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Increased fracture risk also found in type 2 diabetes

Issue: October 2015

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In addition to its role in HCV, skeletal fragility is now recognized as a complication of type 2 diabetes. Adults with type 2 diabetes are at increased risk for fractures despite having normal or increased bone mineral density compared with age- and weight-matched peers without diabetes, according to experts.

“These individuals may not fulfill a T-score–driven definition of osteoporosis; however, they experience skeletal failure, the hallmark of osteoporosis,” Kendall F. Moseley, MD, assistant professor of medicine in the division of endocrinology, diabetes and metabolism at Johns Hopkins Hospital in Baltimore, told Endocrine Today.

Higher risk

Several studies attest to a higher fracture risk associated with type 2 diabetes: 20% higher at any site among postmenopausal women with diabetes vs. those without the disease, in the Women’s Health Initiative Observational Study; 64% higher in men and women with type 2 diabetes in the Health, Aging, and Body Composition Study. Meta-analyses have shown men and women with type 2 diabetes to have double to triple the risk for hip fracture, according to Moseley.

Disease severity and duration also affect risk. “In the Singapore Chinese Health Study, while participants with [type 2 diabetes] for even 5 years duration were at risk for hip fracture (RR = 1.4), those with disease for longer than 15 years were at markedly higher hip fracture risk (RR = 2.66) compared with those without disease,” Moseley said.

The higher risk for fractures, paradoxically, is not associated with lower BMD. In a meta-analysis of data from three prospective observational studies, Schwartz and colleagues found a higher fracture risk for a given T-score or Fracture Risk Algorithm (FRAX) score among older adults with type 2 diabetes compared with patients without diabetes.

“Thus, established methods for predicting fractures, such as BMD and FRAX, may not adequately reflect the risk in patients with [type 2 diabetes],” Matthew P. Gilbert, DO, MPH, associate professor of medicine in the division of endocrinology and diabetes at University of Vermont College of Medicine, told Endocrine Today. “The increase in bone fragility in patients with [type 2 diabetes] is ... more closely related to bone quality than bone quantity.”

Bone quality

Bone remodeling processes may be compromised in people with diabetes and may account for the high bone density–high fracture risk paradox, according to Gilbert. “Alterations in bone formation and resorption in patients with [type 2 diabetes] can slow the rate of bone loss and cause a higher BMD than expected for their age. The reduction in bone turnover can also increase bone fragility, independent of BMD,” he said.

Moseley agrees. “A number of studies have looked beyond bone mass in [type 2 diabetes] and highlighted intrinsic skeletal changes that likely compromise bone strength,” she said. These changes include increased cortical porosity in diabetic bone observed with high-resolution quantitative computed tomography and reduced material strength at the tibia in postmenopausal women with diabetes revealed by microindentation testing.

Also, higher levels of circulating sclerostin in patients with type 2 diabetes have been associated with increased disease duration and HbA1c levels, but decreased bone turnover biomarkers, which may suggest that elevated sclerostin levels increase bone fragility by worsening bone quality independent of BMD in patients with type 2 diabetes, according to Gilbert.

Questions remain

The mechanisms by which type 2 diabetes increases skeletal fragility are still under investigation. Candidates include effects of diabetes medications and complications, such as neuropathy and chronic kidney disease, obesity, hyperglycemia, oxidative stress and accumulation of advanced glycation end-products that contribute to altered bone metabolism, structure and strength, according to Gilbert.

Still, “fracture risk in [type 2 diabetes] persists in cohort analyses controlling for these factors, suggesting that glycemic derangement itself detrimentally alters bone,” Moseley said. “Additional research is needed to identify the underpinnings of skeletal failure in [type 2 diabetes] and to prevent and treat the fractures lurking on the horizon.” – by Jill Rollet

• References:
• Bonds DE, et al. J Clin Endocrinol Metab. 2006;91:3404-3410.
• Gennari L, et al. J Clin Endocrinol Metab. 2012;doi:10.1210/jc.2011-2958.
• Koh WP, et al. Diabetes Care. 2010;doi:10.2337/dc10-0067.
• Rico H, et al. Calcif Tissue Int. 1989;45:71-73.
• Schwartz AV, et al. J Bone Miner Res. 2005;20:596-603.
• Schwartz AV, et al. JAMA. 2011;doi:10.1001/jama.2011.715.

• Winkler DG, et al. EMBO J. 2003;22:6267-6276.
• For more information:
• Matthew P. Gilbert, DO, MPH, can be reached at Endocrinology and Diabetes Clinic, 62 Tilley Drive, Suite 202, South Burlington, VT 05403; email: Matthew.Gilbert@uvmhealth.org.
• Kendall F. Moseley, MD, can be reached at Johns Hopkins Bayview Metabolic Bone Center, 5200 Eastern Ave., Baltimore, MD 21224; email: kmosele4@jhmi.edu.

Disclosures: Gilbert and Moseley report no relevant financial disclosures.