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What underlies post–bariatric surgery bone fragility?
BOSTON – Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.
said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.
It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.
With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.
After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).
A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.
HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.
A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.
All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.
Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).
Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.
Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.
Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.
However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).
Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.
How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.
All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.
Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.
BOSTON – Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.
said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.
It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.
With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.
After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).
A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.
HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.
A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.
All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.
Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).
Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.
Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.
Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.
However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).
Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.
How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.
All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.
Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.
BOSTON – Charting a healthy path for patients after bariatric surgery can be complicated and addressing bone health is an important part of the endocrinologist’s role in keeping patients safe from postsurgical fractures, according to John Bilezikian, MD.
said Dr. Bilezikian, speaking during a bariatric surgery–focused session at the annual scientific & clinical congress of the American Academy of Clinical Endocrinologists.
It’s not easy to assess bone health, even before surgery, said Dr. Bilezikian. Even objective measures of bone density, such as dual-energy x-ray absorptiometry (DXA), may be skewed: very high fat mass causes artifact that interferes with accurate measurement of bone density, and DXA can’t distinguish between cortical and trabecular bone. The latter is a particular issue in high body mass index patients, since obesity is known to be associated with a more fragile bone microarchitecture, said Dr. Bilezikian, the Dorothy L. and Daniel H. Silberberg Professor of Medicine and director of the metabolic bone diseases unit at Columbia University, New York.
With these caveats in mind, Dr. Bilezikian said, there are some lessons to be learned from existing research to better manage bone health in bariatric patients.
After Roux-en-Y gastric bypass surgery (RYGB), bone turnover soon increases, with bone resorption markers increasing by up to 200% in the first 12-18 months after surgery. Bone formation markers also are elevated but to a lesser extent, said Dr. Bilezikian. Over time, the weight loss from RYGB is associated with a significant drop in bone mineral density (BMD) at weight-bearing sites. Weight loss was associated with bone loss at the total hip (r = 0.70; P less than .0003) and femoral neck (r = 0.47; P = .03 (J Clin Endocrinol Metab. 2013 Feb;98[2] 541-9).
A newer-technology, high-resolution peripheral quantitative CT (HR-pQCT) offers a noninvasive look not just at bone size and density but also at microarchitecture, including cortical thickness and details of trabecular structure. This technology “can help elucidate the structural basis for fragility,” said Dr. Bilezikian.
HR-pQCT was used in a recent study (J Bone Min Res. 2017 Dec. 27. doi: 10.1002/jbmr.3371) that followed 48 patients for 1 year after RYGB. Using HR-pQCT, DXA, and serum markers of bone turnover, the researchers found significant decrease in BMD and estimated decrease in bone strength after RYGB. Bone cortex became increasingly porous as well. Taken together, these changes may indicate an increased fracture risk, concluded the investigators.
A longer study that followed RYGB recipients for 2 years and used similar imaging and serum parameters also found that participants had decreased BMD. Tellingly, these investigators saw more marked increase in cortical porosity in the second year after bypass. Estimated bone strength continued to decline during the study period, even after weight loss had stopped.
All of these findings, said Dr. Bilezikian, point to a pathogenetic process other than weight loss that promotes the deteriorating bone microarchitecture seen years after RYGB. “Loss of bone mass and skeletal deterioration after gastric bypass surgery cannot be explained by weight loss alone,” said Dr. Bilezikian.
Another recent study was able to follow a small cohort of patients for a full 5 years, using DXA, lumbar CT, and Hr-pQCT. Though weight loss stabilized after 2 years and 25-OH D and calcium levels were unchanged from presurgical baseline, bone density continued to drop, and bone microarchitecture further deteriorated, said Dr. Bilezikian (Greenblatt L et al. ASBMR 2017, Abstract 1125).
Initially, post–bariatric surgery weight loss may induce bone changes because of skeletal unloading; further down the road, estrogen production by adipose tissue is decreased with ongoing fat loss, and sarcopenia may have an adverse effect on bone microarchitecture. Postsurgical malabsorption may also be an early mechanism of bone loss.
Other hormonal changes can include secondary hyperparathyroidism. Leptin, adiponectin, and peptide YY levels also may be altered.
Do these changes in BMD and bone architecture result in increased fracture risk? This question is difficult to answer, for the same reasons that other bariatric surgery research can be challenging, said Dr. Bilezikian. There is heterogeneity of procedures and supplement regimens, sample sizes can be small, follow-up times short, and adherence often is not tracked.
However, there are some clues that RYGB may be associated with an increased risk of all fractures and of fragility fractures, with appendicular fractures seen most frequently (Osteoporos Int. 2014 Jan; 25[1]:151-8). A larger study that tracked 12,676 patients receiving bariatric surgery, 38,028 patients with obesity, and 126,760 nonobese participants found that the bariatric patients had a 4.1% risk of fracture at 4 years post surgery, compared with 2.7% and 2.4% fracture rates in the participants with and without obesity, respectively (BMJ. 2016;354:i3794).
Other retrospective studies have found “a time-dependent increase in nonvertebral fractures with Roux-en-Y gastric bypass compared to gastric banding,” said Dr. Bilezikian.
How can these risks be managed after gastric bypass surgery? “Strive for nutritional adequacy” as the first step, said Dr. Bilezikian, meaning that calcium and vitamin D should be prescribed – and adherence encouraged – as indicated. Levels of 25-OH D should be checked regularly, with supplementation managed to keep levels over 30 ng/mL, he said.
All patients should be encouraged to develop and maintain an appropriate exercise regimen, and BMD should be followed over time. Those caring for post–gastric bypass patients can still use a bisphosphonate or other bone-health medication, if indicated using standard parameters. However, “You probably shouldn’t use an oral bisphosphonate in this population,” said Dr. Bilezikian.
Dr. Bilezikian reported that he has consulting or advisory relationships with Amgen, Radius Pharmaceuticals, Shire Pharmaceuticals, and Ultragenyx, and serves on a data safety monitoring board for Regeneron.
REPORTING FROM AACE 2018
EULAR scientific program highlights spectrum of translational research
EULAR 2018’s scientific program in Amsterdam is packed with lectures, clinical and basic science symposia, workshops, and special interest sessions covering the full spectrum of rheumatic diseases, said Dr. Robert Landewé, chair of the Scientific Program Committee.
“More than 5,000 scientific abstracts were submitted, which is an absolute, all-time record,” Dr. Landewé said. Four experts scored each abstract, and only the top 7% were invited for oral presentation during abstract sessions or symposia, he explained in an interview.
Wednesday, June 13
A high point of the 2018 scientific program is Wednesday’s opening plenary session, which will feature abstracts that were handpicked by Dr. Landewé and Dr. Thomas Dörner, professor of rheumatology at Charite Universitätsmedizin, Berlin. “This session includes highly scored abstracts, including late-breakers, on current advances in therapeutics and disease classification,” said Dr. Dörner, who chaired this year’s Abstract Selection Committee.
The plenary abstract session will cover new findings on gout and cardiovascular disease from CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), long-term mortality in patients with early RA from the COBRA (Combinatietherapie Bij Reumatoide Artritis) study, the use of zoledronic acid to treat knee osteoarthritis with bone lesions, and the relationship between bisphosphonate drug holidays and hip fracture risk. Researchers also will discuss baricitinib in systemic lupus erythematosus (SLE), the value of MRI when treating remitted RA to target, the validation of SLE classification criteria, and draft classification criteria for ANCA-associated vasculitides.
A notable clinical science session on Wednesday will cover cancer and inflammation, Dr. Landewé said. “This is a topic of increasing interest because cancer and inflammation share mutual pathways.”
Novel cancer therapies such as immune checkpoint inhibitors have improved outcomes across a range of tumor types, but also can induce rheumatic disease, he added. Accordingly, presenters will discuss inflammation as “friend” versus “foe” in cancer treatment, the role of tumor necrosis factor in cancer, and risk of malignancy among patients with RA.
Also on Wednesday, a session will tackle the relationship between psychological distress and pain in immune-mediated disease. “Pain is the major symptom of rheumatic diseases, and the role of the psyche remains poorly understood,” Dr. Landewé said. “But we know one thing for sure: There is an association, and speakers from outside the field of rheumatology will help explain.”
Attendees at this bench-to-bedside session will learn how distress appears to exacerbate arthritis pain and how managing psychological stress can help optimize outcomes in arthritis pain. Experts also will describe research on integrated brain pathways in pain and distress, as well as risk factors for cognitive impairment in RA.
Thursday, June 14
Topics in this session will include the use of estrogens and other hormonal therapies in patients with rheumatic disease, registry studies of rheumatologic conditions during pregnancy, and how clinicians can best discuss sexual concerns with their rheumatology patients.
Another clinical science session scheduled for Thursday afternoon will delve into structural damage progression in patients with axial spondyloarthritis, Dr. Landewé said. “Can we inhibit this structural progression? Can we show it? Does it make sense? And which drug company will win the battle to have the precedent?”
He hopes that Dr. Désirée van der Heijde of the Netherlands and Dr. Xenofon Baraliakos of Germany will help answer these questions when they discuss the latest evidence on identifying and treating clinically relevant structural progression. Also in this session, researchers will describe the combined effects of tumor necrosis factor inhibitors and NSAIDs on radiographic progression in ankylosing spondylitis, and MRI evidence supporting treating early axial spondyloarthritis to target with the goal of achieving sustained remission of inflammation.
Also on Thursday afternoon, a case-based session will take a deep dive into giant cell arteritis (GCA), Dr. Landewé noted. Attendees will learn about diagnosing and managing vision loss and stroke and the latest on corticosteroid therapy in GCA. The session also will cover biologics. “Giant cell arteritis has entered the field of biologicals!” said Dr. Landewé. “This has major implications for this disease and the clinical choices to be made.”
The past 5 decades have seen marked progress in the diagnosis and treatment of SLE, with corresponding improvements in survival and quality of life. “Still, lupus is awfully difficult,” Dr. Landewé said. “Therefore, we have planned a classical bench-to-bedside symposium to provide an all-inclusive look at current thinking and future developments.”
Talks during this Thursday afternoon session will cover the latest findings on the pathogenesis of SLE, the clinical significance of autoantibodies, distinguishing early SLE from mimics, and the role of blood-brain barrier permeability and neuropsychiatric manifestations of SLE and progressive systemic sclerosis.
Friday, June 15
For the first time, the scientific program also will include a clinical science session held jointly with the European Society of Musculoskeletal Radiology (ESSR). Dr. Joachim Sieper of Germany and ESSR President Dr. Monique Reijnierse of the Netherlands will cochair the Friday afternoon session on the role of MRI in rheumatology. Attendees from both organizations will learn when to use MRI in early and established RA and spondyloarthritis, and how to interpret the results, with abundant time built in for questions and answers. Dr. Landewé called the joint session “a test case” for exciting web-based interactions between EULAR and ESSR.
Another clinical science session on Friday afternoon will dive into the diagnosis of spondyloarthritis, which Dr. Landewé called “a matter of recognizing patterns, not ticking boxes on a list of criteria. This symposium leads you through the art of pattern recognition.”
Later on Friday afternoon, a session will explore advances in biologic therapy of small-vessel vasculitis, he added. “Biologic disease-modifying antirheumatic drugs [bDMARDs] are becoming more and more important in this area of expanding interest.” Experts will address complement inhibition in ANCA-associated vasculitis (AAV), the use of induction and maintenance rituximab in AAV, the evolving role of mepolizumab in eosinophilic granulomatosis with polyangiitis, survival in AAV, and the use of rituximab for treating children with granulomatosis with polyangiitis and microscopic polyangiitis.
