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Article ; Online: The Skeletal Consequences of Bariatric Surgery.

Krez, Alexandra N / Stein, Emily M

2020 Volume 18, Issue 3, Page(s) 262–272

Abstract: Purpose of review: This review outlines the recent findings regarding the impact of bariatric surgery on bone. It explores potential mechanisms for skeletal changes following bariatric surgery and strategies for management.: Recent findings: Bone ... ...

Abstract	Purpose of review: This review outlines the recent findings regarding the impact of bariatric surgery on bone. It explores potential mechanisms for skeletal changes following bariatric surgery and strategies for management. Recent findings: Bone loss following bariatric surgery is multifactorial. Probable mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Skeletal changes that occur after bariatric surgery are specific to procedure type and persist for several years post-operatively. Studies suggest that while bone loss begins early, fracture risk may be increased later in the post-operative course, particularly after Roux-en-Y gastric bypass (RYGB). Further research is needed to assess the extent to which skeletal changes following bariatric surgery result in fragility. Current management should be geared toward prevention of bone loss, correction of nutritional deficiencies, and incorporation of weight bearing exercise. Pharmacologic treatment should be considered for high-risk patients.
MeSH term(s)	Bariatric Surgery/adverse effects ; Bone Diseases, Metabolic/etiology ; Bone Diseases, Metabolic/metabolism ; Bone Diseases, Metabolic/physiopathology ; Calcium-Regulating Hormones and Agents/metabolism ; Gastrectomy/adverse effects ; Gastric Bypass/adverse effects ; Gastrointestinal Hormones/metabolism ; Humans ; Obesity/metabolism ; Obesity/surgery ; Osteoporosis/etiology ; Osteoporosis/metabolism ; Osteoporosis/physiopathology ; Osteoporotic Fractures/epidemiology ; Osteoporotic Fractures/etiology ; Postoperative Complications/etiology ; Postoperative Complications/metabolism ; Postoperative Complications/physiopathology ; Weight-Bearing
Chemical Substances	Calcium-Regulating Hormones and Agents ; Gastrointestinal Hormones
Language	English
Publishing date	2020-04-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2186581-4
ISSN	1544-2241 ; 1544-1873
ISSN (online)	1544-2241
ISSN	1544-1873
DOI	10.1007/s11914-020-00579-2
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Article ; Online: Impaired Bone Matrix: The Key to Fragility in Type 2 Diabetes?

Hernandez, Christopher J / Stein, Emily M / Donnelly, Eve

The Journal of clinical endocrinology and metabolism

2021 Volume 106, Issue 7, Page(s) e2825–e2827

MeSH term(s)	Bone Density ; Bone Matrix ; Bone and Bones ; Diabetes Mellitus, Type 2 ; Humans
Language	English
Publishing date	2021-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgab150
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Article ; Online: Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT.

Kuker, Adriana P / Agarwal, Sanchita / Shane, Elizabeth / Bicca, Juliana / Geer, Eliza B / Cremers, Serge / Dworakowski, Elzbieta / Cohen, Adi / Nickolas, Thomas L / Stein, Emily M / Freda, Pamela U

Journal of the Endocrine Society

2024 Volume 8, Issue 6, Page(s) bvae079

Abstract: Context: Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment ... ...

Abstract	Context: Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment with the GH receptor antagonist pegvisomant on bone microstructure were unknown. Methods: We studied 25 patients with acromegaly (15 men, 10 women). In 20, we evaluated areal bone mineral density (BMD) by dual-energy X-ray absorptiometry and bone turnover markers (BTMs) longitudinally, before and during pegvisomant treatment. After long-term pegvisomant in 17, we cross-sectionally assessed volumetric BMD, microarchitecture, stiffness, and failure load of the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HRpQCT) and compared these results to those of healthy controls and 2 comparison groups of nonpegvisomant-treated acromegaly patients, remission, and active disease, matched for other therapies and characteristics. Results: In the longitudinal study, areal BMD improved at the lumbar spine but decreased at the hip in men after a median ∼7 years of pegvisomant. In the cross-sectional study, patients on a median ∼9 years of pegvisomant had significantly larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to healthy controls. Microstructure was similar in the pegvisomant and acromegaly comparison groups. BTMs were lowered, then stable over time. Conclusion: In this, the first study to examine bone microstructure in pegvisomant-treated acromegaly, we found deficits in volumetric BMD and microarchitecture of the peripheral skeleton. BTM levels remained stable with long-term therapy. Deficits in bone quality identified by HRpQCT may play a role in the pathogenesis of fragility in treated acromegaly.
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvae079
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Article ; Online: The Skeletal Effects of Inhaled Glucocorticoids.

