Common Osteoporosis Treatment May Reduce Risk of Incident Diabetes

Denosumab may reduce the risk of developing diabetes, according to the results of a recent study published in JAMA Network Open. Patients with osteoporosis who continued through 2 doses of denosumab had significantly lower risk of incident diabetes compared to patients who did not continue treatment following the initial dose.

“These findings may help physicians choose an appropriate antiosteoporosis medication for patients with osteoporosis while also considering a medication associated with lowering diabetes risk,” wrote authors in the paper.

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Denosumab is a humanized monoclonal antibody against receptor activator of nuclear factor κBligand (RANKL) used to treat osteoporosis, a condition associated with reduced bone mineral density and strength. Osteoporosis affects many older adults around the world.

A growing body of research highlights a link between bone health and glucose metabolism.Diabetes can exacerbate bone fragility and other increased risks among patients with osteoporosis, so preventing diabetes might not only be beneficial for metabolic health, but also for bone health.

Investigators in Taiwan conducted a large-scale nationwide, propensity score–matched cohort study to evaluate the efficacy of denosumab in reducing the incidence of diabetes in patients with osteoporosis.

The study included 68510 Taiwanese participants (mean [SD] age, 77.7 [9.8] years; 57,762 [84.3%] female). Investigators evaluated 34,255 patients who started denosumab treatment and continued with it as well as 34,255 who started denosumab treatment but discontinued it after the initial dose. Participants received follow-up at 1.9 years, on average.

In the 2-dose arm, 2016 patients developed diabetes compared to 3220 participants who developed diabetes in the comparison (1-dose) arm (incidence rate, 35.9 vs 43.6 per 1000 person-years), showing that continued denosumab treatment could reduce the risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90) more than a single dose.

In addition, adults aged 65 years and older were especially more likely to reap the benefits of denosumab if they received 2 doses compared to an initial dose alone, according to the results of an age-stratified analysis (HR, 0.80; 95% CI, 0.75-0.85). Treatment was also shown to reduce the risk of incident diabetes in both males and females (HR, 0.85; 95% CI, 0.73-0.97 and HR, 0.81; 95% CI, 0.76-0.86, respectively). Co-morbidities did affect its ability to reduce the risk of diabetes.

There is no concrete explanation as to why denosumab reduces the risk of diabetes, althoughprevious research suggests that reducing RANKL can reduce inflammation associated with diabetes and insulin resistance. The loss of β-cell replication may also be associated with diabetes, so using agents that work against RANKL may promote β-cell proliferation and reduce diabetes risk.

Limitations of the study include using claims-based data; having remaining residual confounding factors and differential censoring; making an indirect evaluation of incident diabetes; and producing findings that may not be generalizable to other races, ethnicities, or countries.

“This study provides a fundamental backdrop for future prospective studies or randomized clinical trials to validate the findings on denosumab use and its association with reduced diabetes risk,” authors wrote.

REFERENCE

Huang H, Chuang AT, Liao T, et al. Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis. JAMA Netw Open. 2024;7(2):e2354734. doi:10.1001/jamanetworkopen.2023.54734