Spotlight on bone density

Several recent studies looked at the effects of diabetes and its treatments on bone density and fracture risk.

First, a meta-analysis published by Diabetes Care on Oct. 28 compiled 15 studies with more than 800,000 patients to assess the relationship between type 2 diabetes and vertebral fractures. It found that diabetes was associated with lower rates of prevalent vertebral fractures (odds ratio [OR], 0.84; 95% CI, 0.74 to 0.95) but increased rates of incident vertebral fractures (OR, 1.35; 95% CI, 1.27 to 1.44). The analysis also looked specifically at the studies providing individual patient data and found that patients who had both diabetes and a vertebral fracture had increased mortality risk compared to those with neither condition (hazard ratio [HR], 2.11; 95% CI, 1.72 to 2.59) and those with vertebral fracture and no diabetes (HR, 1.84; 95% CI, 1.49 to 2.28). Their increase in mortality compared to patients with only diabetes and no fracture was not statistically significant (HR, 1.23; 95% CI, 0.99 to 1.52). “Our findings give clarity to the conflicting findings observed across previous meta-analyses,” the authors said. They noted that differences might be due in part to diagnosis of asymptomatic vertebral fractures. Limitations of the study included lack of data on other comorbidities and treatments. The authors concluded that patients with type 2 diabetes should be systematically assessed for vertebral fractures and then treated accordingly.

Another study, published by Pharmacoepidemiology & Drug Safety on Oct. 24, compared the risk of fractures in patients initiating treatment with either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors. It included 30,549 matched pairs of patients who started treatment with the drug classes in 2013 to 2015. Over a median follow-up of 219 days, there were 745 fractures, with the most common site being the foot (32.7%). Overall, SGLT-2 inhibitors were associated with an insignificant increase in fracture compared to DPP-4 inhibitors (hazard ratio [HR] in the first 14 days of therapy, 1.82 [95% CI, 0.99 to 3.32]; HR on day 15 and beyond, 1.07 [95% CI, 0.92 to 1.24]; HR for the entire follow-up, 1.11 [95% CI, 0.96 to 1.28]). However, small subgroup analyses did show that fractures were increased in the first 14 days in women starting an SGLT-2 inhibitor (HR compared to women starting a DPP-4 inhibitor, 2.49 [95% CI, 1.02 to 6.05]) and in patients starting canagliflozin (HR compared to any DPP-4 inhibitor, 2.01 [95% CI, 1.00 to 4.05]). Only 46 fractures total occurred in the first 14 days, limiting the certainty of the findings. The authors speculated that the difference between drug classes might relate to volume depletion, but they noted that falls were not a common cause of fractures. Still, they suggested clinicians advise patients initiating SGLT-2 inhibitors “to take adequate remedial measures such as regular intake of water.”

Finally, a study published by the Journal of Clinical Endocrinology & Metabolism on Nov. 2 compared bone mineral density in children and adults with and without type 1 diabetes. According to dual X-ray absorptiometry of the lumbar spine, the 194 patients with type 1 diabetes did not have significantly different bone mineral density from the 156 controls. However, in the subgroup of postmenopausal women, type 1 diabetes was associated with significantly lower bone mineral density. The authors noted that female children showed an insignificant trend toward lower bone density with type 1 diabetes. They speculated that the lack of difference in other subgroups might be due to small sample size or that type 1 diabetes might be associated with higher bone loss during menopause. The study did not find any association between bone density and type 1 diabetes complications.