Sutter, Stephanie A / Stein, Emily M

Current osteoporosis reports

2016 Volume 14, Issue 3, Page(s) 106–113

Abstract: The skeletal effects of inhaled glucocorticoids are poorly understood. Children with asthma treated with inhaled glucocorticoids have lower growth velocity, bone density, and adult height. Studies of adults with asthma have reported variable effects on ... ...

Abstract	The skeletal effects of inhaled glucocorticoids are poorly understood. Children with asthma treated with inhaled glucocorticoids have lower growth velocity, bone density, and adult height. Studies of adults with asthma have reported variable effects on BMD, although prospective studies have demonstrated bone loss after initiation of inhaled glucocorticoids in premenopausal women. There is a dose-response relationship between inhaled glucocorticoids and fracture risk in asthmatics; the risk of vertebral and non-vertebral fractures is greater in subjects treated with the highest doses in the majority of studies. Patients with COPD have lower BMD and higher fracture rates compared to controls, however, the majority of studies have not found an additional detrimental effect of inhaled glucocorticoids on bone. While the evidence is not conclusive, it supports using the lowest possible dose of inhaled glucocorticoids to treat patients with asthma and COPD and highlights the need for further research on this topic.
MeSH term(s)	Administration, Inhalation ; Adult ; Asthma/drug therapy ; Body Height ; Bone Density ; Bone Development ; Child ; Dose-Response Relationship, Drug ; Fractures, Bone/epidemiology ; Glucocorticoids/administration & dosage ; Humans ; Osteoporosis/epidemiology ; Pulmonary Disease, Chronic Obstructive/drug therapy
Chemical Substances	Glucocorticoids
Language	English
Publishing date	2016-04-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2186581-4
ISSN	1544-2241 ; 1544-1873
ISSN (online)	1544-2241
ISSN	1544-1873
DOI	10.1007/s11914-016-0308-1
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Article ; Online: Glucocorticoid-induced osteonecrosis in systemic lupus erythematosus patients.

Kaneko, Kaichi / Chen, Hao / Kaufman, Matthew / Sverdlov, Isaak / Stein, Emily M / Park-Min, Kyung-Hyun

Clinical and translational medicine

2021 Volume 11, Issue 10, Page(s) e526

Abstract: Osteonecrosis (ON) is a complex and multifactorial complication of systemic lupus erythematosus (SLE). ON is a devastating condition that causes severe pain and compromises the quality of life. The prevalence of ON in SLE patients is variable, ranging ... ...

Abstract	Osteonecrosis (ON) is a complex and multifactorial complication of systemic lupus erythematosus (SLE). ON is a devastating condition that causes severe pain and compromises the quality of life. The prevalence of ON in SLE patients is variable, ranging from 1.7% to 52%. However, the pathophysiology and risk factors for ON in patients with SLE have not yet been fully determined. Several mechanisms for SLE patients' propensity to develop ON have been proposed. Glucocorticoid is a widely used therapeutic option for SLE patients and high-dose glucocorticoid therapy in SLE patients is strongly associated with the development of ON. Although the hips and knees are the most commonly affected areas, it may be present at multiple anatomical locations. Clinically, ON often remains undetected until patients feel discomfort and pain at specific sites at which point the process of bone death is already advanced. However, strategies for prevention and options for treatment are limited. Here, we review the epidemiology, risk factors, diagnosis, and treatment options for glucocorticoid-induced ON, with a specific focus on patients with SLE.
MeSH term(s)	Glucocorticoids/adverse effects ; Humans ; Lupus Erythematosus, Systemic/complications ; Osteonecrosis/chemically induced ; Osteonecrosis/complications
Chemical Substances	Glucocorticoids
Language	English
Publishing date	2021-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2697013-2
ISSN	2001-1326 ; 2001-1326
ISSN (online)	2001-1326
ISSN	2001-1326
DOI	10.1002/ctm2.526
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Article: Clinical Characteristics and Fracture Patterns Among Postmenopausal Women with Isolated Osteoporosis at the Forearm.

