Diabetes underestimated as a fracture risk factor

Bone health

By Tony James

26 Aug 2015

Diabetes is a significant risk factor for minimal trauma fractures but its impact is not fully recognised in clinical practice, Professor Peter Ebeling told delegates at the ESA-SRB meeting here in Adelaide.

Professor Ebeling, chair of the Division of Medicine at Monash Health in Melbourne and immediate past president of the ESA, explained to the limbic that diabetes is now being considered for inclusion in the FRAX fracture risk calculator.

“In type 1 diabetes, which often has its onset during the acquisition of peak bone mass, there is a six-fold increase in fracture risk,” Professor Ebeling said. “The main effect is due to insulin deficiency, which leads to decreased bone formation, low rates of bone modelling and remodelling, and low bone density.”

In contrast, BMD is often increased type 2 diabetes but fracture risk is doubled because of reduced bone quality and increased fragility resulting from the effects of advanced glycation end-products (AGEs) on non-enzymatic collagen cross-linking.

“Serum levels of one of these AGEs, pentosidine, are associated with an increased risk of vertebral fractures in postmenopausal women with diabetes, independent of BMD,” he said. “We need better measures of bone quality, perhaps through imaging the microarchitecture or biochemical assessment of AGEs like pentosidine.”

Even though BMD may not be decreased, there is no reason to expect that existing treatments for osteoporosis will not be effective after a minimal trauma fracture, he said. Such a fracture fulfils the PBS criteria for osteoporosis therapy regardless of BMD.

Diabetes treatments also influence bone quality. Pioglitazone decreases bone formation and promotes bone loss and osteoporotic fractures in postmenopausal women, while the GLP-1 agonists decrease bone resorption and increase BMD and DPP-4 inhibitors are associated with decreased fracture risk and an increase in bone formation markers.

SGLT-2 inhibitors can increase fracture risk: for example, dapagliflozin does not change bone turnover markers or BMD, but is associated with an increase in fracture risk in patients with moderate renal impairment.

In both types of diabetes, complications such as low vision, diabetic nephropathy, and peripheral and autonomic neuropathy increase the risk for falls and fractures.

“Understanding the effects of diabetes has been complicated by the effects of obesity, especially in patients with type 2 diabetes,” Professor Ebeling said.

Obesity has divergent effects on fracture risk, increasing the likelihood of a humerus or ankle fracture but reducing hip, pelvis and wrist fractures.

“Risk factors for fracture in obese people appear to be similar to those in non-obese people, but patterns of falling and the effects of increased skeletal loading are particularly important in the obese,” he said.

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