Saturday, June 16
On Saturday, a bench-to-bedside session will cover gout and kidney function. “This is an area with important new insights,” Dr. Dörner said. Presenters will discuss the genetics of hyperuricemia, renal urate transporters, and the pros and cons of using xanthine oxidase inhibitors to treat chronic kidney disease. Researchers will also cover studies of impaired neutrophil chemotaxis in patients with chronic kidney disease and hyperuricemia, and the relationship between renal medullar hyperechogenicity and gout severity.
Also on Saturday, a clinical science session titled, “Rheumatoid arthritis: Is it all in your head?” will explore emerging data on the relationship between inflammation and depression. Patients with RA often face both clinical depression and social isolation, and these complex psychosocial conditions can worsen one another. “In addition to proper drug choice, treating RA effectively depends on how concomitant problems, such as nonspecific pain, depression, and social isolation, are coped with in a broad context,” Dr. Landewé said. “When it comes to optimal management, rheumatologists need to communicate and prescribe, not just prescribe.”
Christian Apfelbacher, PhD, of Germany will discuss prevention and treatment strategies and Dr. Jonathan Cavanagh of the United Kingdom will cover neuroimaging in RA. Researchers also will discuss new findings on pain, depression, and anxiety in patients recently diagnosed with RA.
Also on Saturday, a special session will cover EULAR’s initiatives to improve clinical approaches (ESSCA), Dr. Dörner noted. This effort has produced new or updated recommendations on topics such as vaccination, Sjögren’s syndrome, glucocorticoid therapy, and management of hand osteoarthritis, he said. “These recommendations follow a number of others and are expected to impact clinical science as well as clinical practice.”
EULAR 2018’s scientific program in Amsterdam is packed with lectures, clinical and basic science symposia, workshops, and special interest sessions covering the full spectrum of rheumatic diseases, said Dr. Robert Landewé, chair of the Scientific Program Committee.
“More than 5,000 scientific abstracts were submitted, which is an absolute, all-time record,” Dr. Landewé said. Four experts scored each abstract, and only the top 7% were invited for oral presentation during abstract sessions or symposia, he explained in an interview.
Wednesday, June 13
A high point of the 2018 scientific program is Wednesday’s opening plenary session, which will feature abstracts that were handpicked by Dr. Landewé and Dr. Thomas Dörner, professor of rheumatology at Charite Universitätsmedizin, Berlin. “This session includes highly scored abstracts, including late-breakers, on current advances in therapeutics and disease classification,” said Dr. Dörner, who chaired this year’s Abstract Selection Committee.
The plenary abstract session will cover new findings on gout and cardiovascular disease from CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), long-term mortality in patients with early RA from the COBRA (Combinatietherapie Bij Reumatoide Artritis) study, the use of zoledronic acid to treat knee osteoarthritis with bone lesions, and the relationship between bisphosphonate drug holidays and hip fracture risk. Researchers also will discuss baricitinib in systemic lupus erythematosus (SLE), the value of MRI when treating remitted RA to target, the validation of SLE classification criteria, and draft classification criteria for ANCA-associated vasculitides.
A notable clinical science session on Wednesday will cover cancer and inflammation, Dr. Landewé said. “This is a topic of increasing interest because cancer and inflammation share mutual pathways.”
Novel cancer therapies such as immune checkpoint inhibitors have improved outcomes across a range of tumor types, but also can induce rheumatic disease, he added. Accordingly, presenters will discuss inflammation as “friend” versus “foe” in cancer treatment, the role of tumor necrosis factor in cancer, and risk of malignancy among patients with RA.
Also on Wednesday, a session will tackle the relationship between psychological distress and pain in immune-mediated disease. “Pain is the major symptom of rheumatic diseases, and the role of the psyche remains poorly understood,” Dr. Landewé said. “But we know one thing for sure: There is an association, and speakers from outside the field of rheumatology will help explain.”
Attendees at this bench-to-bedside session will learn how distress appears to exacerbate arthritis pain and how managing psychological stress can help optimize outcomes in arthritis pain. Experts also will describe research on integrated brain pathways in pain and distress, as well as risk factors for cognitive impairment in RA.
Thursday, June 14
Topics in this session will include the use of estrogens and other hormonal therapies in patients with rheumatic disease, registry studies of rheumatologic conditions during pregnancy, and how clinicians can best discuss sexual concerns with their rheumatology patients.
Another clinical science session scheduled for Thursday afternoon will delve into structural damage progression in patients with axial spondyloarthritis, Dr. Landewé said. “Can we inhibit this structural progression? Can we show it? Does it make sense? And which drug company will win the battle to have the precedent?”
He hopes that Dr. Désirée van der Heijde of the Netherlands and Dr. Xenofon Baraliakos of Germany will help answer these questions when they discuss the latest evidence on identifying and treating clinically relevant structural progression. Also in this session, researchers will describe the combined effects of tumor necrosis factor inhibitors and NSAIDs on radiographic progression in ankylosing spondylitis, and MRI evidence supporting treating early axial spondyloarthritis to target with the goal of achieving sustained remission of inflammation.
Also on Thursday afternoon, a case-based session will take a deep dive into giant cell arteritis (GCA), Dr. Landewé noted. Attendees will learn about diagnosing and managing vision loss and stroke and the latest on corticosteroid therapy in GCA. The session also will cover biologics. “Giant cell arteritis has entered the field of biologicals!” said Dr. Landewé. “This has major implications for this disease and the clinical choices to be made.”
The past 5 decades have seen marked progress in the diagnosis and treatment of SLE, with corresponding improvements in survival and quality of life. “Still, lupus is awfully difficult,” Dr. Landewé said. “Therefore, we have planned a classical bench-to-bedside symposium to provide an all-inclusive look at current thinking and future developments.”
Talks during this Thursday afternoon session will cover the latest findings on the pathogenesis of SLE, the clinical significance of autoantibodies, distinguishing early SLE from mimics, and the role of blood-brain barrier permeability and neuropsychiatric manifestations of SLE and progressive systemic sclerosis.
Friday, June 15
For the first time, the scientific program also will include a clinical science session held jointly with the European Society of Musculoskeletal Radiology (ESSR). Dr. Joachim Sieper of Germany and ESSR President Dr. Monique Reijnierse of the Netherlands will cochair the Friday afternoon session on the role of MRI in rheumatology. Attendees from both organizations will learn when to use MRI in early and established RA and spondyloarthritis, and how to interpret the results, with abundant time built in for questions and answers. Dr. Landewé called the joint session “a test case” for exciting web-based interactions between EULAR and ESSR.
Another clinical science session on Friday afternoon will dive into the diagnosis of spondyloarthritis, which Dr. Landewé called “a matter of recognizing patterns, not ticking boxes on a list of criteria. This symposium leads you through the art of pattern recognition.”
Later on Friday afternoon, a session will explore advances in biologic therapy of small-vessel vasculitis, he added. “Biologic disease-modifying antirheumatic drugs [bDMARDs] are becoming more and more important in this area of expanding interest.” Experts will address complement inhibition in ANCA-associated vasculitis (AAV), the use of induction and maintenance rituximab in AAV, the evolving role of mepolizumab in eosinophilic granulomatosis with polyangiitis, survival in AAV, and the use of rituximab for treating children with granulomatosis with polyangiitis and microscopic polyangiitis.
Saturday, June 16
On Saturday, a bench-to-bedside session will cover gout and kidney function. “This is an area with important new insights,” Dr. Dörner said. Presenters will discuss the genetics of hyperuricemia, renal urate transporters, and the pros and cons of using xanthine oxidase inhibitors to treat chronic kidney disease. Researchers will also cover studies of impaired neutrophil chemotaxis in patients with chronic kidney disease and hyperuricemia, and the relationship between renal medullar hyperechogenicity and gout severity.
Also on Saturday, a clinical science session titled, “Rheumatoid arthritis: Is it all in your head?” will explore emerging data on the relationship between inflammation and depression. Patients with RA often face both clinical depression and social isolation, and these complex psychosocial conditions can worsen one another. “In addition to proper drug choice, treating RA effectively depends on how concomitant problems, such as nonspecific pain, depression, and social isolation, are coped with in a broad context,” Dr. Landewé said. “When it comes to optimal management, rheumatologists need to communicate and prescribe, not just prescribe.”
Christian Apfelbacher, PhD, of Germany will discuss prevention and treatment strategies and Dr. Jonathan Cavanagh of the United Kingdom will cover neuroimaging in RA. Researchers also will discuss new findings on pain, depression, and anxiety in patients recently diagnosed with RA.
Also on Saturday, a special session will cover EULAR’s initiatives to improve clinical approaches (ESSCA), Dr. Dörner noted. This effort has produced new or updated recommendations on topics such as vaccination, Sjögren’s syndrome, glucocorticoid therapy, and management of hand osteoarthritis, he said. “These recommendations follow a number of others and are expected to impact clinical science as well as clinical practice.”
EULAR 2018’s scientific program in Amsterdam is packed with lectures, clinical and basic science symposia, workshops, and special interest sessions covering the full spectrum of rheumatic diseases, said Dr. Robert Landewé, chair of the Scientific Program Committee.
“More than 5,000 scientific abstracts were submitted, which is an absolute, all-time record,” Dr. Landewé said. Four experts scored each abstract, and only the top 7% were invited for oral presentation during abstract sessions or symposia, he explained in an interview.
Wednesday, June 13
A high point of the 2018 scientific program is Wednesday’s opening plenary session, which will feature abstracts that were handpicked by Dr. Landewé and Dr. Thomas Dörner, professor of rheumatology at Charite Universitätsmedizin, Berlin. “This session includes highly scored abstracts, including late-breakers, on current advances in therapeutics and disease classification,” said Dr. Dörner, who chaired this year’s Abstract Selection Committee.
The plenary abstract session will cover new findings on gout and cardiovascular disease from CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), long-term mortality in patients with early RA from the COBRA (Combinatietherapie Bij Reumatoide Artritis) study, the use of zoledronic acid to treat knee osteoarthritis with bone lesions, and the relationship between bisphosphonate drug holidays and hip fracture risk. Researchers also will discuss baricitinib in systemic lupus erythematosus (SLE), the value of MRI when treating remitted RA to target, the validation of SLE classification criteria, and draft classification criteria for ANCA-associated vasculitides.
A notable clinical science session on Wednesday will cover cancer and inflammation, Dr. Landewé said. “This is a topic of increasing interest because cancer and inflammation share mutual pathways.”
Novel cancer therapies such as immune checkpoint inhibitors have improved outcomes across a range of tumor types, but also can induce rheumatic disease, he added. Accordingly, presenters will discuss inflammation as “friend” versus “foe” in cancer treatment, the role of tumor necrosis factor in cancer, and risk of malignancy among patients with RA.
Also on Wednesday, a session will tackle the relationship between psychological distress and pain in immune-mediated disease. “Pain is the major symptom of rheumatic diseases, and the role of the psyche remains poorly understood,” Dr. Landewé said. “But we know one thing for sure: There is an association, and speakers from outside the field of rheumatology will help explain.”
Attendees at this bench-to-bedside session will learn how distress appears to exacerbate arthritis pain and how managing psychological stress can help optimize outcomes in arthritis pain. Experts also will describe research on integrated brain pathways in pain and distress, as well as risk factors for cognitive impairment in RA.
Thursday, June 14
Topics in this session will include the use of estrogens and other hormonal therapies in patients with rheumatic disease, registry studies of rheumatologic conditions during pregnancy, and how clinicians can best discuss sexual concerns with their rheumatology patients.
Another clinical science session scheduled for Thursday afternoon will delve into structural damage progression in patients with axial spondyloarthritis, Dr. Landewé said. “Can we inhibit this structural progression? Can we show it? Does it make sense? And which drug company will win the battle to have the precedent?”
