DURHAM, NC — Diabetes mellitus among older men has been associated with increased bone mineral density but paradoxically increased fracture risk, according to a study in the Journal of Bone and Mineral Research.1

The mechanisms behind that remain unclear, however, according to research led by the Durham, NC, VAMC and Duke University. The team sought to determine the interactions among medication treatment, glycemic control and diabetes-associated comorbidities.

To do that, the researchers conducted a retrospective study including 652,901 male veterans 65 and older with diabetes and baseline hemoglobin A1c (HbA1c) values. Participants all received primary care at the VHA from 2000 to 2010.

The study used administrative data , including ICD9 diagnoses and pharmacy records, and linked those to Medicare fee-for-service data. At the same time, the authors calculated hazard ratios for any clinical fracture and hip fracture using competing risk hazards models, adjusted for fracture risk factors including age, race/ethnicity, BMI, alcohol and tobacco use, rheumatoid arthritis, corticosteroid use, as well as diabetes-related comorbidities including cardiovascular disease, chronic kidney disease, and peripheral neuropathy.

Results indicated that HbA1c lower than 6.5% was associated with a higher risk of any clinical fracture [HR 1.08 (95%CI: 1.06-1.11)], compared to the reference HbA1c of 7.5-8.5%. Fracture risk was not increased among those with A1c of 8.5% or among those with A1c 6.5-7.5%.

“Use of insulin was independently associated with greater risk of fracture (HR 1.10, 95% CI: 1.07-1.12),” researchers explained. “There was a significant interaction between insulin use and HbA1c level, (P < 0.001), such that those using insulin with HbA1c < 6.5% had HR 1.23 and those with HbA1c 6.5-7.5% had HR 1.15.”

On the other hand, the study determined that metformin use was associated with decreased fracture risk (HR 0.88, 95% CI: 0.87-0.90).

“We conclude that among older men with diabetes, those with HbA1c lower than 6.5% are at increased risk for any clinical and hip fracture,” the authors wrote. “Insulin use is associated with higher fracture risk, especially among those with tight glycemic control. Our findings demonstrate the importance of the treatment regimen and avoiding hypoglycemia for fracture prevention in older men with diabetes.”

  1. Lee RH, Sloane R, Pieper C, Lyles KW, Adler RA, Van Houtven C, LaFleur J, Colón-Emeric C. Glycemic control and insulin treatment alter fracture risk in older men with Type 2 diabetes mellitus. J Bone Miner Res. 2019 Jul 3. doi: 10.1002/jbmr.3826. [Epub ahead of print] PubMed PMID: 31269274.