A paradoxical increased fracture and mortality risk seen among people with type 2 diabetes (T2D) despite high bone mineral density (BMD) may be explained by bone quality, research from the Garvan Institute of Medical Research in Sydney suggests.

People with T2D had a higher mortality following a fracture than people without diabetes an analysis of data from more than 3500 people enrolled in the long-running Dubbo Osteoporosis Epidemiology Study found.

In a comparison of 265 people with T2D at baseline (average duration six years) and 3303 without, those with diabetes had a greater number of baseline or prior fractures (19.6% vs 14.0%) which were predominantly clinical vertebral fractures.

The higher number of fractures was evident despite people with T2D having significantly higher BMD at the lumbar spine (1.22 vs 1.13g/cm2) and femoral neck (0.91 vs 0.85g/cm2). The higher BMD was likely due to higher BMI (29.7 vs 26.4 kg/m2), said the study authors, led by endocrinologist Dr Angela Sheu.

Speaking at the Australian Diabetes Congress in Adelaide on 22 August, Dr Sheu said it was surprising the analysis found no difference in incident on-study fractures. However, when compared to those without T2D or fracture, mortality was significantly increased in those with T2D and fracture (HR 2.30 in women and HR 2.72 in men), when adjusted for comorbidities.

In a separate subset analysis of 525 people enrolled in the Dubbo Osteoporosis Epidemiology Study, the researchers showed that BMD was lowest in the group of lean, insulin-sensitive individuals, when compared to people with obesity, with or without insulin resistance or T2D.

Notably, levels of bone turnover markers such as osteocalcin (OC), procollagen type 1 N-propeptide  (P1NP) and collagen type 1 crosslinked C terminal telopeptide (CTx) were lowest only in people with T2D compared with the other groups.

Speaking to the limbic, Dr Sheu said the findings suggested that impaired bone turnover and thus bone quality may contribute to excess fracture risk in people with T2D, despite them having relatively preserved BMD.

“This adds to the evidence that patients with metabolic risk factors may have impaired bone health. And the mechanism may be related to visceral adiposity and insulin resistance, not just obesity per se.

“So even though people with type 2 diabetes have normal bone density, they may have reduced bone quality and be at an increased risk of fracture. Since each fracture increases mortality in this group of already vulnerable patients, managing bone health in our patients with T2D is vital,” she said.

However Dr Sheu said it was too early to say whether there were implications for osteoporosis screening or preventive treatment for people with type 2 diabetes and future studies looking at these questions should be performed.