He hopes that Dr. Désirée van der Heijde of the Netherlands and Dr. Xenofon Baraliakos of Germany will help answer these questions when they discuss the latest evidence on identifying and treating clinically relevant structural progression. Also in this session, researchers will describe the combined effects of tumor necrosis factor inhibitors and NSAIDs on radiographic progression in ankylosing spondylitis, and MRI evidence supporting treating early axial spondyloarthritis to target with the goal of achieving sustained remission of inflammation.
Also on Thursday afternoon, a case-based session will take a deep dive into giant cell arteritis (GCA), Dr. Landewé noted. Attendees will learn about diagnosing and managing vision loss and stroke and the latest on corticosteroid therapy in GCA. The session also will cover biologics. “Giant cell arteritis has entered the field of biologicals!” said Dr. Landewé. “This has major implications for this disease and the clinical choices to be made.”
The past 5 decades have seen marked progress in the diagnosis and treatment of SLE, with corresponding improvements in survival and quality of life. “Still, lupus is awfully difficult,” Dr. Landewé said. “Therefore, we have planned a classical bench-to-bedside symposium to provide an all-inclusive look at current thinking and future developments.”
Talks during this Thursday afternoon session will cover the latest findings on the pathogenesis of SLE, the clinical significance of autoantibodies, distinguishing early SLE from mimics, and the role of blood-brain barrier permeability and neuropsychiatric manifestations of SLE and progressive systemic sclerosis.
Friday, June 15
For the first time, the scientific program also will include a clinical science session held jointly with the European Society of Musculoskeletal Radiology (ESSR). Dr. Joachim Sieper of Germany and ESSR President Dr. Monique Reijnierse of the Netherlands will cochair the Friday afternoon session on the role of MRI in rheumatology. Attendees from both organizations will learn when to use MRI in early and established RA and spondyloarthritis, and how to interpret the results, with abundant time built in for questions and answers. Dr. Landewé called the joint session “a test case” for exciting web-based interactions between EULAR and ESSR.
Another clinical science session on Friday afternoon will dive into the diagnosis of spondyloarthritis, which Dr. Landewé called “a matter of recognizing patterns, not ticking boxes on a list of criteria. This symposium leads you through the art of pattern recognition.”
Later on Friday afternoon, a session will explore advances in biologic therapy of small-vessel vasculitis, he added. “Biologic disease-modifying antirheumatic drugs [bDMARDs] are becoming more and more important in this area of expanding interest.” Experts will address complement inhibition in ANCA-associated vasculitis (AAV), the use of induction and maintenance rituximab in AAV, the evolving role of mepolizumab in eosinophilic granulomatosis with polyangiitis, survival in AAV, and the use of rituximab for treating children with granulomatosis with polyangiitis and microscopic polyangiitis.
Saturday, June 16
On Saturday, a bench-to-bedside session will cover gout and kidney function. “This is an area with important new insights,” Dr. Dörner said. Presenters will discuss the genetics of hyperuricemia, renal urate transporters, and the pros and cons of using xanthine oxidase inhibitors to treat chronic kidney disease. Researchers will also cover studies of impaired neutrophil chemotaxis in patients with chronic kidney disease and hyperuricemia, and the relationship between renal medullar hyperechogenicity and gout severity.
Also on Saturday, a clinical science session titled, “Rheumatoid arthritis: Is it all in your head?” will explore emerging data on the relationship between inflammation and depression. Patients with RA often face both clinical depression and social isolation, and these complex psychosocial conditions can worsen one another. “In addition to proper drug choice, treating RA effectively depends on how concomitant problems, such as nonspecific pain, depression, and social isolation, are coped with in a broad context,” Dr. Landewé said. “When it comes to optimal management, rheumatologists need to communicate and prescribe, not just prescribe.”
Christian Apfelbacher, PhD, of Germany will discuss prevention and treatment strategies and Dr. Jonathan Cavanagh of the United Kingdom will cover neuroimaging in RA. Researchers also will discuss new findings on pain, depression, and anxiety in patients recently diagnosed with RA.
Also on Saturday, a special session will cover EULAR’s initiatives to improve clinical approaches (ESSCA), Dr. Dörner noted. This effort has produced new or updated recommendations on topics such as vaccination, Sjögren’s syndrome, glucocorticoid therapy, and management of hand osteoarthritis, he said. “These recommendations follow a number of others and are expected to impact clinical science as well as clinical practice.”
FDA approves Prolia for glucocorticoid-induced osteoporosis
at high risk of fracture, the drug’s manufacturer Amgen announced May 21.
FDA approval was based on 12-month primary analysis results from a randomized, double-blind, phase 3 trial. Patients who received a 60-mg dose of Prolia subcutaneously every 6 months had greater lumbar spine bone mineral density at 1 year than did those who received a 5-mg dose of risedronate daily in all study subpopulations. These results were maintained after researchers controlled for gender, race, geographic region, and menopausal status, as well as baseline age, lumbar spine bone mineral density T score, and glucocorticoid dose within each subpopulation.
The most common adverse events associated with Prolia during the phase 3 study were back pain, hypertension, bronchitis, and headache, which are in line with previously reported safety data.
“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment. With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density,” lead study author Kenneth F. Saag, MD, professor of medicine at the University of Alabama, Birmingham, said in Amgen’s news release.
at high risk of fracture, the drug’s manufacturer Amgen announced May 21.
FDA approval was based on 12-month primary analysis results from a randomized, double-blind, phase 3 trial. Patients who received a 60-mg dose of Prolia subcutaneously every 6 months had greater lumbar spine bone mineral density at 1 year than did those who received a 5-mg dose of risedronate daily in all study subpopulations. These results were maintained after researchers controlled for gender, race, geographic region, and menopausal status, as well as baseline age, lumbar spine bone mineral density T score, and glucocorticoid dose within each subpopulation.
The most common adverse events associated with Prolia during the phase 3 study were back pain, hypertension, bronchitis, and headache, which are in line with previously reported safety data.
“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment. With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density,” lead study author Kenneth F. Saag, MD, professor of medicine at the University of Alabama, Birmingham, said in Amgen’s news release.
at high risk of fracture, the drug’s manufacturer Amgen announced May 21.
FDA approval was based on 12-month primary analysis results from a randomized, double-blind, phase 3 trial. Patients who received a 60-mg dose of Prolia subcutaneously every 6 months had greater lumbar spine bone mineral density at 1 year than did those who received a 5-mg dose of risedronate daily in all study subpopulations. These results were maintained after researchers controlled for gender, race, geographic region, and menopausal status, as well as baseline age, lumbar spine bone mineral density T score, and glucocorticoid dose within each subpopulation.
The most common adverse events associated with Prolia during the phase 3 study were back pain, hypertension, bronchitis, and headache, which are in line with previously reported safety data.
“Patients on long-term systemic glucocorticoid medications can experience a rapid reduction in bone mineral density within a few months of beginning treatment. With this approval, patients who receive treatment with glucocorticoids now have a new option to help improve their bone mineral density,” lead study author Kenneth F. Saag, MD, professor of medicine at the University of Alabama, Birmingham, said in Amgen’s news release.
VIDEO: BMI helps predict bone fragility in obese patients
BOSTON – An index that takes into account the ratio between body mass index (BMI) and bone mineral density (BMD) correlated well with trabecular bone scores, a newer assessment of bone fragility. The index may help predict risk for fragility fractures in individuals with obesity when trabecular bone scores are not available.
“Obesity is traditionally thought to be protective against bone fractures,” said Mikiko Watanabe, MD, an endocrinologist at Sapienza University of Rome. “But recent evidence suggests that this is not entirely true, especially in morbidly obese patients.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Lumbar spine BMD alone may not accurately capture bone fragility in patients with obesity, said Dr. Watanabe in an interview at the annual meeting of the American Association of Clinical Endocrinologists.
Adding the trabecular bone score (TBS) to BMD gives additional information about bone microarchitecture, refining risk assessment for fragility fractures. This newer technology, however, may not be readily available and may be associated with extra cost.
Accordingly, said Dr. Watanabe, the study’s senior investigator, Sapienza University’s Carla Lubrano, MD, had the idea to index bone density to BMI, and then see how well the ratio correlated to TBS; obesity is known to be associated with lower TBS scores, indicating increased bone fragility.
Living in Italy, with relatively fewer medical resources available, “We were trying to find some readily available index that could predict the risk of fracture as well as the indexes that are around right now,” said Dr. Watanabe.
“We did find some very interesting data in our population of over 2,000 obese patients living in Rome,” she said. “We do confirm something from the literature, where BMD tends to go high with increasing BMI.” Further, the relatively weak correlation between TBS and BMI was confirmed in the investigators’ work (r = 0.3).
“If you correct the BMD by BMI – so if you use our index – then the correlation becomes more stringent, and definitely so much better,” she said (r = 0.54).
Dr. Watanabe and her colleagues also conducted an analysis to see if there were differences between participants with and without metabolic syndrome. The 45.7% of participants who had metabolic syndrome had similar lumbar spine BMD scores to the rest of the cohort (1.067 versus 1.063 g/cm2, P = .50754).
However, both the TBS and BMD/BMI ratio were significantly lower for those with metabolic syndrome than for the metabolically healthy participants. The TBS, as expected, was 1.21 in patients with metabolic syndrome, and 1.31 in patients without metabolic syndrome; the BMD/BMI ratio followed the same pattern, with ratios of 0.28 for those with, and 0.30 for those without, metabolic syndrome (P less than .00001 for both).
Dr. Watanabe said that she and her associates are continuing research “to see whether our ratio is actually able to predict the risk of fractures." The hope, she said, is to use the BMD/BMI index together with or instead of TBS to better assess bone strength in patients with obesity.
Dr. Watanabe reported that she had no relevant conflicts of interest.
BOSTON – An index that takes into account the ratio between body mass index (BMI) and bone mineral density (BMD) correlated well with trabecular bone scores, a newer assessment of bone fragility. The index may help predict risk for fragility fractures in individuals with obesity when trabecular bone scores are not available.
“Obesity is traditionally thought to be protective against bone fractures,” said Mikiko Watanabe, MD, an endocrinologist at Sapienza University of Rome. “But recent evidence suggests that this is not entirely true, especially in morbidly obese patients.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Lumbar spine BMD alone may not accurately capture bone fragility in patients with obesity, said Dr. Watanabe in an interview at the annual meeting of the American Association of Clinical Endocrinologists.
Adding the trabecular bone score (TBS) to BMD gives additional information about bone microarchitecture, refining risk assessment for fragility fractures. This newer technology, however, may not be readily available and may be associated with extra cost.
Accordingly, said Dr. Watanabe, the study’s senior investigator, Sapienza University’s Carla Lubrano, MD, had the idea to index bone density to BMI, and then see how well the ratio correlated to TBS; obesity is known to be associated with lower TBS scores, indicating increased bone fragility.
Living in Italy, with relatively fewer medical resources available, “We were trying to find some readily available index that could predict the risk of fracture as well as the indexes that are around right now,” said Dr. Watanabe.
“We did find some very interesting data in our population of over 2,000 obese patients living in Rome,” she said. “We do confirm something from the literature, where BMD tends to go high with increasing BMI.” Further, the relatively weak correlation between TBS and BMI was confirmed in the investigators’ work (r = 0.3).
“If you correct the BMD by BMI – so if you use our index – then the correlation becomes more stringent, and definitely so much better,” she said (r = 0.54).
