could therefore be suspended and/or consolidated, as in the case of a reversible therapy such as denosumab.”

[email protected]

SOURCE: Ferrari S et al. J Bone Miner Res. 2019 Mar 28. doi: 10.1002/jbmr.3722.

Clinical question: What is the association between exposure to statin medications and histologically confirmed idiopathic inflammatory myositis?

Background: More than 200 million people worldwide use statin therapy, mostly for cardiovascular risk reduction. There is mounting evidence of an infrequent side effect known as idiopathic inflammatory myositis (IIM), that requires immunosuppressive therapy rather than just discontinuation of the medication. While there is a recently described association of statin use with an immune-mediated necrotizing myositis through the formation of an autoantibody against HMG-CoA Reductase, this epidemiological study aimed to look at the incidence of statin use against all confirmed cases of IIM.

Study design: Retrospective, population-based, case-control study.

Setting: Northwest Adelaide Health Study in Adelaide, Australia.

Synopsis: A retrospective, population-based, case-control study was conducted that compared the incidence of histologically confirmed IIM identified from the South Australian Myositis Database in patients 40 years or older with known statin exposure (n = 221) against population-based controls obtained from the North West Adelaide Health Study. The unadjusted and adjusted odds ratios and 95% confidence intervals were calculated using the conditional logistic regression analysis for the risk of statin exposure associated with IIM. There was an almost twofold (79%) increased likelihood of statin exposure in patients with IIM by comparison with controls (adjusted OR, 1.79; 95% CI, 1.23-2.60; P = .001). This study’s results indicate that patients with histologically confirmed IIM had a significantly increased likelihood of statin exposure, compared with population-based matched controls. Results were similar even when excluding necrotizing myositis, which already has a known association with statin use, which suggests that statin use could be associated with all types of IIM.

Bottom line: There was a statistically significant association between statin use and the incidence of idiopathic inflammatory myositis, which suggests that this condition is a potential serious side effect of statin therapy.

Citation: Caughey GE et al. Association of statin exposure with histologically confirmed idiopathic inflammatory myositis in an Australian population. JAMA Intern Med. 2018 Jul 30. doi: 10.1001/jamainternmed.2018.2859.

Dr. Nave is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Clinical question: What is the association between exposure to statin medications and histologically confirmed idiopathic inflammatory myositis?

Background: More than 200 million people worldwide use statin therapy, mostly for cardiovascular risk reduction. There is mounting evidence of an infrequent side effect known as idiopathic inflammatory myositis (IIM), that requires immunosuppressive therapy rather than just discontinuation of the medication. While there is a recently described association of statin use with an immune-mediated necrotizing myositis through the formation of an autoantibody against HMG-CoA Reductase, this epidemiological study aimed to look at the incidence of statin use against all confirmed cases of IIM.

Study design: Retrospective, population-based, case-control study.

Setting: Northwest Adelaide Health Study in Adelaide, Australia.

Synopsis: A retrospective, population-based, case-control study was conducted that compared the incidence of histologically confirmed IIM identified from the South Australian Myositis Database in patients 40 years or older with known statin exposure (n = 221) against population-based controls obtained from the North West Adelaide Health Study. The unadjusted and adjusted odds ratios and 95% confidence intervals were calculated using the conditional logistic regression analysis for the risk of statin exposure associated with IIM. There was an almost twofold (79%) increased likelihood of statin exposure in patients with IIM by comparison with controls (adjusted OR, 1.79; 95% CI, 1.23-2.60; P = .001). This study’s results indicate that patients with histologically confirmed IIM had a significantly increased likelihood of statin exposure, compared with population-based matched controls. Results were similar even when excluding necrotizing myositis, which already has a known association with statin use, which suggests that statin use could be associated with all types of IIM.

Bottom line: There was a statistically significant association between statin use and the incidence of idiopathic inflammatory myositis, which suggests that this condition is a potential serious side effect of statin therapy.

Citation: Caughey GE et al. Association of statin exposure with histologically confirmed idiopathic inflammatory myositis in an Australian population. JAMA Intern Med. 2018 Jul 30. doi: 10.1001/jamainternmed.2018.2859.

Dr. Nave is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Clinical question: What is the association between exposure to statin medications and histologically confirmed idiopathic inflammatory myositis?

Background: More than 200 million people worldwide use statin therapy, mostly for cardiovascular risk reduction. There is mounting evidence of an infrequent side effect known as idiopathic inflammatory myositis (IIM), that requires immunosuppressive therapy rather than just discontinuation of the medication. While there is a recently described association of statin use with an immune-mediated necrotizing myositis through the formation of an autoantibody against HMG-CoA Reductase, this epidemiological study aimed to look at the incidence of statin use against all confirmed cases of IIM.