Chukir, Tariq / Haseltine, Katherine / Do, Huong / McMahon, Donald J / Russell, Linda / Stein, Emily M

Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry

2021 Volume 25, Issue 2, Page(s) 208–214

Abstract: Patients found to have isolated osteoporosis at the 1/3 radius (1/3RO) represent a therapeutic dilemma. It is unknown whether 1/3RO is associated with an increased risk of fragility fractures, and is therefore unclear whether these patients should be ... ...

Abstract	Patients found to have isolated osteoporosis at the 1/3 radius (1/3RO) represent a therapeutic dilemma. It is unknown whether 1/3RO is associated with an increased risk of fragility fractures, and is therefore unclear whether these patients should be treated similarly to those with osteoporosis at central sites. This retrospective study investigated the clinical significance of 1/3RO by comparing medical history, fracture prevalence, areal BMD, and Trabecular Bone Score in postmenopausal women with 1/3RO (n = 107) to age-matched women with osteoporosis at the hip and/or spine (PMO, n = 214), and to controls without osteoporosis at any site (n = 214). We then compared the clinical and densitometric characteristics among women with 1/3RO according to fracture history. The mean age of the 535 women included in the study was 71 ± 8 yr. Women with 1/3RO had BMD in the osteopenic range at all other sites (mean spine T-score = -1.0, total hip = -1.4, femoral neck = -1.7). Women with 1/3RO reported similar calcium and vitamin D intake, prevalence of primary hyperparathyroidism, chronic kidney disease, and other comorbidities compared to the other groups. The prevalence of an osteoporotic fracture of the spine, hip, wrist, or humerus tended to be higher among women with PMO compared to 1/3RO or controls (PMO: 31%, 1/3RO: 21%, Controls: 23%, p = 0.07). Among women with 1/3RO, fracture prevalence was related to older age. No other clinical characteristic distinguished women with and without fracture. Neither BMD at other sites nor TBS differed according to fracture history. Among postmenopausal women with 1/3RO, those who are older are at an increased risk of fracture, even when T-scores at other sites are well above the osteoporosis threshold. Additional research is needed to confirm our results, and to assess whether treatment should be considered to reduce fracture risk in older women with 1/3RO.
MeSH term(s)	Absorptiometry, Photon/methods ; Aged ; Bone Density ; Female ; Forearm ; Humans ; Male ; Osteoporosis/complications ; Osteoporosis/diagnostic imaging ; Osteoporosis/epidemiology ; Osteoporosis, Postmenopausal/complications ; Osteoporosis, Postmenopausal/diagnostic imaging ; Osteoporosis, Postmenopausal/epidemiology ; Osteoporotic Fractures/epidemiology ; Osteoporotic Fractures/etiology ; Postmenopause ; Retrospective Studies
Language	English
Publishing date	2021-08-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2040951-5
ISSN	1094-6950
ISSN	1094-6950
DOI	10.1016/j.jocd.2021.07.012
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Article ; Online: The Effect of TNF Inhibition on Bone Density and Fracture Risk and of IL17 Inhibition on Radiographic Progression and Bone Density in Patients with Axial Spondyloarthritis: a Systematic Literature Review.

Ashany, Dalit / Stein, Emily M / Goto, Rie / Goodman, Susan M

Current rheumatology reports

2019 Volume 21, Issue 5, Page(s) 20

Abstract: Purpose of review: Osteoporosis in axial spondyloarthritis may be modified by therapy. The purpose of this systematic review is to describe (i) the effect of TNFi on BMD, (ii) the effect of secukinumab on BMD, and (iii) the effect of secukinumab on ... ...