Dr. Watanabe and her colleagues also conducted an analysis to see if there were differences between participants with and without metabolic syndrome. The 45.7% of participants who had metabolic syndrome had similar lumbar spine BMD scores to the rest of the cohort (1.067 versus 1.063 g/cm2, P = .50754).
However, both the TBS and BMD/BMI ratio were significantly lower for those with metabolic syndrome than for the metabolically healthy participants. The TBS, as expected, was 1.21 in patients with metabolic syndrome, and 1.31 in patients without metabolic syndrome; the BMD/BMI ratio followed the same pattern, with ratios of 0.28 for those with, and 0.30 for those without, metabolic syndrome (P less than .00001 for both).
Dr. Watanabe said that she and her associates are continuing research “to see whether our ratio is actually able to predict the risk of fractures." The hope, she said, is to use the BMD/BMI index together with or instead of TBS to better assess bone strength in patients with obesity.
Dr. Watanabe reported that she had no relevant conflicts of interest.
BOSTON – An index that takes into account the ratio between body mass index (BMI) and bone mineral density (BMD) correlated well with trabecular bone scores, a newer assessment of bone fragility. The index may help predict risk for fragility fractures in individuals with obesity when trabecular bone scores are not available.
“Obesity is traditionally thought to be protective against bone fractures,” said Mikiko Watanabe, MD, an endocrinologist at Sapienza University of Rome. “But recent evidence suggests that this is not entirely true, especially in morbidly obese patients.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Lumbar spine BMD alone may not accurately capture bone fragility in patients with obesity, said Dr. Watanabe in an interview at the annual meeting of the American Association of Clinical Endocrinologists.
Adding the trabecular bone score (TBS) to BMD gives additional information about bone microarchitecture, refining risk assessment for fragility fractures. This newer technology, however, may not be readily available and may be associated with extra cost.
Accordingly, said Dr. Watanabe, the study’s senior investigator, Sapienza University’s Carla Lubrano, MD, had the idea to index bone density to BMI, and then see how well the ratio correlated to TBS; obesity is known to be associated with lower TBS scores, indicating increased bone fragility.
Living in Italy, with relatively fewer medical resources available, “We were trying to find some readily available index that could predict the risk of fracture as well as the indexes that are around right now,” said Dr. Watanabe.
“We did find some very interesting data in our population of over 2,000 obese patients living in Rome,” she said. “We do confirm something from the literature, where BMD tends to go high with increasing BMI.” Further, the relatively weak correlation between TBS and BMI was confirmed in the investigators’ work (r = 0.3).
“If you correct the BMD by BMI – so if you use our index – then the correlation becomes more stringent, and definitely so much better,” she said (r = 0.54).
Dr. Watanabe and her colleagues also conducted an analysis to see if there were differences between participants with and without metabolic syndrome. The 45.7% of participants who had metabolic syndrome had similar lumbar spine BMD scores to the rest of the cohort (1.067 versus 1.063 g/cm2, P = .50754).
However, both the TBS and BMD/BMI ratio were significantly lower for those with metabolic syndrome than for the metabolically healthy participants. The TBS, as expected, was 1.21 in patients with metabolic syndrome, and 1.31 in patients without metabolic syndrome; the BMD/BMI ratio followed the same pattern, with ratios of 0.28 for those with, and 0.30 for those without, metabolic syndrome (P less than .00001 for both).
Dr. Watanabe said that she and her associates are continuing research “to see whether our ratio is actually able to predict the risk of fractures." The hope, she said, is to use the BMD/BMI index together with or instead of TBS to better assess bone strength in patients with obesity.
Dr. Watanabe reported that she had no relevant conflicts of interest.
REPORTING FROM AACE 2018
AACE 2018: A dream team of presenters
Boston is the location and inspiration for the featured presentations at the annual meeting of the American Association of Clinical Endocrinologists, program chair Vin Tangpricha, MD, PhD, said in an interview.
The program agenda for the congress, held May 16-20, boasts 143 speakers, 66 distinct clinical endocrinology educational sessions, and an opening plenary presentation featuring one of modern medicine’s most renowned diabetes and obesity researchers, according to a statement from the AACE.
New Dimensions in Insulin Action and Why They Are Important to Know
C. Ronald Kahn, MD, chief academic officer and head of Integrative Physiology and Metabolism at Joslin Diabetes Center in Boston, pioneered revolutionary work with insulin receptors and insulin resistance in diabetes and obesity. What makes his presentation on Thursday from 8:30 a.m. to 9:15 a.m. a must-see is its focus on the future: “Many new drugs are being developed based on the research on how insulin works. This lecture will be exciting to hear what is in the pipeline for drugs that manipulate insulin action,” Dr. Tangpricha said.
Cushing’s Syndrome
Beta-Cell Regeneration
The work of Andrew F. Stewart, MD, scientific director of the Mount Sinai Diabetes, Obesity and Metabolism Institute in New York, leads research into the basic mechanisms, prevention, and treatment of metabolic diseases. “In the past, we thought that there was a fixed number of beta cells in the body. However, recent research by Dr. Stewart’s group suggests that beta cells can be stimulated to grow. This is very exciting and can shape the future of how we take care of diabetes,” noted Dr. Tangpricha. The session is on Friday from 8:20 a.m. to 9:05 a.m.
New Insights Into Thyroid Hormone Action
On Thursday from 11:15 a.m. to 12:00 p.m., Anthony N. Hollenberg, MD, will present “an outstanding review on thyroid hormone and action and how this impacts patient care of those with thyroid disease,” Dr. Tangpricha said. Dr. Hollenberg is chief of the thyroid unit and the division of endocrinology, diabetes, and metabolism at Beth Israel Deaconess Medical Center in Boston.
Current and Evolving Approaches for Osteoporosis Treatment
Sundeep Khosla, MD, an expert on bone loss, will distill the myriad osteoporosis treatments into useful information that can inform your practice now. “There have been a number of drugs that have been released for the treatment of osteoporosis. We are now in an era where we can consider using drugs targeted for specific populations or specific combinations,” Dr. Tangpricha commented. This session is on Saturday at 8:15 a.m. to 9:00 a.m.
Boston is the location and inspiration for the featured presentations at the annual meeting of the American Association of Clinical Endocrinologists, program chair Vin Tangpricha, MD, PhD, said in an interview.
The program agenda for the congress, held May 16-20, boasts 143 speakers, 66 distinct clinical endocrinology educational sessions, and an opening plenary presentation featuring one of modern medicine’s most renowned diabetes and obesity researchers, according to a statement from the AACE.
New Dimensions in Insulin Action and Why They Are Important to Know
C. Ronald Kahn, MD, chief academic officer and head of Integrative Physiology and Metabolism at Joslin Diabetes Center in Boston, pioneered revolutionary work with insulin receptors and insulin resistance in diabetes and obesity. What makes his presentation on Thursday from 8:30 a.m. to 9:15 a.m. a must-see is its focus on the future: “Many new drugs are being developed based on the research on how insulin works. This lecture will be exciting to hear what is in the pipeline for drugs that manipulate insulin action,” Dr. Tangpricha said.
Cushing’s Syndrome
Beta-Cell Regeneration
The work of Andrew F. Stewart, MD, scientific director of the Mount Sinai Diabetes, Obesity and Metabolism Institute in New York, leads research into the basic mechanisms, prevention, and treatment of metabolic diseases. “In the past, we thought that there was a fixed number of beta cells in the body. However, recent research by Dr. Stewart’s group suggests that beta cells can be stimulated to grow. This is very exciting and can shape the future of how we take care of diabetes,” noted Dr. Tangpricha. The session is on Friday from 8:20 a.m. to 9:05 a.m.
New Insights Into Thyroid Hormone Action
On Thursday from 11:15 a.m. to 12:00 p.m., Anthony N. Hollenberg, MD, will present “an outstanding review on thyroid hormone and action and how this impacts patient care of those with thyroid disease,” Dr. Tangpricha said. Dr. Hollenberg is chief of the thyroid unit and the division of endocrinology, diabetes, and metabolism at Beth Israel Deaconess Medical Center in Boston.
Current and Evolving Approaches for Osteoporosis Treatment
Sundeep Khosla, MD, an expert on bone loss, will distill the myriad osteoporosis treatments into useful information that can inform your practice now. “There have been a number of drugs that have been released for the treatment of osteoporosis. We are now in an era where we can consider using drugs targeted for specific populations or specific combinations,” Dr. Tangpricha commented. This session is on Saturday at 8:15 a.m. to 9:00 a.m.
Boston is the location and inspiration for the featured presentations at the annual meeting of the American Association of Clinical Endocrinologists, program chair Vin Tangpricha, MD, PhD, said in an interview.
The program agenda for the congress, held May 16-20, boasts 143 speakers, 66 distinct clinical endocrinology educational sessions, and an opening plenary presentation featuring one of modern medicine’s most renowned diabetes and obesity researchers, according to a statement from the AACE.
New Dimensions in Insulin Action and Why They Are Important to Know
C. Ronald Kahn, MD, chief academic officer and head of Integrative Physiology and Metabolism at Joslin Diabetes Center in Boston, pioneered revolutionary work with insulin receptors and insulin resistance in diabetes and obesity. What makes his presentation on Thursday from 8:30 a.m. to 9:15 a.m. a must-see is its focus on the future: “Many new drugs are being developed based on the research on how insulin works. This lecture will be exciting to hear what is in the pipeline for drugs that manipulate insulin action,” Dr. Tangpricha said.
Cushing’s Syndrome
Beta-Cell Regeneration
The work of Andrew F. Stewart, MD, scientific director of the Mount Sinai Diabetes, Obesity and Metabolism Institute in New York, leads research into the basic mechanisms, prevention, and treatment of metabolic diseases. “In the past, we thought that there was a fixed number of beta cells in the body. However, recent research by Dr. Stewart’s group suggests that beta cells can be stimulated to grow. This is very exciting and can shape the future of how we take care of diabetes,” noted Dr. Tangpricha. The session is on Friday from 8:20 a.m. to 9:05 a.m.
New Insights Into Thyroid Hormone Action
On Thursday from 11:15 a.m. to 12:00 p.m., Anthony N. Hollenberg, MD, will present “an outstanding review on thyroid hormone and action and how this impacts patient care of those with thyroid disease,” Dr. Tangpricha said. Dr. Hollenberg is chief of the thyroid unit and the division of endocrinology, diabetes, and metabolism at Beth Israel Deaconess Medical Center in Boston.
Current and Evolving Approaches for Osteoporosis Treatment
Sundeep Khosla, MD, an expert on bone loss, will distill the myriad osteoporosis treatments into useful information that can inform your practice now. “There have been a number of drugs that have been released for the treatment of osteoporosis. We are now in an era where we can consider using drugs targeted for specific populations or specific combinations,” Dr. Tangpricha commented. This session is on Saturday at 8:15 a.m. to 9:00 a.m.
FROM AACE 2018
Original research expands at AACE 2018
This year’s meeting, in Boston May 16-20, has brought in a record number of accepted abstracts – 1,126 – in all areas of endocrinology. The lion’s share focuses on diabetes, thyroid disease, and bone disease. Most will be presented in Poster Viewing and Judging sessions at 10:00 a.m on Thursday for young investigators and during a poster viewing and wine and cheese reception from 4:30 p.m. to 6:30 p.m. on Friday for senior investigators.
Of note, the mother lode of clinical trials, retrospective analyses, and registry studies will be shown at the senior investigator competition on Friday evening.
That viewing session will include two post hoc analyses of data from the global SUSTAIN trial program in the investigational GLP-1 receptor agonist semaglutide. The first, Abstract 245, examines whether reductions in body weight and HbA1c differed between elderly and younger patients in SUSTAIN 7. The second, Abstract 298, is an analysis of SUSTAIN 1-5 and 7, looking at semaglutide’s effectiveness across racial and ethnic subgroups.