Study design: Retrospective, population-based, case-control study.

Setting: Northwest Adelaide Health Study in Adelaide, Australia.

Synopsis: A retrospective, population-based, case-control study was conducted that compared the incidence of histologically confirmed IIM identified from the South Australian Myositis Database in patients 40 years or older with known statin exposure (n = 221) against population-based controls obtained from the North West Adelaide Health Study. The unadjusted and adjusted odds ratios and 95% confidence intervals were calculated using the conditional logistic regression analysis for the risk of statin exposure associated with IIM. There was an almost twofold (79%) increased likelihood of statin exposure in patients with IIM by comparison with controls (adjusted OR, 1.79; 95% CI, 1.23-2.60; P = .001). This study’s results indicate that patients with histologically confirmed IIM had a significantly increased likelihood of statin exposure, compared with population-based matched controls. Results were similar even when excluding necrotizing myositis, which already has a known association with statin use, which suggests that statin use could be associated with all types of IIM.

Bottom line: There was a statistically significant association between statin use and the incidence of idiopathic inflammatory myositis, which suggests that this condition is a potential serious side effect of statin therapy.

Citation: Caughey GE et al. Association of statin exposure with histologically confirmed idiopathic inflammatory myositis in an Australian population. JAMA Intern Med. 2018 Jul 30. doi: 10.1001/jamainternmed.2018.2859.

Dr. Nave is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

The Food and Drug Administration approved romosozumab-aqqg (Evenity) for treating osteoporosis in postmenopausal women who are at high risk for fracture.

“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.

The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.

The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.

Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.

[email protected]

The Food and Drug Administration approved romosozumab-aqqg (Evenity) for treating osteoporosis in postmenopausal women who are at high risk for fracture.

“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.

The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.

The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.

Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.

[email protected]

The Food and Drug Administration approved romosozumab-aqqg (Evenity) for treating osteoporosis in postmenopausal women who are at high risk for fracture.

“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.

The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.

The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.

Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.

[email protected]

NEW ORLEANS – Men taking exogenous testosterone as a short-acting nasal gel formulation saw preserved sperm counts and motility, with improved testosterone levels, according to an interim analysis of a postapproval clinical trial.

Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.

The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.

Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.

Vidyard Video

In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”

The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.

“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.

At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.

 

 

Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.

By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.

At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.

Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.

“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.

Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”

In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.

He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.

Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.

Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.

 

[email protected]

NEW ORLEANS – Men taking exogenous testosterone as a short-acting nasal gel formulation saw preserved sperm counts and motility, with improved testosterone levels, according to an interim analysis of a postapproval clinical trial.

Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.

The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.

Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.

Vidyard Video

In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”

The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.

“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.

At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.

 

 

Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.

By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.

At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.

Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.

“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.

Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”

In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.

He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.

Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.

Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.

 

[email protected]

NEW ORLEANS – Men taking exogenous testosterone as a short-acting nasal gel formulation saw preserved sperm counts and motility, with improved testosterone levels, according to an interim analysis of a postapproval clinical trial.

Testosterone nasal gel is a shorter-acting formulation of testosterone that “can mimic normal physiology,” said John Masterson, MD, a urology resident at the University of Miami. The 4.5% formulation, which was approved by the Food and Drug Administration in 2014 and is marketed as Natesto, delivers 11 mg of testosterone per dose and is dosed three times daily for testosterone replacement therapy.

The negative feedback exerted by other exogenous testosterone formulations on the hypothalamic-pituitary-gonadal (HPG) axis is known to inhibit spermatogenesis, Dr. Masterson said in a video interview at the annual meeting of the Endocrine Society.

Dr. Masterson, senior author Ranjith Ramasamy, MD, and their colleagues hypothesized that the shorter duration of action of testosterone in the nasal gel formulation would result in some conservation of gonadotropin-releasing hormone (GnRH) pulsatility, less inhibition of the HPG axis, and preservation of spermatogenesis.

Vidyard Video

In the same interview, Dr. Ramasamy, director of reproductive urology at the University of Miami, noted that “the levels of testosterone in men rise about an hour or 2 after administration [of the gel] and seem to drop off about 2 to 4 hours after the peak.” That is closer to normal physiology than other delivery systems in which “the levels of testosterone are pretty high during the day and therefore could lead to some of the side effects that we see with testosterone.”

The phase 4 prospective study enrolled 56 men aged between 18 and 55 years who had low levels of testosterone (baseline mean, 233.97 ng/dL). The mean age was 37 years.

