Osteoporosis

Individuals with subclinical hyperthyroidism are at increased risk of hip and other fractures, according to the authors of a meta-analysis.

Researchers examined data from 70,298 individuals – 4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism – enrolled in 13 prospective cohort studies.

After adjusting for age, sex, and other fracture risk factors, the researchers found that individuals with subclinical hyperthyroidism had a 28% increase in the risk of any fracture and a 36% increased risk of hip fracture compared to individuals with normal thyroid function.

Subclinical hyperthyroidism – defined as a thyroid-stimulating hormone (TSH) level of less than 0.45 mIU/L with normal FT4 levels – was also associated with a 16% increase in the risk of nonspine fracture, according to a paper published online in the May 26 edition of JAMA.

Men with subclinical hyperthyroidism had a more than 3.5-fold increased in the risk of spine fracture, but the increase was not significant in women.

Lower TSH was associated with higher fracture rates, and the analysis showed a 61% increase in the risk of hip fracture and more than a 3.5-fold increase in spine fracture risk among individuals with a TSH less than 0.10 mIU/L.

The analysis yielded no link between subclinical hypothyroidism and fracture risk, and a comparison of fracture risk between individuals treated with thyroxine at baseline and untreated participants also showed no impact of thyroxine therapy on fracture outcomes (JAMA 2015, May 26 [doi:10.1001/jama.2015.5161].

“In prospective cohort studies, data about the association between subclinical thyroid dysfunction and fracture risk are in conflict because of inclusion of participants with overt thyroid disease and small sample sizes of participants with thyroid dysfunction or fracture events,” wrote Dr. Manuel R. Blum of Bern University Hospital, Switzerland, and an international team of coauthors.

They proposed three mechanisms by which thyroid dysfunction may affect fracture risk.

“First, thyroid hormones have been shown to have effects on osteoclasts and osteoblasts, with thyroid status in the upper normal range or excess thyroid hormones leading to accelerated bone turnover with bone loss and increased fracture risk,” they wrote.

Subclinical hyperthyroidism may also increase the risk of falls by affecting muscle strength and coordination, and thyroxine supplementation was also suggested as impacting fracture risk.

“Endogenous subclinical hyperthyroidism may be undetected for years because symptoms of subclinical hyperthyroidism are often nonspecific or absent,” the authors wrote. “This phenomenon has the potential to lead to a greater length of time for adverse associations with bone metabolism.”

The authors stressed the limitations of the observational data; for example, that thyroid function was assessed only at baseline and that some individuals may have progressed to overt thyroid dysfunction over the course of the study, and a lack of uniform definition of fracture type across the cohorts.

They said their findings supported current guideline recommendations that anyone aged 65 years or older, with subclinical hyperthyroidism and a TSH persistently lower than 0.1 mIU/L, should be treated, and treatment should be considered in those individuals with low TSH but still above 0.1 mIU/L.

The Swiss National Science Foundation and Swiss Heart Foundation supported the study. Some authors disclosed personal fees, grants and funding from a range of pharmaceutical companies.

Individuals with subclinical hyperthyroidism are at increased risk of hip and other fractures, according to the authors of a meta-analysis.

Researchers examined data from 70,298 individuals – 4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism – enrolled in 13 prospective cohort studies.

After adjusting for age, sex, and other fracture risk factors, the researchers found that individuals with subclinical hyperthyroidism had a 28% increase in the risk of any fracture and a 36% increased risk of hip fracture compared to individuals with normal thyroid function.

Subclinical hyperthyroidism – defined as a thyroid-stimulating hormone (TSH) level of less than 0.45 mIU/L with normal FT4 levels – was also associated with a 16% increase in the risk of nonspine fracture, according to a paper published online in the May 26 edition of JAMA.

Men with subclinical hyperthyroidism had a more than 3.5-fold increased in the risk of spine fracture, but the increase was not significant in women.

Lower TSH was associated with higher fracture rates, and the analysis showed a 61% increase in the risk of hip fracture and more than a 3.5-fold increase in spine fracture risk among individuals with a TSH less than 0.10 mIU/L.

The analysis yielded no link between subclinical hypothyroidism and fracture risk, and a comparison of fracture risk between individuals treated with thyroxine at baseline and untreated participants also showed no impact of thyroxine therapy on fracture outcomes (JAMA 2015, May 26 [doi:10.1001/jama.2015.5161].

“In prospective cohort studies, data about the association between subclinical thyroid dysfunction and fracture risk are in conflict because of inclusion of participants with overt thyroid disease and small sample sizes of participants with thyroid dysfunction or fracture events,” wrote Dr. Manuel R. Blum of Bern University Hospital, Switzerland, and an international team of coauthors.

They proposed three mechanisms by which thyroid dysfunction may affect fracture risk.

“First, thyroid hormones have been shown to have effects on osteoclasts and osteoblasts, with thyroid status in the upper normal range or excess thyroid hormones leading to accelerated bone turnover with bone loss and increased fracture risk,” they wrote.

Subclinical hyperthyroidism may also increase the risk of falls by affecting muscle strength and coordination, and thyroxine supplementation was also suggested as impacting fracture risk.

“Endogenous subclinical hyperthyroidism may be undetected for years because symptoms of subclinical hyperthyroidism are often nonspecific or absent,” the authors wrote. “This phenomenon has the potential to lead to a greater length of time for adverse associations with bone metabolism.”

The authors stressed the limitations of the observational data; for example, that thyroid function was assessed only at baseline and that some individuals may have progressed to overt thyroid dysfunction over the course of the study, and a lack of uniform definition of fracture type across the cohorts.

They said their findings supported current guideline recommendations that anyone aged 65 years or older, with subclinical hyperthyroidism and a TSH persistently lower than 0.1 mIU/L, should be treated, and treatment should be considered in those individuals with low TSH but still above 0.1 mIU/L.

The Swiss National Science Foundation and Swiss Heart Foundation supported the study. Some authors disclosed personal fees, grants and funding from a range of pharmaceutical companies.

Individuals with subclinical hyperthyroidism are at increased risk of hip and other fractures, according to the authors of a meta-analysis.

Researchers examined data from 70,298 individuals – 4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism – enrolled in 13 prospective cohort studies.