Another large trial, CANVAS, will be represented in two abstracts in this Friday session. In CANVAS, canagliflozin for primary prevention didn’t significantly reduce cardiovascular events in patients with at-risk type 2 diabetes, but it did so convincingly in a secondary prevention population. Outcomes by age group will be presented in Abstract 233, while those by changes in HbA1c and use of antihyperglycemic drugs will be presented in Abstract 262.
Other studies of interest in this viewing session include but are not limited to a comparison of the effects of hypnosis and certified diabetes educators on weight loss and changes in HbA1c levels (Abstract 602) and an investigation into whether the anabolic agent teriparatide can aid in foot bone remodeling in patients with Charcot neuroarthropathy (Abstract 225).
This year’s meeting, in Boston May 16-20, has brought in a record number of accepted abstracts – 1,126 – in all areas of endocrinology. The lion’s share focuses on diabetes, thyroid disease, and bone disease. Most will be presented in Poster Viewing and Judging sessions at 10:00 a.m on Thursday for young investigators and during a poster viewing and wine and cheese reception from 4:30 p.m. to 6:30 p.m. on Friday for senior investigators.
Of note, the mother lode of clinical trials, retrospective analyses, and registry studies will be shown at the senior investigator competition on Friday evening.
That viewing session will include two post hoc analyses of data from the global SUSTAIN trial program in the investigational GLP-1 receptor agonist semaglutide. The first, Abstract 245, examines whether reductions in body weight and HbA1c differed between elderly and younger patients in SUSTAIN 7. The second, Abstract 298, is an analysis of SUSTAIN 1-5 and 7, looking at semaglutide’s effectiveness across racial and ethnic subgroups.
Another large trial, CANVAS, will be represented in two abstracts in this Friday session. In CANVAS, canagliflozin for primary prevention didn’t significantly reduce cardiovascular events in patients with at-risk type 2 diabetes, but it did so convincingly in a secondary prevention population. Outcomes by age group will be presented in Abstract 233, while those by changes in HbA1c and use of antihyperglycemic drugs will be presented in Abstract 262.
Other studies of interest in this viewing session include but are not limited to a comparison of the effects of hypnosis and certified diabetes educators on weight loss and changes in HbA1c levels (Abstract 602) and an investigation into whether the anabolic agent teriparatide can aid in foot bone remodeling in patients with Charcot neuroarthropathy (Abstract 225).
This year’s meeting, in Boston May 16-20, has brought in a record number of accepted abstracts – 1,126 – in all areas of endocrinology. The lion’s share focuses on diabetes, thyroid disease, and bone disease. Most will be presented in Poster Viewing and Judging sessions at 10:00 a.m on Thursday for young investigators and during a poster viewing and wine and cheese reception from 4:30 p.m. to 6:30 p.m. on Friday for senior investigators.
Of note, the mother lode of clinical trials, retrospective analyses, and registry studies will be shown at the senior investigator competition on Friday evening.
That viewing session will include two post hoc analyses of data from the global SUSTAIN trial program in the investigational GLP-1 receptor agonist semaglutide. The first, Abstract 245, examines whether reductions in body weight and HbA1c differed between elderly and younger patients in SUSTAIN 7. The second, Abstract 298, is an analysis of SUSTAIN 1-5 and 7, looking at semaglutide’s effectiveness across racial and ethnic subgroups.
Another large trial, CANVAS, will be represented in two abstracts in this Friday session. In CANVAS, canagliflozin for primary prevention didn’t significantly reduce cardiovascular events in patients with at-risk type 2 diabetes, but it did so convincingly in a secondary prevention population. Outcomes by age group will be presented in Abstract 233, while those by changes in HbA1c and use of antihyperglycemic drugs will be presented in Abstract 262.
Other studies of interest in this viewing session include but are not limited to a comparison of the effects of hypnosis and certified diabetes educators on weight loss and changes in HbA1c levels (Abstract 602) and an investigation into whether the anabolic agent teriparatide can aid in foot bone remodeling in patients with Charcot neuroarthropathy (Abstract 225).
FROM AACE 2018
Spine fracture risk may be increased in IBD patients
Moreover, fracture risk appears to be higher among IBD patients using steroids, according to a report published in the Journal of Clinical Gastroenterology by Yuga Komaki, MD, of the Inflammatory Bowel Disease Center, University of Chicago, and coauthors.
“Further studies addressing the differential risk among Crohn’s disease and ulcerative colitis are needed, but strict surveillance and prevention of spine fractures are indicated in IBD,” wrote Dr. Komaki and associates.
The systematic review and meta-analysis by Dr. Komaki and colleagues was based on 10 studies comprising 470,541 patients with IBD for whom the risk of fracture was reported.
“It is of importance to identify the risk of fractures, as it will increase patient morbidity, disability, and mortality,” the authors wrote. “However, it is often overlooked in the management of IBD.”
Results of the analysis by this group of researchers showed that there was no significant difference in fracture risk overall between IBD patients and controls (odds ratio, 1.08; 95% confidence interval, 0.72-1.62; P = .70).
By contrast, the OR for spine fractures was significantly elevated (OR, 2.21; 95% CI, 1.39-3.50; P less than .0001), while risk of hip, rib, and wrist fractures were not, Dr. Komaki and coauthors said in their report.
Steroids were more often being used in the treatment of IBD patients who had fractures than in patients with no fractures, though the finding did not quite reach statistical significance (OR, 1.47; 95% CI, 0.99-2.20; P = .057).
Prior studies of fracture risk in IBD have shown “controversial results,” according to Dr. Komaki and colleagues. Some of those studies suggest an increased risk of fractures, whereas others suggest the risk is not different from what is seen in the general population.
“Individual studies may be underpowered to detect any risk,” they said in the report.
Steroids have been shown to increase risk of spine and rib fracture, but whether those earlier studies apply in IBD is unclear, they noted.
While the present meta-analysis sheds light on fracture risk in IBD patients, further meta-analyses may be needed to specifically look at cohorts of patients with Crohn’s disease and ulcerative colitis.
In this study, the investigators did find that spine fracture risk was significantly elevated in patients with Crohn’s disease, and was trending toward significance for ulcerative colitis patients. They cautioned that those results were based on a limited amount of patient data.
Dr. Komaki reported that he had no disclosures related to the reported study. One study coauthor reported disclosures related to AbbVie and Celltrion.
SOURCE: Komaki Y et al. J Clin Gastroenterol. 2018 Apr 18. 2018 Apr 18. doi: 10.1097/MCG.0000000000001031.
Moreover, fracture risk appears to be higher among IBD patients using steroids, according to a report published in the Journal of Clinical Gastroenterology by Yuga Komaki, MD, of the Inflammatory Bowel Disease Center, University of Chicago, and coauthors.
“Further studies addressing the differential risk among Crohn’s disease and ulcerative colitis are needed, but strict surveillance and prevention of spine fractures are indicated in IBD,” wrote Dr. Komaki and associates.
The systematic review and meta-analysis by Dr. Komaki and colleagues was based on 10 studies comprising 470,541 patients with IBD for whom the risk of fracture was reported.
“It is of importance to identify the risk of fractures, as it will increase patient morbidity, disability, and mortality,” the authors wrote. “However, it is often overlooked in the management of IBD.”
Results of the analysis by this group of researchers showed that there was no significant difference in fracture risk overall between IBD patients and controls (odds ratio, 1.08; 95% confidence interval, 0.72-1.62; P = .70).
By contrast, the OR for spine fractures was significantly elevated (OR, 2.21; 95% CI, 1.39-3.50; P less than .0001), while risk of hip, rib, and wrist fractures were not, Dr. Komaki and coauthors said in their report.
Steroids were more often being used in the treatment of IBD patients who had fractures than in patients with no fractures, though the finding did not quite reach statistical significance (OR, 1.47; 95% CI, 0.99-2.20; P = .057).
Prior studies of fracture risk in IBD have shown “controversial results,” according to Dr. Komaki and colleagues. Some of those studies suggest an increased risk of fractures, whereas others suggest the risk is not different from what is seen in the general population.
“Individual studies may be underpowered to detect any risk,” they said in the report.
Steroids have been shown to increase risk of spine and rib fracture, but whether those earlier studies apply in IBD is unclear, they noted.
While the present meta-analysis sheds light on fracture risk in IBD patients, further meta-analyses may be needed to specifically look at cohorts of patients with Crohn’s disease and ulcerative colitis.
In this study, the investigators did find that spine fracture risk was significantly elevated in patients with Crohn’s disease, and was trending toward significance for ulcerative colitis patients. They cautioned that those results were based on a limited amount of patient data.
Dr. Komaki reported that he had no disclosures related to the reported study. One study coauthor reported disclosures related to AbbVie and Celltrion.
SOURCE: Komaki Y et al. J Clin Gastroenterol. 2018 Apr 18. 2018 Apr 18. doi: 10.1097/MCG.0000000000001031.
Moreover, fracture risk appears to be higher among IBD patients using steroids, according to a report published in the Journal of Clinical Gastroenterology by Yuga Komaki, MD, of the Inflammatory Bowel Disease Center, University of Chicago, and coauthors.
“Further studies addressing the differential risk among Crohn’s disease and ulcerative colitis are needed, but strict surveillance and prevention of spine fractures are indicated in IBD,” wrote Dr. Komaki and associates.
The systematic review and meta-analysis by Dr. Komaki and colleagues was based on 10 studies comprising 470,541 patients with IBD for whom the risk of fracture was reported.
“It is of importance to identify the risk of fractures, as it will increase patient morbidity, disability, and mortality,” the authors wrote. “However, it is often overlooked in the management of IBD.”
Results of the analysis by this group of researchers showed that there was no significant difference in fracture risk overall between IBD patients and controls (odds ratio, 1.08; 95% confidence interval, 0.72-1.62; P = .70).
By contrast, the OR for spine fractures was significantly elevated (OR, 2.21; 95% CI, 1.39-3.50; P less than .0001), while risk of hip, rib, and wrist fractures were not, Dr. Komaki and coauthors said in their report.
Steroids were more often being used in the treatment of IBD patients who had fractures than in patients with no fractures, though the finding did not quite reach statistical significance (OR, 1.47; 95% CI, 0.99-2.20; P = .057).
Prior studies of fracture risk in IBD have shown “controversial results,” according to Dr. Komaki and colleagues. Some of those studies suggest an increased risk of fractures, whereas others suggest the risk is not different from what is seen in the general population.
“Individual studies may be underpowered to detect any risk,” they said in the report.
Steroids have been shown to increase risk of spine and rib fracture, but whether those earlier studies apply in IBD is unclear, they noted.
While the present meta-analysis sheds light on fracture risk in IBD patients, further meta-analyses may be needed to specifically look at cohorts of patients with Crohn’s disease and ulcerative colitis.
In this study, the investigators did find that spine fracture risk was significantly elevated in patients with Crohn’s disease, and was trending toward significance for ulcerative colitis patients. They cautioned that those results were based on a limited amount of patient data.
Dr. Komaki reported that he had no disclosures related to the reported study. One study coauthor reported disclosures related to AbbVie and Celltrion.
SOURCE: Komaki Y et al. J Clin Gastroenterol. 2018 Apr 18. 2018 Apr 18. doi: 10.1097/MCG.0000000000001031.
FROM THE JOURNAL OF CLINICAL GASTROENTEROLOGY
Key clinical point: Patients with inflammatory bowel disease may be at increased risk of fractures in the spine.
