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Article ; Online: Diabetes, bone and glucose-lowering agents: clinical outcomes.

Schwartz, Ann V

2017 Volume 60, Issue 7, Page(s) 1170–1179

Abstract: Older adults with diabetes are at higher risk of fracture and of complications resulting from a fracture. Hence, fracture risk reduction is an important goal in diabetes management. This review is one of a pair discussing the relationship between ... ...

Abstract	Older adults with diabetes are at higher risk of fracture and of complications resulting from a fracture. Hence, fracture risk reduction is an important goal in diabetes management. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Beata Lecka-Czernik (DOI 10.1007/s00125-017-4269-4 ). Specifically, this review discusses the challenges of accurate fracture risk assessment in diabetes. Standard tools for risk assessment can be used to predict fracture but clinicians need to be aware of the tendency for the bone mineral density T-score and the fracture risk assessment tool (FRAX) to underestimate risk in those with diabetes. Diabetes duration, complications and poor glycaemic control are useful clinical markers of increased fracture risk. Glucose-lowering agents may also affect fracture risk, independent of their effects on glycaemic control, as seen with the negative skeletal effects of the thiazolidinediones; in this review, the potential effects of glucose-lowering medications on fracture risk are discussed. Finally, the current understanding of effective fracture prevention in older adults with diabetes is reviewed.
Language	English
Publishing date	2017-07
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-017-4283-6
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Article ; Online: Efficacy of Osteoporosis Therapies in Diabetic Patients.

Schwartz, Ann V

Calcified tissue international

2017 Volume 100, Issue 2, Page(s) 165–173

Abstract: Diabetes is characterized by increased fracture risk and by reduced bone strength for a given density. Contributing factors may include lower bone turnover and accumulation of advanced glycation endproducts. There are concerns that the pharmacological ... ...

Abstract	Diabetes is characterized by increased fracture risk and by reduced bone strength for a given density. Contributing factors may include lower bone turnover and accumulation of advanced glycation endproducts. There are concerns that the pharmacological therapies for osteoporosis, particularly anti-resorptive therapies that suppress bone turnover, may not be as effective in the setting of diabetes. This review considers clinical trials and observational studies that have assessed the efficacy of anti-resorptive and anabolic therapies in diabetic patients. Post hoc analyses of randomized trials indicate that raloxifene has similar efficacy for prevention of vertebral fractures in diabetic compared with non-diabetic patients. Evidence from randomized clinical trials is lacking for anti-fracture efficacy of other osteoporosis therapies in diabetes. However, observational studies suggest that bisphosphonates are effective in preventing fractures in diabetic patients. The great majority of diabetic patients in studies to date have been type 2, and efficacy of osteoporosis therapies in type 1 diabetic patients remains to be addressed. Further evaluation of the efficacy of osteoporosis therapies in the setting of diabetes is needed to provide optimal fracture prevention for this population.
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-016-0177-8
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Zs.A 317: Show issues

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Article ; Online: MRI Assessment of Bone Marrow Composition in Osteoporosis.

Li, Xiaojuan / Schwartz, Ann V

Current osteoporosis reports

2020 Volume 18, Issue 1, Page(s) 57–66

Abstract: Purpose of review: To provide an overview on recent technical development for quantifying marrow composition using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques, as well as a summary on recent findings of interrelationship between ... ...

Abstract	Purpose of review: To provide an overview on recent technical development for quantifying marrow composition using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques, as well as a summary on recent findings of interrelationship between marrow adipose tissue (MAT) and skeletal health in the context of osteoporosis. Recent findings: There have been significant technical advances in reliable quantification of marrow composition using MR techniques. Cross-sectional studies have demonstrated a negative correlation between MAT and bone, with trabecular bone associating more strongly with MAT than cortical bone. However, longitudinal studies of MAT and bone are limited. MAT contents and composition have been associated with prevalent vertebral fracture. The evidence between MAT and clinical fracture is more limited, and, to date, no studies have reported on the relationship between MAT and incident fracture. Increasing evidence suggests a dynamic role of marrow fat in skeletal health. Reliable non-invasive quantification of marrow composition will facilitate developing novel treatment strategies for osteoporosis.
MeSH term(s)	Adipose Tissue/diagnostic imaging ; Bone Marrow/diagnostic imaging ; Cancellous Bone/diagnostic imaging ; Cortical Bone/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Osteoporosis/diagnostic imaging ; Osteoporotic Fractures ; Spinal Fractures
Language	English
Publishing date	2020-01-16
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/s11914-020-00562-x
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Zs.A 6146: Show issues

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Article ; Online: Epidemiology of fractures in type 2 diabetes.