After adjusting for age, sex, and other fracture risk factors, the researchers found that individuals with subclinical hyperthyroidism had a 28% increase in the risk of any fracture and a 36% increased risk of hip fracture compared to individuals with normal thyroid function.

Subclinical hyperthyroidism – defined as a thyroid-stimulating hormone (TSH) level of less than 0.45 mIU/L with normal FT4 levels – was also associated with a 16% increase in the risk of nonspine fracture, according to a paper published online in the May 26 edition of JAMA.

Men with subclinical hyperthyroidism had a more than 3.5-fold increased in the risk of spine fracture, but the increase was not significant in women.

Lower TSH was associated with higher fracture rates, and the analysis showed a 61% increase in the risk of hip fracture and more than a 3.5-fold increase in spine fracture risk among individuals with a TSH less than 0.10 mIU/L.

The analysis yielded no link between subclinical hypothyroidism and fracture risk, and a comparison of fracture risk between individuals treated with thyroxine at baseline and untreated participants also showed no impact of thyroxine therapy on fracture outcomes (JAMA 2015, May 26 [doi:10.1001/jama.2015.5161].

“In prospective cohort studies, data about the association between subclinical thyroid dysfunction and fracture risk are in conflict because of inclusion of participants with overt thyroid disease and small sample sizes of participants with thyroid dysfunction or fracture events,” wrote Dr. Manuel R. Blum of Bern University Hospital, Switzerland, and an international team of coauthors.

They proposed three mechanisms by which thyroid dysfunction may affect fracture risk.

“First, thyroid hormones have been shown to have effects on osteoclasts and osteoblasts, with thyroid status in the upper normal range or excess thyroid hormones leading to accelerated bone turnover with bone loss and increased fracture risk,” they wrote.

Subclinical hyperthyroidism may also increase the risk of falls by affecting muscle strength and coordination, and thyroxine supplementation was also suggested as impacting fracture risk.

“Endogenous subclinical hyperthyroidism may be undetected for years because symptoms of subclinical hyperthyroidism are often nonspecific or absent,” the authors wrote. “This phenomenon has the potential to lead to a greater length of time for adverse associations with bone metabolism.”

The authors stressed the limitations of the observational data; for example, that thyroid function was assessed only at baseline and that some individuals may have progressed to overt thyroid dysfunction over the course of the study, and a lack of uniform definition of fracture type across the cohorts.

They said their findings supported current guideline recommendations that anyone aged 65 years or older, with subclinical hyperthyroidism and a TSH persistently lower than 0.1 mIU/L, should be treated, and treatment should be considered in those individuals with low TSH but still above 0.1 mIU/L.

The Swiss National Science Foundation and Swiss Heart Foundation supported the study. Some authors disclosed personal fees, grants and funding from a range of pharmaceutical companies.

Dual-energy x-ray absorptiometry to screen for osteoporosis is both underused in women who meet the U.S. Preventive Services Task Force criteria for screening, and overused in low-risk younger women, new data suggest.

A retrospective, longitudinal cohort study of 50,995 women attending 13 primary care clinics found that among previously unscreened women who met the criteria for screening, the 7-year cumulative incidence of DXA screening ranged from 58.8% in women aged 60-64 years with at least one risk factor, to 42.7% in women aged 75 years and older.

©iStock / ThinkStockPhotos.com

But among women who didn’t meet screening criteria, the 7-year cumulative incidence was 45.5% in women aged 50-59 years and 58.6% in women aged 60-64 years without risk factors, according to a paper published May 19 in the Journal of General Internal Medicine (doi:10.1007/s11606-015-3349-8).

The U.S. Preventive Services Task Force currently recommends screening for osteoporosis with DXA for women aged 65 and older, as well as young women at increased risk for fracture. The American Academy of Family Physicians also advised against DXA screening in women younger than age 65 without osteoporosis risk factors as part of the “Choosing Wisely” campaign.

“Additional research is needed to elucidate patient, physician, and health system barriers to evidence-based screening so that interventions can maximize the value of population screening for osteoporosis,” wrote Dr. Anna Lee D. Amarnath of the University of California, Davis Health System, and her coauthors.

The study was supported by the National Institutes of Health and the Agency for Healthcare Research and Quality. The researchers reported having no financial disclosures.

Dual-energy x-ray absorptiometry to screen for osteoporosis is both underused in women who meet the U.S. Preventive Services Task Force criteria for screening, and overused in low-risk younger women, new data suggest.

A retrospective, longitudinal cohort study of 50,995 women attending 13 primary care clinics found that among previously unscreened women who met the criteria for screening, the 7-year cumulative incidence of DXA screening ranged from 58.8% in women aged 60-64 years with at least one risk factor, to 42.7% in women aged 75 years and older.

©iStock / ThinkStockPhotos.com

But among women who didn’t meet screening criteria, the 7-year cumulative incidence was 45.5% in women aged 50-59 years and 58.6% in women aged 60-64 years without risk factors, according to a paper published May 19 in the Journal of General Internal Medicine (doi:10.1007/s11606-015-3349-8).

The U.S. Preventive Services Task Force currently recommends screening for osteoporosis with DXA for women aged 65 and older, as well as young women at increased risk for fracture. The American Academy of Family Physicians also advised against DXA screening in women younger than age 65 without osteoporosis risk factors as part of the “Choosing Wisely” campaign.

“Additional research is needed to elucidate patient, physician, and health system barriers to evidence-based screening so that interventions can maximize the value of population screening for osteoporosis,” wrote Dr. Anna Lee D. Amarnath of the University of California, Davis Health System, and her coauthors.

The study was supported by the National Institutes of Health and the Agency for Healthcare Research and Quality. The researchers reported having no financial disclosures.

Dual-energy x-ray absorptiometry to screen for osteoporosis is both underused in women who meet the U.S. Preventive Services Task Force criteria for screening, and overused in low-risk younger women, new data suggest.

A retrospective, longitudinal cohort study of 50,995 women attending 13 primary care clinics found that among previously unscreened women who met the criteria for screening, the 7-year cumulative incidence of DXA screening ranged from 58.8% in women aged 60-64 years with at least one risk factor, to 42.7% in women aged 75 years and older.