Major finding: The odds ratio for spine fractures was 2.21 (95% CI, 1.39-3.50; P less than .0001).
Study details: A systematic review and meta-analysis of 10 studies including 470,541 patients.
Disclosures: One study author reported disclosures related to AbbVie and Celltrion.
Source: Komaki Y et al. J Clin Gastroenterol. 2018 Apr 18. doi: 10.1097/MCG.0000000000001031.
Transgender women on HT have lower bone density, more fat mass than men
CHICAGO – according to findings from a recent Brazilian study.
“Lumbar spine density was lower than in reference men but similar to that of reference women,” said Tayane Muniz Fighera, MD, speaking at the annual meeting of the Endocrine Society.
Lower lumbar spine density in transgender women was associated with lower appendicular lean mass and higher total fat mass, with correlation coefficients of 0.327 and 0.334, respectively (P = .0001 for both).
Dr. Fighera and her colleagues looked at the independent contribution of age, estradiol level, appendicular lean mass, and fat mass to bone mineral density (BMD) in the transgender patients, using linear regression analysis. Total fat mass and appendicular lean mass were both independent predictors of bone mineral density (P = .001 and P = .022, respectively). For femur BMD, age, and total fat mass were predictors (P = .001 and P = .000, respectively).
The study aimed to assess bone mineral density as well as other aspects of body composition within a cohort of transgender women initiating hormone therapy in order to determine how estrogen therapy affected BMD and assess the prevalence of low bone mass among this population.
The hypothesis, said Dr. Fighera, was that hormone therapy for transgender women might decrease muscle mass and increase fat mass, “leading to less bone surface strain and smaller bone size over time,” said Dr. Fighera, of the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Previous work has shown conflicting results, she said. “While some studies report that estrogen therapy is able to increase bone mass, others have observed no difference in BMD” despite the use of hormone therapy. The studies showing an association between estrogen therapy and decreased bone mass were those that followed patients for longer periods of time – 2 years or longer, she said.
Dr. Fighera explained that in Brazil, individuals with gender dysphoria have free access to hormone therapy and gender-affirming surgery through the public health service.
A total of 142 transgender women enrolled in the study, conducted at outpatient endocrine clinics for transgender people in Porto Alegre, Brazil. The clinics’ standardized hormone therapy protocol used daily estradiol valerate 1-4 mg, daily conjugated equine estrogen 0.625-2.5 mg, or daily transdermal 17 beta estradiol 0.5-2 mg. The estrogen therapy was accompanied by either spironolactone 50-150 mg per day, or cyproterone acetate 50-100 mg per day.
For comparison, the investigators enrolled 22 men and 17 women aged 18-40 years. All participants received a dual-energy x-ray absorptiometry (DXA) scan 3 months after those in the transgender arm began hormone therapy, and a second scan at 12 months. For the first year, participants were seen for clinical evaluation and lab studies every 3 months; they were seen every 6 months thereafter.
Although ranges were wide, estradiol levels in transgender women were, on average, approximately intermediate between the female and male control values. Total testosterone for transgender women was an average 1.17 nmol/L, closer to female (0.79 nmol/L) than male (16.39 nmol/L) values.
In a subgroup of 46 participants, Dr. Fighera and her colleagues also examined change over time for transgender women who remained on hormone therapy. Though they did find that appendicular lean mass declined and total fat mass increased from baseline, these changes in body composition were not associated with significant decreases in any BMD measurement when the DXA scan was repeated at 31 months.
Participants’ mean age was 33.7 years, and the mean BMI was 25.4 kg/m2. One-third of participants had already undergone gender-affirming surgery , and most (86.6%) had some previous exposure to hormone therapy. Almost all (96%) of study participants were white.
At 18%, “the prevalence of low bone mass for age was fairly high in this sample of [transgender women] from southern Brazil,” said Dr. Fighera. She called for more work to track change over time in hormone therapy–related bone loss for transgender women. “Until then, monitoring of bone mass should be considered in this population; nonpharmacological lifestyle-related strategies for preventing bone loss may benefit transgender women” who receive long-term hormone therapy, she said.
None of the study authors had disclosures to report.
SOURCE: Fighera T et al. ENDO 2018, Abstract OR 25-5.
CHICAGO – according to findings from a recent Brazilian study.
“Lumbar spine density was lower than in reference men but similar to that of reference women,” said Tayane Muniz Fighera, MD, speaking at the annual meeting of the Endocrine Society.
Lower lumbar spine density in transgender women was associated with lower appendicular lean mass and higher total fat mass, with correlation coefficients of 0.327 and 0.334, respectively (P = .0001 for both).
Dr. Fighera and her colleagues looked at the independent contribution of age, estradiol level, appendicular lean mass, and fat mass to bone mineral density (BMD) in the transgender patients, using linear regression analysis. Total fat mass and appendicular lean mass were both independent predictors of bone mineral density (P = .001 and P = .022, respectively). For femur BMD, age, and total fat mass were predictors (P = .001 and P = .000, respectively).
The study aimed to assess bone mineral density as well as other aspects of body composition within a cohort of transgender women initiating hormone therapy in order to determine how estrogen therapy affected BMD and assess the prevalence of low bone mass among this population.
The hypothesis, said Dr. Fighera, was that hormone therapy for transgender women might decrease muscle mass and increase fat mass, “leading to less bone surface strain and smaller bone size over time,” said Dr. Fighera, of the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Previous work has shown conflicting results, she said. “While some studies report that estrogen therapy is able to increase bone mass, others have observed no difference in BMD” despite the use of hormone therapy. The studies showing an association between estrogen therapy and decreased bone mass were those that followed patients for longer periods of time – 2 years or longer, she said.
Dr. Fighera explained that in Brazil, individuals with gender dysphoria have free access to hormone therapy and gender-affirming surgery through the public health service.
A total of 142 transgender women enrolled in the study, conducted at outpatient endocrine clinics for transgender people in Porto Alegre, Brazil. The clinics’ standardized hormone therapy protocol used daily estradiol valerate 1-4 mg, daily conjugated equine estrogen 0.625-2.5 mg, or daily transdermal 17 beta estradiol 0.5-2 mg. The estrogen therapy was accompanied by either spironolactone 50-150 mg per day, or cyproterone acetate 50-100 mg per day.
For comparison, the investigators enrolled 22 men and 17 women aged 18-40 years. All participants received a dual-energy x-ray absorptiometry (DXA) scan 3 months after those in the transgender arm began hormone therapy, and a second scan at 12 months. For the first year, participants were seen for clinical evaluation and lab studies every 3 months; they were seen every 6 months thereafter.
Although ranges were wide, estradiol levels in transgender women were, on average, approximately intermediate between the female and male control values. Total testosterone for transgender women was an average 1.17 nmol/L, closer to female (0.79 nmol/L) than male (16.39 nmol/L) values.
In a subgroup of 46 participants, Dr. Fighera and her colleagues also examined change over time for transgender women who remained on hormone therapy. Though they did find that appendicular lean mass declined and total fat mass increased from baseline, these changes in body composition were not associated with significant decreases in any BMD measurement when the DXA scan was repeated at 31 months.
Participants’ mean age was 33.7 years, and the mean BMI was 25.4 kg/m2. One-third of participants had already undergone gender-affirming surgery , and most (86.6%) had some previous exposure to hormone therapy. Almost all (96%) of study participants were white.
At 18%, “the prevalence of low bone mass for age was fairly high in this sample of [transgender women] from southern Brazil,” said Dr. Fighera. She called for more work to track change over time in hormone therapy–related bone loss for transgender women. “Until then, monitoring of bone mass should be considered in this population; nonpharmacological lifestyle-related strategies for preventing bone loss may benefit transgender women” who receive long-term hormone therapy, she said.
None of the study authors had disclosures to report.
SOURCE: Fighera T et al. ENDO 2018, Abstract OR 25-5.
CHICAGO – according to findings from a recent Brazilian study.
“Lumbar spine density was lower than in reference men but similar to that of reference women,” said Tayane Muniz Fighera, MD, speaking at the annual meeting of the Endocrine Society.
Lower lumbar spine density in transgender women was associated with lower appendicular lean mass and higher total fat mass, with correlation coefficients of 0.327 and 0.334, respectively (P = .0001 for both).
Dr. Fighera and her colleagues looked at the independent contribution of age, estradiol level, appendicular lean mass, and fat mass to bone mineral density (BMD) in the transgender patients, using linear regression analysis. Total fat mass and appendicular lean mass were both independent predictors of bone mineral density (P = .001 and P = .022, respectively). For femur BMD, age, and total fat mass were predictors (P = .001 and P = .000, respectively).
The study aimed to assess bone mineral density as well as other aspects of body composition within a cohort of transgender women initiating hormone therapy in order to determine how estrogen therapy affected BMD and assess the prevalence of low bone mass among this population.
The hypothesis, said Dr. Fighera, was that hormone therapy for transgender women might decrease muscle mass and increase fat mass, “leading to less bone surface strain and smaller bone size over time,” said Dr. Fighera, of the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Previous work has shown conflicting results, she said. “While some studies report that estrogen therapy is able to increase bone mass, others have observed no difference in BMD” despite the use of hormone therapy. The studies showing an association between estrogen therapy and decreased bone mass were those that followed patients for longer periods of time – 2 years or longer, she said.
Dr. Fighera explained that in Brazil, individuals with gender dysphoria have free access to hormone therapy and gender-affirming surgery through the public health service.
A total of 142 transgender women enrolled in the study, conducted at outpatient endocrine clinics for transgender people in Porto Alegre, Brazil. The clinics’ standardized hormone therapy protocol used daily estradiol valerate 1-4 mg, daily conjugated equine estrogen 0.625-2.5 mg, or daily transdermal 17 beta estradiol 0.5-2 mg. The estrogen therapy was accompanied by either spironolactone 50-150 mg per day, or cyproterone acetate 50-100 mg per day.
For comparison, the investigators enrolled 22 men and 17 women aged 18-40 years. All participants received a dual-energy x-ray absorptiometry (DXA) scan 3 months after those in the transgender arm began hormone therapy, and a second scan at 12 months. For the first year, participants were seen for clinical evaluation and lab studies every 3 months; they were seen every 6 months thereafter.
Although ranges were wide, estradiol levels in transgender women were, on average, approximately intermediate between the female and male control values. Total testosterone for transgender women was an average 1.17 nmol/L, closer to female (0.79 nmol/L) than male (16.39 nmol/L) values.
In a subgroup of 46 participants, Dr. Fighera and her colleagues also examined change over time for transgender women who remained on hormone therapy. Though they did find that appendicular lean mass declined and total fat mass increased from baseline, these changes in body composition were not associated with significant decreases in any BMD measurement when the DXA scan was repeated at 31 months.
Participants’ mean age was 33.7 years, and the mean BMI was 25.4 kg/m2. One-third of participants had already undergone gender-affirming surgery , and most (86.6%) had some previous exposure to hormone therapy. Almost all (96%) of study participants were white.
At 18%, “the prevalence of low bone mass for age was fairly high in this sample of [transgender women] from southern Brazil,” said Dr. Fighera. She called for more work to track change over time in hormone therapy–related bone loss for transgender women. “Until then, monitoring of bone mass should be considered in this population; nonpharmacological lifestyle-related strategies for preventing bone loss may benefit transgender women” who receive long-term hormone therapy, she said.
None of the study authors had disclosures to report.
SOURCE: Fighera T et al. ENDO 2018, Abstract OR 25-5.
REPORTING FROM ENDO 2018
Key clinical point: Transgender women on hormone therapy have bone mass more similar to women than men.
Major finding: Lower lumbar spine density was associated with higher total fat mass (P = .001).