“There are mostly younger men in our study ... and they’re usually coming in with one or two hypogonadal complaints – lack of energy, fatigue, some with erectile dysfunction,” Dr. Masterson explained in the interview. Improvement was seen in those realms, but the differences didn’t reach statistical significance, because baseline quality of life was already fairly high for these otherwise healthy men. “What we can say is that on the drug, quality of life certainly did not get worse,” he said.

At baseline, the mean luteinizing hormone (LH) level was 3.66 IU/mL, and the mean follicle stimulating hormone (FSH) level was 4.01 IU/mL.

 

 

Men were eligible to participate if they had two morning blood samples with age-adjusted low testosterone levels, and a total motile sperm count more than 5 million/ejaculation. Participants received 11-mg nasal testosterone gel three times daily for 6 months.

By 1 month into the study, 43 patients had a median testosterone level of 573 ng/dL. Fifteen patients have thus far completed all 6 months of the study and they had a median testosterone level of 604 ng/dL.

At baseline, sperm concentration was a mean 21.32 million/mL with 50% motility, and a total sperm count of 32.23 million/ejaculation. Sperm concentration at 6 months was unchanged at a median 21 million/mL.

Motility was preserved at a median 51.5% after 6 months of therapy, a statistically insignificant difference from 54% motility at baseline. Total motile sperm count decreased from a median 29.3 million/ejaculation at baseline to 19.5 million/ejaculation, a difference that didn’t reach statistical significance.

“What that means is that this nasal testosterone gel [could] be used in men who have low testosterone and are interested in preserving fertility,” said Dr. Masterson.

Dr. Ramasamy said that they’re seeing early confirmation of their initial hypothesis about the nasal gel formulation in this interim analysis. “Because it’s short acting, we believe some of the GnRH pulses and the LH and FSH that are released by the pituitary gland are still maintained, compared with the other forms of testosterone therapy, which can cause complete suppression of the [HPG] axis.”

In discussion with attendees at the poster session at which the research was featured, Dr. Masterson explained that quality-of-life measures were also collected as part of the study and will be presented separately. In addition to information about erectile function, men were asked about libido – a more complex phenomenon than erectile function alone – and early analysis showed a robust response, he said.

He acknowledged that it is not known whether craniofacial circulation facilitates testosterone transport to the brain when the nasal gel testosterone formulation is used, but that it is mechanistically plausible.

Dr. Masterson added that, practically speaking, patients should be aware that the formulation is a gel. “It sort of has to be painted on” the nasal septum within the nostrils, he said.

Aytu BioScience, which markets Natesto, partially supported the study. Dr Masterson reported no disclosures or conflicts of interest.

 

[email protected]

To the Editor: I enjoyed reading “Should metformin be used in every patient with type 2 diabetes” by Makin and Lansang in the January 2019 issue.¹

I just wanted to point out that metformin is a frequent cause of low serum vitamin B₁₂ levels, and serum vitamin B₁₂ levels should be monitored intermittently in patients using metformin.

To the Editor: I enjoyed reading “Should metformin be used in every patient with type 2 diabetes” by Makin and Lansang in the January 2019 issue.¹

I just wanted to point out that metformin is a frequent cause of low serum vitamin B₁₂ levels, and serum vitamin B₁₂ levels should be monitored intermittently in patients using metformin.

To the Editor: I enjoyed reading “Should metformin be used in every patient with type 2 diabetes” by Makin and Lansang in the January 2019 issue.¹

I just wanted to point out that metformin is a frequent cause of low serum vitamin B₁₂ levels, and serum vitamin B₁₂ levels should be monitored intermittently in patients using metformin.

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B₁₂ levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B₁₂ deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B₁₂ and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.²

The mechanism behind the development of vitamin B₁₂ deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B₁₂-intrinsic factor complex.³

Our electronic medical record has a built-in tool that suggests checking vitamin B₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.⁴

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B₁₂ levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B₁₂ deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B₁₂ and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.²

The mechanism behind the development of vitamin B₁₂ deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B₁₂-intrinsic factor complex.³

Our electronic medical record has a built-in tool that suggests checking vitamin B₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.⁴

In Reply: We thank Dr. Moskowitz for his kind comments. We agree about the need for assessing vitamin B₁₂ levels during chronic metformin use.