©iStock / ThinkStockPhotos.com

But among women who didn’t meet screening criteria, the 7-year cumulative incidence was 45.5% in women aged 50-59 years and 58.6% in women aged 60-64 years without risk factors, according to a paper published May 19 in the Journal of General Internal Medicine (doi:10.1007/s11606-015-3349-8).

The U.S. Preventive Services Task Force currently recommends screening for osteoporosis with DXA for women aged 65 and older, as well as young women at increased risk for fracture. The American Academy of Family Physicians also advised against DXA screening in women younger than age 65 without osteoporosis risk factors as part of the “Choosing Wisely” campaign.

“Additional research is needed to elucidate patient, physician, and health system barriers to evidence-based screening so that interventions can maximize the value of population screening for osteoporosis,” wrote Dr. Anna Lee D. Amarnath of the University of California, Davis Health System, and her coauthors.

The study was supported by the National Institutes of Health and the Agency for Healthcare Research and Quality. The researchers reported having no financial disclosures.

SEATTLE – Women with knee osteoarthritis who took bisphosphonates were 27% less likely to undergo joint replacement surgery than were women who didn’t take bisphosphonates in a U.K. cohort study of 3,928 propensity-matched users and nonusers, according to a report at the World Congress on Osteoarthritis.

“In older women with incident knee osteoarthritis, incident bisphosphonate use may be associated with lower risk of knee replacement than in nonusers,” said Dr. Tuhina Neogi of Boston University.

Dr. Neogi and her colleagues used data from The Health Improvement Network (THIN), a U.K. database of primary care patients, to identify women aged 50-89 years who received a diagnosis of knee osteoarthritis between 2003 and 2012. Patients were excluded if they were poor surgical candidates or were taking disease-modifying antirheumatic drugs, biologic agents, or other bone-active agents.

The researchers compared 1,964 women who subsequently started bisphosphonate therapy with 1,964 propensity score–matched women who did not. In 85% of the former, the bisphosphonate was alendronate, marketed as Fosamax in the United States.

During a mean follow-up of 3 years, the incidence rate of knee replacement was 21 cases per 1,000 patient-years among bisphosphonate users and 29 cases per 1,000 patient-years among nonusers, according to results reported at the meeting, which was sponsored by Osteoarthritis Research Society International.

In adjusted analyses, users had a significantly lower relative risk of undergoing this surgery (hazard ratio, 0.73), reported Dr. Neogi, who disclosed that she had no relevant conflicts of interest.

Sensitivity analyses showed an even stronger association in a separate cohort of patients matched by age, body mass index, and the duration of osteoarthritis (hazard ratio, 0.33) and a nonsignificant benefit when bisphosphonate users were instead compared against an active user group of women who initiated any other bone-modulating therapy.

“Now of course this is observational data from electronic medical records, so we cannot rule out the potential for residual bias,” she acknowledged. “Our sensitivity analyses were fairly consistent and provide some reassurance, but nonetheless, the magnitude of effect is still likely to be biased due to residual confounding.”

In an interview, Dr. Rik Lories, one of the session’s comoderators and a professor at the University of Leuven, Belgium, said that the study “is still far from practice changing. But the great thing about this research is that we are starting to split up what you would call the osteoarthritic diseases, taking osteoarthritis as the outcome [and showing] the underlying mechanisms of the different phenotypes being different.”

Dr. Neogi noted that subchrondral bone changes are prominent in knee osteoarthritis and that mechanical factors play a central role in the disease. At the same time, findings of trials of antiresorptive agents, including bisphosphonates, in knee osteoarthritis have been conflicting.

“There are a number of limitations to this study, including the fact that The Health Improvement Network does not have bone mineral density results. We tried to address this by accounting for a prior diagnosis of osteoporosis, fracture history, potential risk for fractures, body mass index, age, number of bone mineral density tests ordered, et cetera,” Dr. Neogi said. “Another limitation is that of the secular trends in use of bone-modulating agents over this time frame, and that precluded robust evaluation of the active user comparator analysis.

“Bone mineral density is still a major potential confounder here that can’t be adequately addressed,” she acknowledged.

SEATTLE – Women with knee osteoarthritis who took bisphosphonates were 27% less likely to undergo joint replacement surgery than were women who didn’t take bisphosphonates in a U.K. cohort study of 3,928 propensity-matched users and nonusers, according to a report at the World Congress on Osteoarthritis.

“In older women with incident knee osteoarthritis, incident bisphosphonate use may be associated with lower risk of knee replacement than in nonusers,” said Dr. Tuhina Neogi of Boston University.

Dr. Neogi and her colleagues used data from The Health Improvement Network (THIN), a U.K. database of primary care patients, to identify women aged 50-89 years who received a diagnosis of knee osteoarthritis between 2003 and 2012. Patients were excluded if they were poor surgical candidates or were taking disease-modifying antirheumatic drugs, biologic agents, or other bone-active agents.

The researchers compared 1,964 women who subsequently started bisphosphonate therapy with 1,964 propensity score–matched women who did not. In 85% of the former, the bisphosphonate was alendronate, marketed as Fosamax in the United States.

During a mean follow-up of 3 years, the incidence rate of knee replacement was 21 cases per 1,000 patient-years among bisphosphonate users and 29 cases per 1,000 patient-years among nonusers, according to results reported at the meeting, which was sponsored by Osteoarthritis Research Society International.

In adjusted analyses, users had a significantly lower relative risk of undergoing this surgery (hazard ratio, 0.73), reported Dr. Neogi, who disclosed that she had no relevant conflicts of interest.

Sensitivity analyses showed an even stronger association in a separate cohort of patients matched by age, body mass index, and the duration of osteoarthritis (hazard ratio, 0.33) and a nonsignificant benefit when bisphosphonate users were instead compared against an active user group of women who initiated any other bone-modulating therapy.

“Now of course this is observational data from electronic medical records, so we cannot rule out the potential for residual bias,” she acknowledged. “Our sensitivity analyses were fairly consistent and provide some reassurance, but nonetheless, the magnitude of effect is still likely to be biased due to residual confounding.”

In an interview, Dr. Rik Lories, one of the session’s comoderators and a professor at the University of Leuven, Belgium, said that the study “is still far from practice changing. But the great thing about this research is that we are starting to split up what you would call the osteoarthritic diseases, taking osteoarthritis as the outcome [and showing] the underlying mechanisms of the different phenotypes being different.”