Study details: Study of 142 transgender women receiving hormone therapy, tracked over time and compared with 22 men and 17 women for reference.
Disclosures: The study was sponsored by the Brazilian government. The authors reported that they have no conflicts of interest.
Source: Fighera T et al. ENDO 2018, Abstract OR 25-5.
European Commission expands denosumab indication
The , making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.
The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.
During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.
The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.
The , making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.
The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.
During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.
The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.
The , making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.
The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.
During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.
The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.
2017 Update on bone health
Bone health remains one of the most important health care concerns in the United States today. In 2004, the Surgeon General released a report on bone health and osteoporosis. According to the report’s introduction:
This first-ever Surgeon General’s Report on bone health and osteoporosis illustrates the large burden that bone disease places on our Nation and its citizens. Like other chronic diseases that disproportionately affect the elderly, the prevalence of bone disease and fractures is projected to increase markedly as the population ages. If these predictions come true, bone disease and fractures will have a tremendous negative impact on the future well-being of Americans. But as this report makes clear, they need not come true: by working together we can change the picture of aging in America. Osteoporosis and fractures…no longer should be thought of as an inevitable part of growing old. By focusing on prevention and lifestyle changes, including physical activity and nutrition, as well as early diagnosis and appropriate treatment, Americans can avoid much of the damaging impact of bone disease.1
Related article:
2016 Update on bone health
Although men also experience osteoporosis as they age, in women the rapid loss of bone at menopause makes their disease burden much greater. As women’s health care providers, we stand at the front line for preventing, diagnosing, and treating osteoporosis to reduce the impact of this disease. In this Update I focus on important information that has emerged in the past year.
Read about new ACP guidelines to assess fracture risk
Guidelines for therapy: How to assess fracture risk and when to treat
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
A crucial component for good bone health maintenance and osteoporotic fracture prevention is understanding the current guidelines for therapy. The most recent practice bulletin of the American College of Obstetricians and Gynecologists (ACOG) on osteoporosis was published in 2012. ACOG states that treatment be recommended for women who have a bone mineral density (BMD) T-score of -2.5 or lower.
For women in the low bone mass category (T-score between -1 and -2.5), use of the Fracture Risk Assessment Tool (FRAX) calculator can assist in making an informed treatment decision.2 Based on the FRAX calculator, women who have a 10-year risk of major osteoporotic fracture of 20% or greater, or a risk of hip fracture of 3% or greater, are candidates for pharmacologic therapy.
Women who have experienced a low-trauma fracture (especially of the vertebra or hip) also are candidates for treatment, even in the absence of osteoporosis on a dual-energy x-ray absorptiometry (DXA) report.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Updated recommendations from the ACP
The 2017 guideline published by the American College of Physicians (ACP), whose target audience is "all clinicians," recommends that, for women who have known osteoporosis, clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures.
In addition, the ACP recommends that clinicians make the decision whether or not to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. This may seem somewhat contradictory to ACOG's guidance vis-a-vis women younger than 65 years of age.
The ACP further states that given the limited evidence supporting the benefit of treatment, the balance of benefits and harms in treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T-score between -1.0 and -1.5) will benefit less than women who are 65 years of age or older with severe osteopenia (T-score <-2.0).
Risk factors and risk assessment tools
Clinicians can use their own judgment based on risk factors for fracture (lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, corticosteroid use), or they can use a risk assessment tool. Several risk assessment tools, such as the FRAX calculator mentioned earlier, are available to predict fracture risk among untreated people with low bone density. Although the FRAX calculator is widely used, there is no evidence from randomized controlled trials demonstrating a benefit of fracture reduction when FRAX scores are used in treatment decision making.
Duration of therapy. The ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. Bone density monitoring is not recommended during the 5-year treatment period for osteoporosis in women; current evidence does not show any benefit for bone density monitoring during treatment.
Moderate-quality evidence demonstrated that women treated with antiresorptive therapies (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures, even if no increase in BMD occurred or if BMD decreased.
As before, all women with osteoporosis or a previous low-trauma fracture should be treated. Use of the FRAX calculator should involve clinician judgment, and other risk factors should be taken into account. For most women, treatment should be continued for 5 years. There is no benefit in continued bone mass assessment (DXA testing) while a patient is on pharmacologic therapy.
Read about fracture risk after stopping HT
Another WHI update: No increase in fractures after stopping HT
Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.
The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.
Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
Details of the study
Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.
Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.
No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).
Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.
Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."
Read about reassessing FRAX scores
A new look at fracture risk assessment scores
Gourlay ML, Overman RA, Fine JP, et al; Women's Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-e23.
Jiang X, Gruner M, Trémollieres F, et al. Diagnostic accuracy of FRAX in predicting the 10-year risk of osteoporotic fractures using the USA treatment thresholds: a systematic review and meta-analysis. Bone. 2017;99:20-25.
The FRAX score has become a popular form of triage for women who do not yet meet the bone mass criteria of osteoporosis. Current practice guidelines recommend use of fracture risk scores for screening and pharmacologic therapeutic decision making. Some newer data, however, may give rise to questions about its utility, especially in younger women.
Fracture risk analysis in a large postmenopausal population
Gourlay and colleagues conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores. Study participants were postmenopausal women aged 50 years and older who had not previously received pharmacologic treatment and had not had a first hip or clinical vertebral facture.
Details of the study
In 54,280 postmenopausal women aged 50 to 64 years who did not have a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because the incidence of treatment-level scores was rare.
A total of 6,096 women had FRAX scores calculated with bone mineral density testing. In this group, the estimated unadjusted time to treatment-level FRAX scores was 7.6 years (95% CI, 6.6-8.7) for those aged 65 to 69, and 5.1 years (95% CI, 3.5-7.5) for women aged 75 to 79 at baseline.
Of 17,967 women aged 50 to 64 who had a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Age is key factor. Gourlay and colleagues concluded that postmenopausal women who had subthreshold fracture risk scores at baseline would be unlikely to develop a treatment-level FRAX score between ages 50 and 64. The increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture after age 65, however, supports more frequent consideration of FRAX assessment and bone mineral density testing.
Related article:
2015 Update on osteoporosis
Meta-analysis of FRAX tool accuracy
In another study, Jiang and colleagues conducted a systematic review and meta-analysis to determine how the FRAX score performed in predicting the 10-year risk of major osteoporotic fractures and hip fractures. The investigators used the US treatment thresholds.
Details of the study
Seven studies (n = 57,027) were analyzed to assess the diagnostic accuracy of FRAX in predicting major osteoporotic fractures; 20% was used as the 10-year fracture risk threshold for intervention. The mean sensitivity and specificity, along with their 95% CIs, were 10.25% (3.76%-25.06%) and 97.02% (91.17%-99.03%), respectively.
For hip fracture prediction, 6 studies (n = 50,944) were analyzed, and 3% was used as the 10-year fracture risk threshold. The mean sensitivity and specificity, along with their 95% CIs, were 45.70% (24.88%-68.13%) and 84.70% (76.41%-90.44%), respectively.
Predictive value of FRAX. The authors concluded that, using the 10-year intervention thresholds of 20% for major osteoporotic fracture and 3% for hip fracture, FRAX performed better in identifying individuals who will not have a major osteoporotic fracture or hip fracture within 10 years than in identifying those who will experience a fracture. A substantial number of those who developed fractures, especially major osteoporotic fracture within 10 years of follow up, were missed by the baseline FRAX assessment.
Increasing age is still arguably among the most important factors for decreasing bone health. Older women are more likely to develop treatment-level FRAX scores more quickly than younger women. In addition, the FRAX tool is better in predicting which women will not develop a fracture in the next 10 years than in predicting those who will experience a fracture.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- United States Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General. Rockville, Maryland: Office of the Surgeon General (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK45513/. Accessed November 6, 2017.
- Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom. FRAX Fracture Risk Assessment Tool website. www.sheffield.ac.uk/FRAX. Accessed November 6, 2017.
- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004;103(3):440–446.
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York
University School of Medicine, and Director of Gynecologic Ultrasound and Co-
Director of Bone Densitometry and Body Composition at New York University Medical
Center in New York, New York. He serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York
University School of Medicine, and Director of Gynecologic Ultrasound and Co-
Director of Bone Densitometry and Body Composition at New York University Medical
Center in New York, New York. He serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York
University School of Medicine, and Director of Gynecologic Ultrasound and Co-
Director of Bone Densitometry and Body Composition at New York University Medical
Center in New York, New York. He serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article
Bone health remains one of the most important health care concerns in the United States today. In 2004, the Surgeon General released a report on bone health and osteoporosis. According to the report’s introduction:
This first-ever Surgeon General’s Report on bone health and osteoporosis illustrates the large burden that bone disease places on our Nation and its citizens. Like other chronic diseases that disproportionately affect the elderly, the prevalence of bone disease and fractures is projected to increase markedly as the population ages. If these predictions come true, bone disease and fractures will have a tremendous negative impact on the future well-being of Americans. But as this report makes clear, they need not come true: by working together we can change the picture of aging in America. Osteoporosis and fractures…no longer should be thought of as an inevitable part of growing old. By focusing on prevention and lifestyle changes, including physical activity and nutrition, as well as early diagnosis and appropriate treatment, Americans can avoid much of the damaging impact of bone disease.1
Related article:
2016 Update on bone health
Although men also experience osteoporosis as they age, in women the rapid loss of bone at menopause makes their disease burden much greater. As women’s health care providers, we stand at the front line for preventing, diagnosing, and treating osteoporosis to reduce the impact of this disease. In this Update I focus on important information that has emerged in the past year.
Read about new ACP guidelines to assess fracture risk
Guidelines for therapy: How to assess fracture risk and when to treat
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
A crucial component for good bone health maintenance and osteoporotic fracture prevention is understanding the current guidelines for therapy. The most recent practice bulletin of the American College of Obstetricians and Gynecologists (ACOG) on osteoporosis was published in 2012. ACOG states that treatment be recommended for women who have a bone mineral density (BMD) T-score of -2.5 or lower.
For women in the low bone mass category (T-score between -1 and -2.5), use of the Fracture Risk Assessment Tool (FRAX) calculator can assist in making an informed treatment decision.2 Based on the FRAX calculator, women who have a 10-year risk of major osteoporotic fracture of 20% or greater, or a risk of hip fracture of 3% or greater, are candidates for pharmacologic therapy.
Women who have experienced a low-trauma fracture (especially of the vertebra or hip) also are candidates for treatment, even in the absence of osteoporosis on a dual-energy x-ray absorptiometry (DXA) report.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Updated recommendations from the ACP
The 2017 guideline published by the American College of Physicians (ACP), whose target audience is "all clinicians," recommends that, for women who have known osteoporosis, clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures.
In addition, the ACP recommends that clinicians make the decision whether or not to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. This may seem somewhat contradictory to ACOG's guidance vis-a-vis women younger than 65 years of age.
The ACP further states that given the limited evidence supporting the benefit of treatment, the balance of benefits and harms in treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T-score between -1.0 and -1.5) will benefit less than women who are 65 years of age or older with severe osteopenia (T-score <-2.0).
Risk factors and risk assessment tools
Clinicians can use their own judgment based on risk factors for fracture (lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, corticosteroid use), or they can use a risk assessment tool. Several risk assessment tools, such as the FRAX calculator mentioned earlier, are available to predict fracture risk among untreated people with low bone density. Although the FRAX calculator is widely used, there is no evidence from randomized controlled trials demonstrating a benefit of fracture reduction when FRAX scores are used in treatment decision making.
Duration of therapy. The ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. Bone density monitoring is not recommended during the 5-year treatment period for osteoporosis in women; current evidence does not show any benefit for bone density monitoring during treatment.
