Type 2 diabetes alters bone composition after menopause
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Postmenopausal women with type 2 diabetes have increased bone mineral content and lower bone turnover markers vs. those with normal or impaired glucose tolerance, according to data published in the Journal of Bone and Mineral Research.
“Despite having normal to elevated bone density — which should predict uncompromised bone strength — individuals with type 2 diabetes are at increased risk of fracture compared to those with normal glucose tolerance,” Kendall F. Moseley, MD, assistant professor of medicine in the division of endocrinology, diabetes and metabolism at Johns Hopkins University School of Medicine, and Eve Donnelly, PhD, associate professor in the department of materials science and engineering at Cornell University, told Healio. “Our research demonstrates that there are complex alterations in bone mineral properties with worsening glycemic control as well as reduced bone resorption/formation that may contribute to the increased fracture risk seen in those with type 2 diabetes.”
Moseley, Donnelly and colleagues analyzed bone and glycemic data from 85 women at least 5 years postmenopause. Researchers ruled out osteoporosis with a bone mineral density screening by DXA. Participants also underwent a 2-hour 75 g oral glucose tolerance test and an iliac crest bone biopsy, which was evaluated using Fourier transform infrared imaging. Participants were divided into three groups based on OGTT: a normal glucose tolerance group with values less than 140 mg/dL (n = 35), an IGT cohort with glucose of 140 mg/dL to 199 mg/dL (n = 26) and a group with type 2 diabetes prescribed insulin (n = 25).
The diabetes group had greater bone mineral content compared with the other groups. In the cortical bone, the mean mineral matrix value was 7% higher (P = .0108) and the mineral matrix distribution was 10% narrower (P = .0469) in the diabetes vs. the normal glucose tolerance group. The cortical acid phosphate content distribution width was 14% narrower in the diabetes vs. the normal glucose (P = .0045) and impaired glucose groups (P = .0048). Similarly, the trabecular acid phosphate content distribution was 11% narrower for the diabetes group vs. the normal glucose cohort (P = .0126) and 10% narrower vs. the impaired glucose group (P = .0489).
Mean values of crystallinity in cortical bone were similar between groups, but among those with diabetes, the cortical crystallinity distribution was 16% wider (P = .0195) and trabecular crystallinity distribution was 14% wider vs. the normal glucose group (P = .036).
In addition, the diabetes group had lower bone turnover markers vs. the normal glucose group, with 31% lower C-terminal telopeptide of type 1 collagen (CTX-1; P = .043), 25% lower undercarboxylated osteocalcin (P = .027) and 25% lower procollagen type 1 N-terminal propeptide (P1NP; P = 0.014); P1NP was 24% lower vs. the impaired glucose tolerance group (P = .013).
“To date, screening for fracture risk and initiation of osteoporosis treatment are based on BMD measurements. However, older adults with type 2 diabetes fracture despite normal BMD, indicating compromised bone quality,” Moseley and Donnelly said. “We have demonstrated that there are altered bone tissue and mineral properties as well as reduced bone turnover — parameters of bone quality not captured on DXA — in type 2 diabetes, potentially contributing to compromised bone strength in this population. Understanding additional parameters of bone strength that may be compromised in type 2 diabetes will help us do the following in this complicated population: modify screening, recommend preventive strategies, prescribe rationally and develop new therapeutic interventions.”
For more information:
Eve Donnelly, PhD, can be reached at eve.donnelly@cornell.edu.
Kendall F. Moseley, MD, can be reached at kmosele4@jhmi.edu.
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In addition to the well-recognized complications of type 2 diabetes, increased fractures occur. The reasons are unclear, as type 2 diabetes is associated with osteoprotective factors: increased bone mineral density and decreased turnover. Whether fractures result from bone tissue changes from glycemia is unknown.
Here, iliac-crest bone biopsies from postmenopausal women with normoglycemia, impaired-glycemia and type 2 diabetes were analyzed by Fourier-transform infrared imaging, a spectroscopic technique that analyzes compositional bone properties. Women with type 2 diabetes vs. normoglycemia had greater tissue mineral content, or greater mineral accumulation over time; less heterogeneous distribution of mineral content, or a narrower range of tissue ages; and decreases in a marker of new mineral formation, acid phosphatase. Thus, in type 2 diabetes, as secondary mineralization progressed with reduced turnover, tissue mineral content increased and the distribution of compositional properties narrowed, changes consistent with older tissue. However, women with type 2 diabetes also had a wider distribution of crystal size and trabecular collagen that was less mature and more heterogenous, suggesting that younger bone tissue was also present. Findings for women with impaired-glycemia throughout were between women with type 2 diabetes and normoglycemia.
This study helps us unravel diabetic bone fragility. It shows that progressive alteration of bone tissue composition occurs with glycemia, leading to predominantly older and more mineralized, but also younger and less mature, bone tissue. Future work will test how this affects mechanical behavior and fractures.
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