Dr. Neogi noted that subchrondral bone changes are prominent in knee osteoarthritis and that mechanical factors play a central role in the disease. At the same time, findings of trials of antiresorptive agents, including bisphosphonates, in knee osteoarthritis have been conflicting.

“There are a number of limitations to this study, including the fact that The Health Improvement Network does not have bone mineral density results. We tried to address this by accounting for a prior diagnosis of osteoporosis, fracture history, potential risk for fractures, body mass index, age, number of bone mineral density tests ordered, et cetera,” Dr. Neogi said. “Another limitation is that of the secular trends in use of bone-modulating agents over this time frame, and that precluded robust evaluation of the active user comparator analysis.

“Bone mineral density is still a major potential confounder here that can’t be adequately addressed,” she acknowledged.

SEATTLE – Women with knee osteoarthritis who took bisphosphonates were 27% less likely to undergo joint replacement surgery than were women who didn’t take bisphosphonates in a U.K. cohort study of 3,928 propensity-matched users and nonusers, according to a report at the World Congress on Osteoarthritis.

“In older women with incident knee osteoarthritis, incident bisphosphonate use may be associated with lower risk of knee replacement than in nonusers,” said Dr. Tuhina Neogi of Boston University.

Dr. Neogi and her colleagues used data from The Health Improvement Network (THIN), a U.K. database of primary care patients, to identify women aged 50-89 years who received a diagnosis of knee osteoarthritis between 2003 and 2012. Patients were excluded if they were poor surgical candidates or were taking disease-modifying antirheumatic drugs, biologic agents, or other bone-active agents.

The researchers compared 1,964 women who subsequently started bisphosphonate therapy with 1,964 propensity score–matched women who did not. In 85% of the former, the bisphosphonate was alendronate, marketed as Fosamax in the United States.

During a mean follow-up of 3 years, the incidence rate of knee replacement was 21 cases per 1,000 patient-years among bisphosphonate users and 29 cases per 1,000 patient-years among nonusers, according to results reported at the meeting, which was sponsored by Osteoarthritis Research Society International.

In adjusted analyses, users had a significantly lower relative risk of undergoing this surgery (hazard ratio, 0.73), reported Dr. Neogi, who disclosed that she had no relevant conflicts of interest.

Sensitivity analyses showed an even stronger association in a separate cohort of patients matched by age, body mass index, and the duration of osteoarthritis (hazard ratio, 0.33) and a nonsignificant benefit when bisphosphonate users were instead compared against an active user group of women who initiated any other bone-modulating therapy.

“Now of course this is observational data from electronic medical records, so we cannot rule out the potential for residual bias,” she acknowledged. “Our sensitivity analyses were fairly consistent and provide some reassurance, but nonetheless, the magnitude of effect is still likely to be biased due to residual confounding.”

In an interview, Dr. Rik Lories, one of the session’s comoderators and a professor at the University of Leuven, Belgium, said that the study “is still far from practice changing. But the great thing about this research is that we are starting to split up what you would call the osteoarthritic diseases, taking osteoarthritis as the outcome [and showing] the underlying mechanisms of the different phenotypes being different.”

Dr. Neogi noted that subchrondral bone changes are prominent in knee osteoarthritis and that mechanical factors play a central role in the disease. At the same time, findings of trials of antiresorptive agents, including bisphosphonates, in knee osteoarthritis have been conflicting.

“There are a number of limitations to this study, including the fact that The Health Improvement Network does not have bone mineral density results. We tried to address this by accounting for a prior diagnosis of osteoporosis, fracture history, potential risk for fractures, body mass index, age, number of bone mineral density tests ordered, et cetera,” Dr. Neogi said. “Another limitation is that of the secular trends in use of bone-modulating agents over this time frame, and that precluded robust evaluation of the active user comparator analysis.

“Bone mineral density is still a major potential confounder here that can’t be adequately addressed,” she acknowledged.

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

Hip replacement is becoming more common among middle-aged Americans at the same time as the number of surgeons who perform the procedure is declining, Dr. Alexander S. McLawhorn said at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In 2011, patients aged 45-64 years underwent 42.3% of the hip replacements performed, compared with 33.9% in 2002. The number of replacements performed rose from approximately 68,000 in 2002 to 128,000 in 2011, an increase of 89.2%, compared with an increase of 37.0% among those aged 65 years and older, according to data from the Nationwide Inpatient Sample.

This “observed growth was best explained by an expansion of the middle-aged population in the United States. This particular age group is projected to continue expanding, and as such the demand for [hip replacement] in this active group of patients will likely continue to rise as well,” Dr. McLawhorn of the Hospital for Special Surgery, New York, said in a written statement.

According to membership data from the AAOS, however, the number of physicians performing hip replacements declined by almost 29% from 2002 to 2011, which will “increase the future revision burden” on those surgeons who are still doing the procedure, the investigators said.

Dr. McLawhorn had no conflicts to report, but one of his associates disclosed relationships with Ethicon, the Knee Society, Medtronic, Mekanika, and Zimmer.

[email protected]

Hip replacement is becoming more common among middle-aged Americans at the same time as the number of surgeons who perform the procedure is declining, Dr. Alexander S. McLawhorn said at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In 2011, patients aged 45-64 years underwent 42.3% of the hip replacements performed, compared with 33.9% in 2002. The number of replacements performed rose from approximately 68,000 in 2002 to 128,000 in 2011, an increase of 89.2%, compared with an increase of 37.0% among those aged 65 years and older, according to data from the Nationwide Inpatient Sample.

This “observed growth was best explained by an expansion of the middle-aged population in the United States. This particular age group is projected to continue expanding, and as such the demand for [hip replacement] in this active group of patients will likely continue to rise as well,” Dr. McLawhorn of the Hospital for Special Surgery, New York, said in a written statement.

According to membership data from the AAOS, however, the number of physicians performing hip replacements declined by almost 29% from 2002 to 2011, which will “increase the future revision burden” on those surgeons who are still doing the procedure, the investigators said.

Dr. McLawhorn had no conflicts to report, but one of his associates disclosed relationships with Ethicon, the Knee Society, Medtronic, Mekanika, and Zimmer.