Schwartz, Ann V

Bone

2016 Volume 82, Page(s) 2–8

Abstract: Type 2 diabetes affects an increasing proportion of older adults, the population that is also at elevated risk of fracture. Type 2 diabetes itself increases the risk of fracture, particularly in African-American and Latino populations. In Western ... ...

Abstract	Type 2 diabetes affects an increasing proportion of older adults, the population that is also at elevated risk of fracture. Type 2 diabetes itself increases the risk of fracture, particularly in African-American and Latino populations. In Western countries, overweight and obesity, associated with reduced fracture risk, are highly prevalent in diabetic patients. Studies in East Asian countries that have a lower prevalence of obesity with diabetes may help to disentangle the effects of diabetes and obesity on the skeleton. Type 2 diabetes is also associated with higher bone density, and as a result standard tools for fracture prediction tend to underestimate fracture risk in this population, an important challenge for risk assessment in the clinical setting. Contributing factors to the increased fracture risk in type 2 diabetes include more frequent falls and deficits in diabetic bone, not captured by dual X-ray absorptiometry (DXA), that are as yet not clearly understood. Recent epidemiological studies indicate that poor glycemic control contributes to increased fracture risk although intensive lowering of A1C is not effective in preventing fracture. This article is part of a Special Issue entitled "Bone and diabetes".
MeSH term(s)	Bone Density/physiology ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Fractures, Bone/diagnosis ; Fractures, Bone/epidemiology ; Humans ; Randomized Controlled Trials as Topic/methods ; Risk Factors
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2015.05.032
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Article: Marrow fat and bone: review of clinical findings.

Schwartz, Ann V

Frontiers in endocrinology

2015 Volume 6, Page(s) 40

Abstract: With growing interest in the connection between fat and bone, there has been increased investigation of the relationship with marrow fat in particular. Clinical research has been facilitated by the development of non-invasive methods to measure bone ... ...

Abstract	With growing interest in the connection between fat and bone, there has been increased investigation of the relationship with marrow fat in particular. Clinical research has been facilitated by the development of non-invasive methods to measure bone marrow fat content and composition. Studies in different populations using different measurement techniques have established that higher marrow fat is associated with lower bone density and prevalent vertebral fracture. The degree of unsaturation in marrow fat may also affect bone health. Although other fat depots tend to be strongly correlated, marrow fat has a distinct pattern, suggesting separate mechanisms of control. Longitudinal studies are limited, but are crucial to understand the direct and indirect roles of marrow fat as an influence on skeletal health. With greater appreciation of the links between bone and energy metabolism, there has been growing interest in understanding the relationship between marrow fat and bone. It is well established that levels of marrow fat are higher in older adults with osteoporosis, defined by either low bone density or vertebral fracture. However, the reasons for and implications of this association are not clear. This review focuses on clinical studies of marrow fat and its relationship to bone.
Language	English
Publishing date	2015-03-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2015.00040
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Article ; Online: More rapid bone mineral density loss in older men with diabetes: The Osteoporotic Fractures in Men (MrOS) Study.

Tramontana, Flavia / Napoli, Nicola / Litwack-Harrison, Stephanie / Bauer, Douglas C / Orwoll, Eric S / Cauley, Jane A / Strotmeyer, Elsa S / Schwartz, Ann V

The Journal of clinical endocrinology and metabolism

2024

Abstract: Context: Type 2 diabetes mellitus (T2D) is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes.: Objective: To determine whether bone loss rate is affected by diabetes status in older men, ... ...

Abstract	Context: Type 2 diabetes mellitus (T2D) is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes. Objective: To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study. Methods: The multisite MrOS study enrolled 5,994 men aged ≥65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without a follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or T2D, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with T2D were also evaluated with GLM. Results: In adjusted models, loss in hip BMD was greater in men with T2D (- 2.23%: 95% CI: -2.54 to -1.91; p<0.001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; p=0.33) compared to NG (-1.57%: 95% CI -1.73 to -1.41). Among men with T2D, TZD, insulin and sulfonylurea use were associated with greater hip BMD loss. Conclusions: Men with T2D, but not prediabetes, experienced an accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations.
Language	English
Publishing date	2024-02-26
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/dgae045
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Article: Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics.

Löffler, Maximilian T / Wu, Po-Hung / Pirmoazen, Amir M / Joseph, Gabby B / Stewart, Jay M / Saeed, Isra / Liu, Jing / Schafer, Anne L / Schwartz, Ann V / Link, Thomas M / Kazakia, Galateia J

Bone reports

2024 Volume 20, Page(s) 101745

Abstract: Introduction: Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. ...

