Denosumab use for osteoporosis may also lower risk for diabetes
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Key takeaways:
- Adults with osteoporosis who received more than one dose of denosumab had a reduced risk for developing diabetes.
- A lower risk for diabetes with denosumab was observed only among adults aged 65 years and older.
Adults with osteoporosis who received a full course of denosumab were less likely to develop incident diabetes than those who discontinued denosumab after the initial dose, according to study data published in JAMA Network Open.
“While we were hopeful about the metabolic effects of denosumab (Prolia, Amgen) based on preclinical studies, seeing a clear association with reduced diabetes risk in a nationwide, large-scale, real-world study was indeed a positive surprise,” Huei-Kai Huang, MD, PhD, physician-scientist in the department of medical research and attending physician in the department of family medicine at Hualien Tzu Chi Hospital in Taiwan, and Edward Lai, PhD, FISPE, professor in the School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine at National Cheng Kung University in Taiwan, told Healio. “It reinforces the idea that medications for bone health may also have significant metabolic benefits, which had been suggested but not further confirmed at this scale before.”
Huang, Lai and colleagues conducted a retrospective cohort study of adults in Taiwan who were prescribed 60 mg denosumab for osteoporosis treatment from 2012 to 2019 and had no history of diabetes that required medication. Data were obtained from Taiwan’s National Health Insurance Research Database. A treatment group of 34,255 adults who received their second dose of denosumab within 180 days of their initial dose were matched with a comparator group of 34,255 adults who stopped denosumab therapy after the initial dose. Researchers collected cases of new-onset diabetes in both groups. The treatment group was followed until diabetes diagnosis, denosumab discontinuation, death or the end of follow-up on Dec. 31, 2020. Adults in the comparison group were followed until diabetes diagnosis, starting or restarting any osteoporosis therapy, death or end of follow-up.
During a mean follow-up of 1.9 years, 2,016 adults in the treatment group and 3,220 adults in the comparator group developed diabetes. Adults who continued using denosumab had a lower risk for developing incident diabetes than adults who discontinued denosumab after the first dose (HR = 0.84; 95% CI, 0.78-0.9).
“Our findings suggest that physicians may consider the broader metabolic effects of denosumab when prescribing it for osteoporosis treatment,” Huang and Lai said. “This finding may help physicians choose the appropriate anti-osteoporosis medication for patients with osteoporosis while also considering lowering the incidence of diabetes.”
In subgroup analysis, adults aged 65 years and older in the treatment group had a lower risk for developing diabetes than those in the comparator group (HR = 0.8; 95% CI, 0.75-0.85). No difference between the two groups was observed for adults younger than 65 years. A reduced risk for incident diabetes was observed for men (HR = 0.85; 95% CI, 0.73-0.97) and women (HR = 0.81; 95% CI, 0.76-0.86) receiving denosumab vs. the comparator group. Adults receiving denosumab had a reduced risk for developing diabetes, regardless of whether they also had dyslipidemia, hypertension, ischemic heart disease or kidney failure.
“Further research should aim to understand more about the mechanisms by which denosumab influences glucose metabolism and diabetes risk,” Huang and Lai said. “Additionally, studies across different countries, populations and ethnicities would help to validate and expand upon our findings. Investigating the effects of denosumab, specifically in patients at high risk of or with existing metabolic conditions, could also provide valuable insights. Moreover, exploring the metabolic impacts of other types of osteoporosis medications is also needed.”
For more information:
Huei-Kai Huang, MD, PhD, can be reached at hueikaih@gmail.com.
Edward Lai, PhD, FISPE, can be reached at edward_lai@mail.ncku.edu.tw.
Perspective
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E. Michael Lewiecki, MD, FACE, FACP
Given the high global prevalence of diabetes and osteoporosis, it would be helpful to know that a medication used to treat one of these conditions might help the other. Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) that is widely used for the treatment of women and men with osteoporosis, may be such a drug.
This large retrospective cohort study examined data from the administrative health claims database of Taiwan for patients started on treatment with denosumab. There was a significant reduction in the risk for type 2 diabetes in patients who persisted with denosumab treatment compared with those who received an initial dose but did not continue. This finding supports and expands the findings of several prior studies.
There is biological plausibility for denosumab reducing the risk for diabetes. Preclinical studies have found that RANKL inhibition may reduce low grade inflammation that is associated with insulin resistance and type 2 diabetes. In addition, there is evidence that RANKL inhibition stimulates proliferation of rodent and human pancreatic beta cells, thereby increasing the availability of insulin as well as decreasing insulin resistance.
For health care professionals who often encounter patients with overwhelming concerns about rare but possible adverse effects of osteoporosis medication, it is comforting to have accumulating evidence of beneficial side effects, such as reduced risk for type 2 diabetes. Although the treatment effect with denosumab in this study is small (HR = 0.84), considering the high prevalence of diabetes, this is potentially relevant from a public health perspective.
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