[email protected]

Hip replacement is becoming more common among middle-aged Americans at the same time as the number of surgeons who perform the procedure is declining, Dr. Alexander S. McLawhorn said at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In 2011, patients aged 45-64 years underwent 42.3% of the hip replacements performed, compared with 33.9% in 2002. The number of replacements performed rose from approximately 68,000 in 2002 to 128,000 in 2011, an increase of 89.2%, compared with an increase of 37.0% among those aged 65 years and older, according to data from the Nationwide Inpatient Sample.

This “observed growth was best explained by an expansion of the middle-aged population in the United States. This particular age group is projected to continue expanding, and as such the demand for [hip replacement] in this active group of patients will likely continue to rise as well,” Dr. McLawhorn of the Hospital for Special Surgery, New York, said in a written statement.

According to membership data from the AAOS, however, the number of physicians performing hip replacements declined by almost 29% from 2002 to 2011, which will “increase the future revision burden” on those surgeons who are still doing the procedure, the investigators said.

Dr. McLawhorn had no conflicts to report, but one of his associates disclosed relationships with Ethicon, the Knee Society, Medtronic, Mekanika, and Zimmer.

[email protected]

Giving bone-strengthening medication routinely to all elderly women who sustain a wrist fracture would reduce subsequent hip fractures by about a quarter, but at a cost of over $200,000 per prevented fracture. Additionally, expanded bisphosphonate use could cause nearly 20,000 more atypical femur fractures in this population.

Dr. Suneel Bhat and his associates at Thomas Jefferson University, Philadelphia, used sophisticated modeling techniques to project costs and consequences of wider prescribing of bisphosphonates for bone fragility in women aged 65 years and older. Distal radius fracture is known to be associated with osteoporosis in women of this age, who are then at increased risk of subsequent fracture. Dr. Bhat presented his findings on March 24 at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

Study authors drew from the medical literature and publicly available Medicare data to obtain fracture incidence data and cost information for statistical modeling. Bhat and colleagues obtained age-specific incidence of distal radius fractures among women aged 65 and older, as well as rates of hip fracture following wrist fractures, both for those who did and did not receive the bisphosphonate risendronate. Atypical femur fracture is a known complication of bisphosphonate treatment for some patients; the risk of this complication and medication costs were drawn from the literature.

To assess the direct costs of hip fracture treatment, investigators used Medicare reimbursement data to price treatment components, including inpatient care as well as surgical and anesthesia services.

From these data, investigators used a modified Monte Carlo technique to obtain a cost and incidence model. This model predicted that 357,656 lifetime subsequent hip fractures would occur in elderly women with wrist fracture; this number would drop to 262,767 with universal bisphosphonate treatment. The cost for this savings, an aggregate $19.5 billion in drug costs, meant that each fracture prevented would cost $205,534. An additional 19,464 patients would sustain atypical femur fracture from risendronate treatment.

Average risendronate costs were estimated at $1,485/patient-year. This figure would have to fall to just $70/patient yearly to make risendronate treatment cost effective, Dr. Bhat calculated.

Giving bone-strengthening medication routinely to all elderly women who sustain a wrist fracture would reduce subsequent hip fractures by about a quarter, but at a cost of over $200,000 per prevented fracture. Additionally, expanded bisphosphonate use could cause nearly 20,000 more atypical femur fractures in this population.

Dr. Suneel Bhat and his associates at Thomas Jefferson University, Philadelphia, used sophisticated modeling techniques to project costs and consequences of wider prescribing of bisphosphonates for bone fragility in women aged 65 years and older. Distal radius fracture is known to be associated with osteoporosis in women of this age, who are then at increased risk of subsequent fracture. Dr. Bhat presented his findings on March 24 at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

Study authors drew from the medical literature and publicly available Medicare data to obtain fracture incidence data and cost information for statistical modeling. Bhat and colleagues obtained age-specific incidence of distal radius fractures among women aged 65 and older, as well as rates of hip fracture following wrist fractures, both for those who did and did not receive the bisphosphonate risendronate. Atypical femur fracture is a known complication of bisphosphonate treatment for some patients; the risk of this complication and medication costs were drawn from the literature.

To assess the direct costs of hip fracture treatment, investigators used Medicare reimbursement data to price treatment components, including inpatient care as well as surgical and anesthesia services.

From these data, investigators used a modified Monte Carlo technique to obtain a cost and incidence model. This model predicted that 357,656 lifetime subsequent hip fractures would occur in elderly women with wrist fracture; this number would drop to 262,767 with universal bisphosphonate treatment. The cost for this savings, an aggregate $19.5 billion in drug costs, meant that each fracture prevented would cost $205,534. An additional 19,464 patients would sustain atypical femur fracture from risendronate treatment.

Average risendronate costs were estimated at $1,485/patient-year. This figure would have to fall to just $70/patient yearly to make risendronate treatment cost effective, Dr. Bhat calculated.

Giving bone-strengthening medication routinely to all elderly women who sustain a wrist fracture would reduce subsequent hip fractures by about a quarter, but at a cost of over $200,000 per prevented fracture. Additionally, expanded bisphosphonate use could cause nearly 20,000 more atypical femur fractures in this population.

Dr. Suneel Bhat and his associates at Thomas Jefferson University, Philadelphia, used sophisticated modeling techniques to project costs and consequences of wider prescribing of bisphosphonates for bone fragility in women aged 65 years and older. Distal radius fracture is known to be associated with osteoporosis in women of this age, who are then at increased risk of subsequent fracture. Dr. Bhat presented his findings on March 24 at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

Study authors drew from the medical literature and publicly available Medicare data to obtain fracture incidence data and cost information for statistical modeling. Bhat and colleagues obtained age-specific incidence of distal radius fractures among women aged 65 and older, as well as rates of hip fracture following wrist fractures, both for those who did and did not receive the bisphosphonate risendronate. Atypical femur fracture is a known complication of bisphosphonate treatment for some patients; the risk of this complication and medication costs were drawn from the literature.

To assess the direct costs of hip fracture treatment, investigators used Medicare reimbursement data to price treatment components, including inpatient care as well as surgical and anesthesia services.

From these data, investigators used a modified Monte Carlo technique to obtain a cost and incidence model. This model predicted that 357,656 lifetime subsequent hip fractures would occur in elderly women with wrist fracture; this number would drop to 262,767 with universal bisphosphonate treatment. The cost for this savings, an aggregate $19.5 billion in drug costs, meant that each fracture prevented would cost $205,534. An additional 19,464 patients would sustain atypical femur fracture from risendronate treatment.