Moderate-quality evidence demonstrated that women treated with antiresorptive therapies (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures, even if no increase in BMD occurred or if BMD decreased.
As before, all women with osteoporosis or a previous low-trauma fracture should be treated. Use of the FRAX calculator should involve clinician judgment, and other risk factors should be taken into account. For most women, treatment should be continued for 5 years. There is no benefit in continued bone mass assessment (DXA testing) while a patient is on pharmacologic therapy.
Read about fracture risk after stopping HT
Another WHI update: No increase in fractures after stopping HT
Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.
The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.
Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
Details of the study
Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.
Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.
No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).
Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.
Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."
Read about reassessing FRAX scores
A new look at fracture risk assessment scores
Gourlay ML, Overman RA, Fine JP, et al; Women's Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-e23.
Jiang X, Gruner M, Trémollieres F, et al. Diagnostic accuracy of FRAX in predicting the 10-year risk of osteoporotic fractures using the USA treatment thresholds: a systematic review and meta-analysis. Bone. 2017;99:20-25.
The FRAX score has become a popular form of triage for women who do not yet meet the bone mass criteria of osteoporosis. Current practice guidelines recommend use of fracture risk scores for screening and pharmacologic therapeutic decision making. Some newer data, however, may give rise to questions about its utility, especially in younger women.
Fracture risk analysis in a large postmenopausal population
Gourlay and colleagues conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores. Study participants were postmenopausal women aged 50 years and older who had not previously received pharmacologic treatment and had not had a first hip or clinical vertebral facture.
Details of the study
In 54,280 postmenopausal women aged 50 to 64 years who did not have a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because the incidence of treatment-level scores was rare.
A total of 6,096 women had FRAX scores calculated with bone mineral density testing. In this group, the estimated unadjusted time to treatment-level FRAX scores was 7.6 years (95% CI, 6.6-8.7) for those aged 65 to 69, and 5.1 years (95% CI, 3.5-7.5) for women aged 75 to 79 at baseline.
Of 17,967 women aged 50 to 64 who had a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Age is key factor. Gourlay and colleagues concluded that postmenopausal women who had subthreshold fracture risk scores at baseline would be unlikely to develop a treatment-level FRAX score between ages 50 and 64. The increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture after age 65, however, supports more frequent consideration of FRAX assessment and bone mineral density testing.
Related article:
2015 Update on osteoporosis
Meta-analysis of FRAX tool accuracy
In another study, Jiang and colleagues conducted a systematic review and meta-analysis to determine how the FRAX score performed in predicting the 10-year risk of major osteoporotic fractures and hip fractures. The investigators used the US treatment thresholds.
Details of the study
Seven studies (n = 57,027) were analyzed to assess the diagnostic accuracy of FRAX in predicting major osteoporotic fractures; 20% was used as the 10-year fracture risk threshold for intervention. The mean sensitivity and specificity, along with their 95% CIs, were 10.25% (3.76%-25.06%) and 97.02% (91.17%-99.03%), respectively.
For hip fracture prediction, 6 studies (n = 50,944) were analyzed, and 3% was used as the 10-year fracture risk threshold. The mean sensitivity and specificity, along with their 95% CIs, were 45.70% (24.88%-68.13%) and 84.70% (76.41%-90.44%), respectively.
Predictive value of FRAX. The authors concluded that, using the 10-year intervention thresholds of 20% for major osteoporotic fracture and 3% for hip fracture, FRAX performed better in identifying individuals who will not have a major osteoporotic fracture or hip fracture within 10 years than in identifying those who will experience a fracture. A substantial number of those who developed fractures, especially major osteoporotic fracture within 10 years of follow up, were missed by the baseline FRAX assessment.
Increasing age is still arguably among the most important factors for decreasing bone health. Older women are more likely to develop treatment-level FRAX scores more quickly than younger women. In addition, the FRAX tool is better in predicting which women will not develop a fracture in the next 10 years than in predicting those who will experience a fracture.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Bone health remains one of the most important health care concerns in the United States today. In 2004, the Surgeon General released a report on bone health and osteoporosis. According to the report’s introduction:
This first-ever Surgeon General’s Report on bone health and osteoporosis illustrates the large burden that bone disease places on our Nation and its citizens. Like other chronic diseases that disproportionately affect the elderly, the prevalence of bone disease and fractures is projected to increase markedly as the population ages. If these predictions come true, bone disease and fractures will have a tremendous negative impact on the future well-being of Americans. But as this report makes clear, they need not come true: by working together we can change the picture of aging in America. Osteoporosis and fractures…no longer should be thought of as an inevitable part of growing old. By focusing on prevention and lifestyle changes, including physical activity and nutrition, as well as early diagnosis and appropriate treatment, Americans can avoid much of the damaging impact of bone disease.1
Related article:
2016 Update on bone health
Although men also experience osteoporosis as they age, in women the rapid loss of bone at menopause makes their disease burden much greater. As women’s health care providers, we stand at the front line for preventing, diagnosing, and treating osteoporosis to reduce the impact of this disease. In this Update I focus on important information that has emerged in the past year.
Read about new ACP guidelines to assess fracture risk
Guidelines for therapy: How to assess fracture risk and when to treat
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
A crucial component for good bone health maintenance and osteoporotic fracture prevention is understanding the current guidelines for therapy. The most recent practice bulletin of the American College of Obstetricians and Gynecologists (ACOG) on osteoporosis was published in 2012. ACOG states that treatment be recommended for women who have a bone mineral density (BMD) T-score of -2.5 or lower.
For women in the low bone mass category (T-score between -1 and -2.5), use of the Fracture Risk Assessment Tool (FRAX) calculator can assist in making an informed treatment decision.2 Based on the FRAX calculator, women who have a 10-year risk of major osteoporotic fracture of 20% or greater, or a risk of hip fracture of 3% or greater, are candidates for pharmacologic therapy.
Women who have experienced a low-trauma fracture (especially of the vertebra or hip) also are candidates for treatment, even in the absence of osteoporosis on a dual-energy x-ray absorptiometry (DXA) report.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Updated recommendations from the ACP
The 2017 guideline published by the American College of Physicians (ACP), whose target audience is "all clinicians," recommends that, for women who have known osteoporosis, clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures.
In addition, the ACP recommends that clinicians make the decision whether or not to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. This may seem somewhat contradictory to ACOG's guidance vis-a-vis women younger than 65 years of age.
The ACP further states that given the limited evidence supporting the benefit of treatment, the balance of benefits and harms in treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T-score between -1.0 and -1.5) will benefit less than women who are 65 years of age or older with severe osteopenia (T-score <-2.0).
Risk factors and risk assessment tools
Clinicians can use their own judgment based on risk factors for fracture (lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, corticosteroid use), or they can use a risk assessment tool. Several risk assessment tools, such as the FRAX calculator mentioned earlier, are available to predict fracture risk among untreated people with low bone density. Although the FRAX calculator is widely used, there is no evidence from randomized controlled trials demonstrating a benefit of fracture reduction when FRAX scores are used in treatment decision making.
Duration of therapy. The ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. Bone density monitoring is not recommended during the 5-year treatment period for osteoporosis in women; current evidence does not show any benefit for bone density monitoring during treatment.
Moderate-quality evidence demonstrated that women treated with antiresorptive therapies (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures, even if no increase in BMD occurred or if BMD decreased.
As before, all women with osteoporosis or a previous low-trauma fracture should be treated. Use of the FRAX calculator should involve clinician judgment, and other risk factors should be taken into account. For most women, treatment should be continued for 5 years. There is no benefit in continued bone mass assessment (DXA testing) while a patient is on pharmacologic therapy.
Read about fracture risk after stopping HT
Another WHI update: No increase in fractures after stopping HT
Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.
The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.
Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
Details of the study
Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.
Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.
No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).
Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.
Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."
Read about reassessing FRAX scores
A new look at fracture risk assessment scores
Gourlay ML, Overman RA, Fine JP, et al; Women's Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-e23.
Jiang X, Gruner M, Trémollieres F, et al. Diagnostic accuracy of FRAX in predicting the 10-year risk of osteoporotic fractures using the USA treatment thresholds: a systematic review and meta-analysis. Bone. 2017;99:20-25.
The FRAX score has become a popular form of triage for women who do not yet meet the bone mass criteria of osteoporosis. Current practice guidelines recommend use of fracture risk scores for screening and pharmacologic therapeutic decision making. Some newer data, however, may give rise to questions about its utility, especially in younger women.
Fracture risk analysis in a large postmenopausal population
Gourlay and colleagues conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores. Study participants were postmenopausal women aged 50 years and older who had not previously received pharmacologic treatment and had not had a first hip or clinical vertebral facture.
Details of the study
In 54,280 postmenopausal women aged 50 to 64 years who did not have a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because the incidence of treatment-level scores was rare.
A total of 6,096 women had FRAX scores calculated with bone mineral density testing. In this group, the estimated unadjusted time to treatment-level FRAX scores was 7.6 years (95% CI, 6.6-8.7) for those aged 65 to 69, and 5.1 years (95% CI, 3.5-7.5) for women aged 75 to 79 at baseline.
Of 17,967 women aged 50 to 64 who had a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Age is key factor. Gourlay and colleagues concluded that postmenopausal women who had subthreshold fracture risk scores at baseline would be unlikely to develop a treatment-level FRAX score between ages 50 and 64. The increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture after age 65, however, supports more frequent consideration of FRAX assessment and bone mineral density testing.
Related article:
2015 Update on osteoporosis
Meta-analysis of FRAX tool accuracy
In another study, Jiang and colleagues conducted a systematic review and meta-analysis to determine how the FRAX score performed in predicting the 10-year risk of major osteoporotic fractures and hip fractures. The investigators used the US treatment thresholds.
Details of the study
Seven studies (n = 57,027) were analyzed to assess the diagnostic accuracy of FRAX in predicting major osteoporotic fractures; 20% was used as the 10-year fracture risk threshold for intervention. The mean sensitivity and specificity, along with their 95% CIs, were 10.25% (3.76%-25.06%) and 97.02% (91.17%-99.03%), respectively.
For hip fracture prediction, 6 studies (n = 50,944) were analyzed, and 3% was used as the 10-year fracture risk threshold. The mean sensitivity and specificity, along with their 95% CIs, were 45.70% (24.88%-68.13%) and 84.70% (76.41%-90.44%), respectively.
Predictive value of FRAX. The authors concluded that, using the 10-year intervention thresholds of 20% for major osteoporotic fracture and 3% for hip fracture, FRAX performed better in identifying individuals who will not have a major osteoporotic fracture or hip fracture within 10 years than in identifying those who will experience a fracture. A substantial number of those who developed fractures, especially major osteoporotic fracture within 10 years of follow up, were missed by the baseline FRAX assessment.
Increasing age is still arguably among the most important factors for decreasing bone health. Older women are more likely to develop treatment-level FRAX scores more quickly than younger women. In addition, the FRAX tool is better in predicting which women will not develop a fracture in the next 10 years than in predicting those who will experience a fracture.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- United States Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General. Rockville, Maryland: Office of the Surgeon General (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK45513/. Accessed November 6, 2017.
- Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom. FRAX Fracture Risk Assessment Tool website. www.sheffield.ac.uk/FRAX. Accessed November 6, 2017.
- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004;103(3):440–446.
- United States Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General. Rockville, Maryland: Office of the Surgeon General (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK45513/. Accessed November 6, 2017.
- Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom. FRAX Fracture Risk Assessment Tool website. www.sheffield.ac.uk/FRAX. Accessed November 6, 2017.
- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004;103(3):440–446.