Secondary analysis of patients in the Diabetes Prevention Program Outcomes Study showed a higher incidence of combined low and low-normal vitamin B₁₂ deficiency in users assigned to the metformin group compared with those assigned to the placebo group at the 5-year and 13-year marks after randomization.1 Post hoc analysis of patients in the Hyperinsulinemia: the Outcome of Its Metabolic Effects trial also showed lower levels of vitamin B₁₂ and higher levels of methylmalonic acid associated with significant worsening of a validated neuropathy score in metformin users.²

The mechanism behind the development of vitamin B₁₂ deficiency is not completely understood but could possibly be alterations in intestinal mobility, bacterial overgrowth, or calcium-dependent uptake by ileal cells of the vitamin B₁₂-intrinsic factor complex.³

Our electronic medical record has a built-in tool that suggests checking vitamin B₁₂ whenever a patient requests metformin refills. There are no current guidelines on the need for baseline testing of the vitamin B₁₂ level. The American Diabetes Association recommends periodic measurement of vitamin B₁₂ levels, possibly yearly, in metformin users and more often if there are symptoms indicative of deficiency.⁴

The Food and Drug Administration has approved testosterone undecanoate (Jatenzo), an oral capsule for the treatment of male hypogonadism caused by certain conditions, such as genetic disorders or tumors that have damaged the pituitary gland.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is based on results from a 4-month clinical trial involving 166 men with hypogonadism. Patients received 237 mg testosterone undecanoate twice a day initially, a dosage that was adjusted downward or upward to a maximum of 396 mg twice a day, based on testosterone levels. At the end of the trial, 87% of men had achieved testosterone levels within the normal range.

The label for testosterone undecanoate contains a warning that the drug can cause an increase in blood pressure, raising the risk of heart attack, stroke, and cardiovascular death. Other common adverse events associated with testosterone undecanoate include headache, an increase in hematocrit, a decrease in HDL cholesterol, and nausea.

“[The] oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who, until now, have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products at the FDA’s Center for Drug Evaluation and Research, in the press release.

Testosterone undecanoate is not approved to treat age-related hypogonadism, even in cases in which men have symptoms caused by low testosterone. The drug’s benefits do not outweigh its risks in those cases, the agency noted.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved testosterone undecanoate (Jatenzo), an oral capsule for the treatment of male hypogonadism caused by certain conditions, such as genetic disorders or tumors that have damaged the pituitary gland.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is based on results from a 4-month clinical trial involving 166 men with hypogonadism. Patients received 237 mg testosterone undecanoate twice a day initially, a dosage that was adjusted downward or upward to a maximum of 396 mg twice a day, based on testosterone levels. At the end of the trial, 87% of men had achieved testosterone levels within the normal range.

The label for testosterone undecanoate contains a warning that the drug can cause an increase in blood pressure, raising the risk of heart attack, stroke, and cardiovascular death. Other common adverse events associated with testosterone undecanoate include headache, an increase in hematocrit, a decrease in HDL cholesterol, and nausea.

“[The] oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who, until now, have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products at the FDA’s Center for Drug Evaluation and Research, in the press release.

Testosterone undecanoate is not approved to treat age-related hypogonadism, even in cases in which men have symptoms caused by low testosterone. The drug’s benefits do not outweigh its risks in those cases, the agency noted.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved testosterone undecanoate (Jatenzo), an oral capsule for the treatment of male hypogonadism caused by certain conditions, such as genetic disorders or tumors that have damaged the pituitary gland.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is based on results from a 4-month clinical trial involving 166 men with hypogonadism. Patients received 237 mg testosterone undecanoate twice a day initially, a dosage that was adjusted downward or upward to a maximum of 396 mg twice a day, based on testosterone levels. At the end of the trial, 87% of men had achieved testosterone levels within the normal range.

The label for testosterone undecanoate contains a warning that the drug can cause an increase in blood pressure, raising the risk of heart attack, stroke, and cardiovascular death. Other common adverse events associated with testosterone undecanoate include headache, an increase in hematocrit, a decrease in HDL cholesterol, and nausea.

“[The] oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who, until now, have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products at the FDA’s Center for Drug Evaluation and Research, in the press release.

Testosterone undecanoate is not approved to treat age-related hypogonadism, even in cases in which men have symptoms caused by low testosterone. The drug’s benefits do not outweigh its risks in those cases, the agency noted.

Find the full press release on the FDA website.

[email protected]

NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.

“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.

The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.

“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.


The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).

The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).

In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.

However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.


Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.

Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.

He reported having no relevant financial relationships.

NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.

“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.

The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.

“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.


The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).

The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).

In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.

However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.


Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.

Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.

He reported having no relevant financial relationships.

NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.

“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.

The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.

“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.


The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).

The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).

In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.

However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.


Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.

Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.

He reported having no relevant financial relationships.

NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).

Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.

“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.

The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.

According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.

In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.

“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.

All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.

Information on enrollment is available on line: joinallofus.org.

NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).

Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.

“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.

The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.

According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.

In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.

“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.

All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.

Information on enrollment is available on line: joinallofus.org.

NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).

Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.

“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.

The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.

According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.

In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.

“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.

All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.

Information on enrollment is available on line: joinallofus.org.