Average risendronate costs were estimated at $1,485/patient-year. This figure would have to fall to just $70/patient yearly to make risendronate treatment cost effective, Dr. Bhat calculated.

A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.

Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).

Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.

This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).

“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.

Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.

A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.

Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).

Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.

This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).

“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.

Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.

A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.

Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).

Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.

This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).

“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.

Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.

HOUSTON – The risk of adverse events may be cumulative over the lifetime of patients taking oral corticosteroids for urticaria.

Dr. Dennis Ledford, professor of medicine at the University of South Florida, Tampa, and his colleagues examined records of 12,647 patients culled from a commercial claims database between January 2008 and December 2012 who had taken oral corticosteroids for chronic idiopathic or spontaneous urticaria during a 12-month period. More than half (55%) used oral corticosteroids (mean dosage of 367.5 mg) for an average of 16.2 days. At follow-up, patients displayed adverse events at a rate of 27 per 100 patient-years.

Deepak Chitnis/Frontline Medical News

Adverse events mostly included skeletal conditions such as osteoporosis and bone fractures, but investigators also noted diabetes, hypertension, lipid disorders, depression, mania, and cataracts, Dr. Ledford said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

More concerning, “there’s a cumulative risk,” Dr. Ledford said in an interview. “The more [prednisone equivalent] you take over your lifetime, the greater the chance is that you’re going to develop the side effects we’ve listed here.”

Using time-sensitive Cox regression models, Dr. Ledford and his colleagues determined that the risk for adverse events went up by 7% for each gram dose of prednisone equivalent to which patients were exposed after adjusting for age, sex, immunomodulator use, and Charlson Comorbidity Index. Only cataracts were not subject to the cumulative effects.

“The message of this fairly large analysis is that there are cumulative side effects to prednisone that may not be evident to the physician or clinician performing day-to-day care of patients,” Dr. Ledford said. “These effects are slow to develop and often present in areas of medicine that the physician treating urticaria would not take care of.”

Patients enrolled in this study had all been diagnosed with urticaria at either of two outpatient clinic visits at least 6 weeks apart in a single calendar year, or had received one diagnosis of urticaria and one of angioedema at two separate outpatient clinics at least 6 weeks apart. Patients were followed for at least 1 year after completion of the initial 12-month study period, until end of enrollment or end of study.

Dr. Ledford stressed the need to use noncorticosteroid therapies when treating chronic urticaria, such as calcineurin inhibitors – which also carry risks of hypertension and cancer – or omalizumab.

The study was funded by Genentech and Novartis Pharma AG which market omalizumab as Xolair. Dr. Ledford disclosed that he is affiliated with Genentech, Novartis Pharma AG, and a number of other pharmaceutical companies.

[email protected] 


HOUSTON – The risk of adverse events may be cumulative over the lifetime of patients taking oral corticosteroids for urticaria.

Dr. Dennis Ledford, professor of medicine at the University of South Florida, Tampa, and his colleagues examined records of 12,647 patients culled from a commercial claims database between January 2008 and December 2012 who had taken oral corticosteroids for chronic idiopathic or spontaneous urticaria during a 12-month period. More than half (55%) used oral corticosteroids (mean dosage of 367.5 mg) for an average of 16.2 days. At follow-up, patients displayed adverse events at a rate of 27 per 100 patient-years.

Deepak Chitnis/Frontline Medical News

Adverse events mostly included skeletal conditions such as osteoporosis and bone fractures, but investigators also noted diabetes, hypertension, lipid disorders, depression, mania, and cataracts, Dr. Ledford said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

More concerning, “there’s a cumulative risk,” Dr. Ledford said in an interview. “The more [prednisone equivalent] you take over your lifetime, the greater the chance is that you’re going to develop the side effects we’ve listed here.”

Using time-sensitive Cox regression models, Dr. Ledford and his colleagues determined that the risk for adverse events went up by 7% for each gram dose of prednisone equivalent to which patients were exposed after adjusting for age, sex, immunomodulator use, and Charlson Comorbidity Index. Only cataracts were not subject to the cumulative effects.

“The message of this fairly large analysis is that there are cumulative side effects to prednisone that may not be evident to the physician or clinician performing day-to-day care of patients,” Dr. Ledford said. “These effects are slow to develop and often present in areas of medicine that the physician treating urticaria would not take care of.”

Patients enrolled in this study had all been diagnosed with urticaria at either of two outpatient clinic visits at least 6 weeks apart in a single calendar year, or had received one diagnosis of urticaria and one of angioedema at two separate outpatient clinics at least 6 weeks apart. Patients were followed for at least 1 year after completion of the initial 12-month study period, until end of enrollment or end of study.

Dr. Ledford stressed the need to use noncorticosteroid therapies when treating chronic urticaria, such as calcineurin inhibitors – which also carry risks of hypertension and cancer – or omalizumab.

The study was funded by Genentech and Novartis Pharma AG which market omalizumab as Xolair. Dr. Ledford disclosed that he is affiliated with Genentech, Novartis Pharma AG, and a number of other pharmaceutical companies.

[email protected] 


HOUSTON – The risk of adverse events may be cumulative over the lifetime of patients taking oral corticosteroids for urticaria.

Dr. Dennis Ledford, professor of medicine at the University of South Florida, Tampa, and his colleagues examined records of 12,647 patients culled from a commercial claims database between January 2008 and December 2012 who had taken oral corticosteroids for chronic idiopathic or spontaneous urticaria during a 12-month period. More than half (55%) used oral corticosteroids (mean dosage of 367.5 mg) for an average of 16.2 days. At follow-up, patients displayed adverse events at a rate of 27 per 100 patient-years.

Deepak Chitnis/Frontline Medical News

Adverse events mostly included skeletal conditions such as osteoporosis and bone fractures, but investigators also noted diabetes, hypertension, lipid disorders, depression, mania, and cataracts, Dr. Ledford said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

More concerning, “there’s a cumulative risk,” Dr. Ledford said in an interview. “The more [prednisone equivalent] you take over your lifetime, the greater the chance is that you’re going to develop the side effects we’ve listed here.”