Abstract	Purpose of review: Osteoporosis in axial spondyloarthritis may be modified by therapy. The purpose of this systematic review is to describe (i) the effect of TNFi on BMD, (ii) the effect of secukinumab on BMD, and (iii) the effect of secukinumab on radiographic disease progression in axSpA. Recent findings: We searched PubMed, Embase, and Cochrane using the following retrieval languages: spondyloarthritis, ankylosing spondylitis, TNF, IL-17, x-rays, and osteoporosis. Twenty-nine studies were included; 27 re: TNFi and BMD, and 2 re: IL-17 blockers and x-ray progression. TNFi over 2-4 years increased BMD of the lumbar spine (3.2-14.9%) and hip (2.26-4.7%) without reducing vertebral fractures. Secukinumab reduced radiographic progression; none (73%) and minimal (79%) at 4 years. No data on IL-17 blockade and bone were found. TNFi therapy improves bone density but not vertebral fracture rates. Secukinumab improves symptoms and may slow radiographic progression. Data is lacking regarding the effects of secukinumab on BMD and fractures. These are important questions which may impact the choice of therapy.
MeSH term(s)	Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/therapeutic use ; Biological Products/administration & dosage ; Biological Products/adverse effects ; Biological Products/therapeutic use ; Bone Density/drug effects ; Disease Progression ; Fractures, Bone/etiology ; Humans ; Interleukin-17/antagonists & inhibitors ; Risk Factors ; Spondylarthritis/drug therapy ; Tumor Necrosis Factor Inhibitors/administration & dosage ; Tumor Necrosis Factor Inhibitors/adverse effects ; Tumor Necrosis Factor Inhibitors/therapeutic use
Chemical Substances	Antirheumatic Agents ; Biological Products ; Interleukin-17 ; Tumor Necrosis Factor Inhibitors
Language	English
Publishing date	2019-03-12
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	2057357-1
ISSN	1534-6307 ; 1523-3774
ISSN (online)	1534-6307
ISSN	1523-3774
DOI	10.1007/s11926-019-0818-9
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Article ; Online: Bone loss after bariatric surgery: causes, consequences, and management.

Stein, Emily M / Silverberg, Shonni J

The lancet. Diabetes & endocrinology

2014 Volume 2, Issue 2, Page(s) 165–174

Abstract: Bariatric surgery is an effective and increasingly common treatment for severe obesity and its many comorbidities. The side-effects of bariatric surgery can include detrimental effects on bone and mineral metabolism. Bone disease in patients who have had ...

Abstract	Bariatric surgery is an effective and increasingly common treatment for severe obesity and its many comorbidities. The side-effects of bariatric surgery can include detrimental effects on bone and mineral metabolism. Bone disease in patients who have had bariatric surgery is affected by preoperative abnormalities in bone and mineral metabolism related to severe obesity. Changes that arise after bariatric surgery are specific to procedure type: the most pronounced abnormalities in calciotropic hormones and bone loss are noted after procedures that result in the most malabsorption. The most consistent site for bone loss after all bariatric procedures is at the hip. There are limitations of dual-energy x-ray absorptiometry technology in this population, including artefact introduced by adipose tissue itself. Bone loss after bariatric surgery is probably multifactorial. Proposed mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Few data for fracture risk in the bariatric population are available, and this is a crucial area for additional research. Treatment should be geared toward correction of nutritional deficiencies and study of bone mineral density in high-risk patients. We explore the skeletal response to bariatric surgery, potential mechanisms for changes, and strategies for management.
MeSH term(s)	Bariatric Surgery/adverse effects ; Bone Density ; Bone Resorption/drug therapy ; Bone Resorption/etiology ; Humans ; Malnutrition/complications ; Malnutrition/drug therapy ; Weight Loss
Language	English
Publishing date	2014-02-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(13)70183-9
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Article ; Online: Persistent Deficits in Bone Quality in Treated Acromegaly: Evidence From Assessments of Microstructure.

Kuker, Adriana P / Agarwal, Sanchita / Shane, Elizabeth / Cohen, Adi / Nickolas, Thomas L / Stein, Emily M / Reid, Tirissa J / Hans, Didier / Cremers, Serge / Bruce, Jeffrey N / Freda, Pamela U

Journal of the Endocrine Society

2023 Volume 7, Issue 10, Page(s) bvad121

Abstract: Purpose: Fractures are increased in patients with acromegaly, both before and after successful acromegaly treatment. Abnormalities of bone microstructure, which may underlie this fragility, are present in active acromegaly but to what extent these ... ...