Abstract	Introduction: Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. Methods: The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. Results: MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, Conclusions: The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.
Language	English
Publishing date	2024-02-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2821774-3
ISSN	2352-1872
ISSN	2352-1872
DOI	10.1016/j.bonr.2024.101745
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Article ; Online: Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes.

Dhaliwal, Ruban / Ewing, Susan K / Vashishth, Deepak / Semba, Richard D / Schwartz, Ann V

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2021 Volume 37, Issue 2, Page(s) 265–272

Abstract: Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), ...

Abstract	Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non-diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24-1.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94-1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. © 2021 American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Aged ; Bone Density ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Fractures, Bone/complications ; Fractures, Bone/epidemiology ; Humans ; Lysine ; Risk Factors ; Spinal Fractures/etiology
Chemical Substances	Lysine (K3Z4F929H6)
Language	English
Publishing date	2021-11-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4466
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Article ; Online: Reply to: Indications of Increased Vertebral Fracture Risk in Patients With Type 2 Diabetes.

Napoli, Nicola / Schwartz, Ann V / Black, Dennis M

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2018 Volume 33, Issue 1, Page(s) 183

MeSH term(s)	Aged ; Diabetes Mellitus, Type 2 ; Humans ; Male ; Osteoporosis ; Risk ; Spinal Fractures
Language	English
Publishing date	2018-01-03
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.3322
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Article ; Online: Diabetes Mellitus and the Benefit of Antiresorptive Therapy on Fracture Risk.

Eastell, Richard / Vittinghoff, Eric / Lui, Li-Yung / Ewing, Susan K / Schwartz, Ann V / Bauer, Douglas C / Black, Dennis M / Bouxsein, Mary L

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2022 Volume 37, Issue 11, Page(s) 2121–2131

Abstract: Type 2 diabetes (T2D) is associated with increased risk of fractures. However, it is unclear whether current osteoporosis treatments reduce fractures in individuals with diabetes. The aim of the study was to determine whether presence of T2D influences ... ...

Abstract	Type 2 diabetes (T2D) is associated with increased risk of fractures. However, it is unclear whether current osteoporosis treatments reduce fractures in individuals with diabetes. The aim of the study was to determine whether presence of T2D influences the efficacy of antiresorptive treatment for osteoporosis using the Foundation for the National Institutes of Health (FNIH)-American Society for Bone and Mineral Research (ASBMR)-Study to Advance Bone Mineral Density (BMD) as a Regulatory Endpoint (SABRE) cohort, which includes individual patient data from randomized trials of osteoporosis therapies. In this study we included 96,385 subjects, 6.8% of whom had T2D, from nine bisphosphonate trials, two selective estrogen receptor modulator (SERM) trials, two trials of menopausal hormone therapy, one denosumab trial, and one odanacatib trial. We used Cox regression to obtain the treatment hazard ratio (HR) for incident nonvertebral, hip, and all fractures and logistic regression to obtain the treatment odds ratio (OR) for incident morphometric vertebral fractures, separately for T2D and non-DM. We used linear regression to estimate the effect of treatment on 2-year change in BMD (n = 49,099) and 3-month to 12-month change in bone turnover markers (n = 12,701) by diabetes status. In all analyses, we assessed the interaction between treatment and diabetes status. In pooled analyses of all 15 trials, we found that diabetes did not impact treatment efficacy, with similar reductions in vertebral, nonvertebral, all, and hip fractures, increases in total hip and femoral neck BMD, and reductions in serum C-terminal cross-linking telopeptide (CTX), urinary N-telopeptide of type I collagen/creatinine (NTX/Cr) and procollagen type 1 N propeptide (P1NP) (all interactions p > 0.05). We found similar results for the pooled analysis of bisphosphonate trials. However, when we considered trials individually, we found a few interactions within individual studies between diabetes status and the effects of denosumab and odanacatib on fracture risk, change in BMD or bone turnover markers (BTMs). In sum, these results provide strong evidence that bisphosphonates and most licensed antiresorptive drugs are effective at reducing fracture risk and increasing BMD irrespective of diabetes status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
MeSH term(s)	Humans ; Bone Density ; Bone Density Conservation Agents/therapeutic use ; Denosumab/therapeutic use ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diphosphonates/therapeutic use ; Hip Fractures/drug therapy ; Osteoporosis/drug therapy
Chemical Substances	Bone Density Conservation Agents ; Denosumab (4EQZ6YO2HI) ; Diphosphonates ; odanacatib (N673F6W2VH)
Language	English
Publishing date	2022-10-07
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.4697
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