Using time-sensitive Cox regression models, Dr. Ledford and his colleagues determined that the risk for adverse events went up by 7% for each gram dose of prednisone equivalent to which patients were exposed after adjusting for age, sex, immunomodulator use, and Charlson Comorbidity Index. Only cataracts were not subject to the cumulative effects.

“The message of this fairly large analysis is that there are cumulative side effects to prednisone that may not be evident to the physician or clinician performing day-to-day care of patients,” Dr. Ledford said. “These effects are slow to develop and often present in areas of medicine that the physician treating urticaria would not take care of.”

Patients enrolled in this study had all been diagnosed with urticaria at either of two outpatient clinic visits at least 6 weeks apart in a single calendar year, or had received one diagnosis of urticaria and one of angioedema at two separate outpatient clinics at least 6 weeks apart. Patients were followed for at least 1 year after completion of the initial 12-month study period, until end of enrollment or end of study.

Dr. Ledford stressed the need to use noncorticosteroid therapies when treating chronic urticaria, such as calcineurin inhibitors – which also carry risks of hypertension and cancer – or omalizumab.

The study was funded by Genentech and Novartis Pharma AG which market omalizumab as Xolair. Dr. Ledford disclosed that he is affiliated with Genentech, Novartis Pharma AG, and a number of other pharmaceutical companies.

[email protected] 


Eczema in adulthood is directly associated with an increase in incidence of injuries that cause physical limitations, particularly fracture, bone, and joint injuries, according to the results of a prospective study published online in JAMA Dermatology.

“The risk of bone fracture and other injury causing limitation in adults with eczema has been largely unexplored,” noted Dr. Nitin Garg and Dr. Jonathan I. Silverberg of Northwestern University in Chicago.

“Patients with eczema may be at risk of fracture given their use of systemic corticosteroids, which may decrease bone mineral density [and] therefore, studies describing the prevalence of fracture among adults with eczema are needed,” they added (JAMA Dermatol. 2015;151:33-41 [doi:10.1001/jamadermatol.2014.2098]).

©aniaostudio/Thinkstock.com

Dr. Garg and Dr. Silverberg used data from the 2012 National Health Interview Survey, which was conducted by the National Center for Health Statistics, to create their prospective, questionnaire-based study. The final analysis included 34,500 adults aged 18-85 years. They controlled for factors such as age, sex, race, Hispanic origin, household income, highest level of household education, family structure, and whether or not the subject was born in the United States.

The prevalence of self-reported eczema or skin allergy was 7.2%, the prevalence of any limitation-causing injury was 2.0%, and any limitation-causing injury in the past 12 months among adults was 7.2%. A fracture and bone or joint injury (FBJI) causing limitation was reported by 1.5% of the study population and other types of injury causing limitation were reported by 0.6%. The prevalence of FBJI causing limitation increased gradually with age, to peak in subjects aged 50-69 years, decreasing thereafter.

In a logistic regression analysis, adults with eczema had a 44% increased risk of any injury causing limitation (adjusted odds ratio, 1.44), and a 67% increased risk of FBJI (aOR, 1.67).

Adults with eczema who also reported experiencing fatigue (aOR, 1.59; 95% CI, 1.16-2.19), daytime sleepiness (aOR, 1.81), or insomnia (aOR, 1.74) had higher rates of FBJI than individuals with sleep symptoms but no eczema. Adults with both eczema and psychiatric or behavioral disorders also were more likely to experience FBJI than individuals suffering from eczema alone, or individuals suffering from psychiatric and behavioral disorders, but not eczema.

“Taken together, these data suggest that adult eczema is a previously unrecognized risk factor for fracture and other injury, emphasizing the importance of developing safer and more effective clinical interventions for itch and sleep problems in eczema, as well as preventive measures for injury risk reduction in eczema,” wrote Dr. Garg and Dr. Silverberg. The authors reported no relevant financial disclosures.

[email protected]

Eczema in adulthood is directly associated with an increase in incidence of injuries that cause physical limitations, particularly fracture, bone, and joint injuries, according to the results of a prospective study published online in JAMA Dermatology.

“The risk of bone fracture and other injury causing limitation in adults with eczema has been largely unexplored,” noted Dr. Nitin Garg and Dr. Jonathan I. Silverberg of Northwestern University in Chicago.

“Patients with eczema may be at risk of fracture given their use of systemic corticosteroids, which may decrease bone mineral density [and] therefore, studies describing the prevalence of fracture among adults with eczema are needed,” they added (JAMA Dermatol. 2015;151:33-41 [doi:10.1001/jamadermatol.2014.2098]).

©aniaostudio/Thinkstock.com

Dr. Garg and Dr. Silverberg used data from the 2012 National Health Interview Survey, which was conducted by the National Center for Health Statistics, to create their prospective, questionnaire-based study. The final analysis included 34,500 adults aged 18-85 years. They controlled for factors such as age, sex, race, Hispanic origin, household income, highest level of household education, family structure, and whether or not the subject was born in the United States.

The prevalence of self-reported eczema or skin allergy was 7.2%, the prevalence of any limitation-causing injury was 2.0%, and any limitation-causing injury in the past 12 months among adults was 7.2%. A fracture and bone or joint injury (FBJI) causing limitation was reported by 1.5% of the study population and other types of injury causing limitation were reported by 0.6%. The prevalence of FBJI causing limitation increased gradually with age, to peak in subjects aged 50-69 years, decreasing thereafter.

In a logistic regression analysis, adults with eczema had a 44% increased risk of any injury causing limitation (adjusted odds ratio, 1.44), and a 67% increased risk of FBJI (aOR, 1.67).

Adults with eczema who also reported experiencing fatigue (aOR, 1.59; 95% CI, 1.16-2.19), daytime sleepiness (aOR, 1.81), or insomnia (aOR, 1.74) had higher rates of FBJI than individuals with sleep symptoms but no eczema. Adults with both eczema and psychiatric or behavioral disorders also were more likely to experience FBJI than individuals suffering from eczema alone, or individuals suffering from psychiatric and behavioral disorders, but not eczema.

“Taken together, these data suggest that adult eczema is a previously unrecognized risk factor for fracture and other injury, emphasizing the importance of developing safer and more effective clinical interventions for itch and sleep problems in eczema, as well as preventive measures for injury risk reduction in eczema,” wrote Dr. Garg and Dr. Silverberg. The authors reported no relevant financial disclosures.