Abstract	Purpose: Fractures are increased in patients with acromegaly, both before and after successful acromegaly treatment. Abnormalities of bone microstructure, which may underlie this fragility, are present in active acromegaly but to what extent these improve with acromegaly treatment or persist despite biochemical remission remains unclear. To examine these questions, we studied the effects of acromegaly treatment and remission on bone quality. Methods: Sixty-five women and men with acromegaly were studied. Subgroups underwent assessments of areal bone mineral density by dual x-ray absorptiometry, trabecular bone score (TBS), and volumetric bone mineral density, microarchitecture, stiffness and failure load of the distal radius and tibia by high-resolution peripheral quantitative tomography in a longitudinal study before and after acromegaly treatment and in a cross-sectional study in which patients were compared to sex-, age-, and body mass index-matched healthy controls. Results: In the longitudinal study, significant increases in total, cortical, and trabecular densities at the radius and tibia and increased stiffness and failure load of the tibia occurred with acromegaly treatment. In the cross-sectional study, patients in biochemical remission after surgery had larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to controls. TBS did not change with acromegaly treatment but correlated with some microstructural parameters. Conclusion: We show, for the first time, that volumetric bone mineral density and microarchitecture of the peripheral skeleton improve with acromegaly treatment but remain abnormal in patients in remission after surgery compared to controls. These abnormalities, known to be associated with fractures in other populations, may play a role in the pathogenesis of persistent fragility in treated acromegaly.
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvad121
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Article ; Online: Opportunistic Evaluation of Trabecular Bone Texture by MRI Reflects Bone Mineral Density and Microarchitecture.

Heilbronner, Alison K / Koff, Matthew F / Breighner, Ryan / Kim, Han Jo / Cunningham, Matthew / Lebl, Darren R / Dash, Alexander / Clare, Shannon / Blumberg, Olivia / Zaworski, Caroline / McMahon, Donald J / Nieves, Jeri W / Stein, Emily M

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 8, Page(s) e557–e566

Abstract: Context: Many individuals at high risk for fracture are never evaluated for osteoporosis and subsequently do not receive necessary treatment. Utilization of magnetic resonance imaging (MRI) is burgeoning, providing an ideal opportunity to use MRI to ... ...

Abstract	Context: Many individuals at high risk for fracture are never evaluated for osteoporosis and subsequently do not receive necessary treatment. Utilization of magnetic resonance imaging (MRI) is burgeoning, providing an ideal opportunity to use MRI to identify individuals with skeletal deficits. We previously reported that MRI-based bone texture was more heterogeneous in postmenopausal women with a history of fracture compared to controls. Objective: The present study aimed to identify the microstructural characteristics that underlie trabecular texture features. Methods: In a prospective cohort, we measured spine volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT), peripheral vBMD and microarchitecture by high-resolution peripheral QCT (HRpQCT), and areal BMD (aBMD) by dual-energy x-ray absorptiometry. Vertebral trabecular bone texture was analyzed using T1-weighted MRIs. A gray level co-occurrence matrix was used to characterize the distribution and spatial organization of voxelar intensities and derive the following texture features: contrast (variability), entropy (disorder), angular second moment (ASM; uniformity), and inverse difference moment (IDM; local homogeneity). Results: Among 46 patients (mean age 64, 54% women), lower peripheral vBMD and worse trabecular microarchitecture by HRpQCT were associated with greater texture heterogeneity by MRI-higher contrast and entropy (r ∼ -0.3 to 0.4, P < .05), lower ASM and IDM (r ∼ +0.3 to 0.4, P < .05). Lower spine vBMD by QCT was associated with higher contrast and entropy (r ∼ -0.5, P < .001), lower ASM and IDM (r ∼ +0.5, P < .001). Relationships with aBMD were less pronounced. Conclusion: MRI-based measurements of trabecular bone texture relate to vBMD and microarchitecture, suggesting that this method reflects underlying microstructural properties of trabecular bone. Further investigation is required to validate this methodology, which could greatly improve identification of patients with skeletal fragility.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Bone Density ; Cancellous Bone/diagnostic imaging ; Prospective Studies ; Absorptiometry, Photon/methods ; Fractures, Bone ; Bone Diseases, Metabolic ; Magnetic Resonance Imaging
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad082
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