[email protected]

Eczema in adulthood is directly associated with an increase in incidence of injuries that cause physical limitations, particularly fracture, bone, and joint injuries, according to the results of a prospective study published online in JAMA Dermatology.

“The risk of bone fracture and other injury causing limitation in adults with eczema has been largely unexplored,” noted Dr. Nitin Garg and Dr. Jonathan I. Silverberg of Northwestern University in Chicago.

“Patients with eczema may be at risk of fracture given their use of systemic corticosteroids, which may decrease bone mineral density [and] therefore, studies describing the prevalence of fracture among adults with eczema are needed,” they added (JAMA Dermatol. 2015;151:33-41 [doi:10.1001/jamadermatol.2014.2098]).

©aniaostudio/Thinkstock.com

Dr. Garg and Dr. Silverberg used data from the 2012 National Health Interview Survey, which was conducted by the National Center for Health Statistics, to create their prospective, questionnaire-based study. The final analysis included 34,500 adults aged 18-85 years. They controlled for factors such as age, sex, race, Hispanic origin, household income, highest level of household education, family structure, and whether or not the subject was born in the United States.

The prevalence of self-reported eczema or skin allergy was 7.2%, the prevalence of any limitation-causing injury was 2.0%, and any limitation-causing injury in the past 12 months among adults was 7.2%. A fracture and bone or joint injury (FBJI) causing limitation was reported by 1.5% of the study population and other types of injury causing limitation were reported by 0.6%. The prevalence of FBJI causing limitation increased gradually with age, to peak in subjects aged 50-69 years, decreasing thereafter.

In a logistic regression analysis, adults with eczema had a 44% increased risk of any injury causing limitation (adjusted odds ratio, 1.44), and a 67% increased risk of FBJI (aOR, 1.67).

Adults with eczema who also reported experiencing fatigue (aOR, 1.59; 95% CI, 1.16-2.19), daytime sleepiness (aOR, 1.81), or insomnia (aOR, 1.74) had higher rates of FBJI than individuals with sleep symptoms but no eczema. Adults with both eczema and psychiatric or behavioral disorders also were more likely to experience FBJI than individuals suffering from eczema alone, or individuals suffering from psychiatric and behavioral disorders, but not eczema.

“Taken together, these data suggest that adult eczema is a previously unrecognized risk factor for fracture and other injury, emphasizing the importance of developing safer and more effective clinical interventions for itch and sleep problems in eczema, as well as preventive measures for injury risk reduction in eczema,” wrote Dr. Garg and Dr. Silverberg. The authors reported no relevant financial disclosures.

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Hot flashes are associated with a significant increase in the risk of hip fracture, regardless of age, body mass index, and other confounders such as smoking, according to analysis of data from the Women’s Health Study.

The prospective, observational study among 4,867 women aged 50-79 years found a 78% increase in the risk of hip fracture among women with moderate to severe menopausal vasomotor symptoms at baseline, compared with women with no symptoms.

Vasomotor symptom severity was also inversely associated with bone mineral density (BMD) at both the femoral neck and the spine. Compared with women who had no vasomotor symptoms, those with moderate or severe symptoms had 0.015 g/cm² lower femoral neck BMD and 0.016 g/cm² lower lumbar spine BMD, according to an analysis published on Dec. 18 in the Journal of Clinical Endocrinology and Metabolism (2014 [doi:10.1210/jc.2014-3062]).

“Despite being younger and heavier than asymptomatic women, characteristics associated with higher BMD, women with moderate/severe [vasomotor symptoms] had a higher risk of hip fractures that was also independent of other established risk factors for fractures,” wrote Dr. Carolyn J. Crandall of the University of California, Los Angeles, and her colleagues.

The study was funded by the National Institutes of Health. Two of the study authors reported consulting and other financial relationships with drug and device companies.

Hot flashes are associated with a significant increase in the risk of hip fracture, regardless of age, body mass index, and other confounders such as smoking, according to analysis of data from the Women’s Health Study.

The prospective, observational study among 4,867 women aged 50-79 years found a 78% increase in the risk of hip fracture among women with moderate to severe menopausal vasomotor symptoms at baseline, compared with women with no symptoms.

Vasomotor symptom severity was also inversely associated with bone mineral density (BMD) at both the femoral neck and the spine. Compared with women who had no vasomotor symptoms, those with moderate or severe symptoms had 0.015 g/cm² lower femoral neck BMD and 0.016 g/cm² lower lumbar spine BMD, according to an analysis published on Dec. 18 in the Journal of Clinical Endocrinology and Metabolism (2014 [doi:10.1210/jc.2014-3062]).

“Despite being younger and heavier than asymptomatic women, characteristics associated with higher BMD, women with moderate/severe [vasomotor symptoms] had a higher risk of hip fractures that was also independent of other established risk factors for fractures,” wrote Dr. Carolyn J. Crandall of the University of California, Los Angeles, and her colleagues.

The study was funded by the National Institutes of Health. Two of the study authors reported consulting and other financial relationships with drug and device companies.

Hot flashes are associated with a significant increase in the risk of hip fracture, regardless of age, body mass index, and other confounders such as smoking, according to analysis of data from the Women’s Health Study.

The prospective, observational study among 4,867 women aged 50-79 years found a 78% increase in the risk of hip fracture among women with moderate to severe menopausal vasomotor symptoms at baseline, compared with women with no symptoms.

Vasomotor symptom severity was also inversely associated with bone mineral density (BMD) at both the femoral neck and the spine. Compared with women who had no vasomotor symptoms, those with moderate or severe symptoms had 0.015 g/cm² lower femoral neck BMD and 0.016 g/cm² lower lumbar spine BMD, according to an analysis published on Dec. 18 in the Journal of Clinical Endocrinology and Metabolism (2014 [doi:10.1210/jc.2014-3062]).

“Despite being younger and heavier than asymptomatic women, characteristics associated with higher BMD, women with moderate/severe [vasomotor symptoms] had a higher risk of hip fractures that was also independent of other established risk factors for fractures,” wrote Dr. Carolyn J. Crandall of the University of California, Los Angeles, and her colleagues.

The study was funded by the National Institutes of Health. Two of the study authors reported consulting and other financial relationships with drug and device companies.