Osteoporosis Treatment With Anabolic Agents Is Not Associated With Increased Bone Cancer Risk

The use of anabolic agents for the treatment of osteoporosis is not associated with increased risk of development of primary bone malignancy, according to a study in the Journal of the AAOS.

“Although many risk factors for the development of primary bone tumors have been identified, there has been minimal human research into whether medications, specifically bone-forming medications, increase the likelihood of developing primary bone malignancies,” wrote Christopher L. McDonald, MD, and colleagues in their study. The authors cited an animal study which demonstrated a greater risk of osteosarcoma in rats treated with teriparatide. “Given the lack of conclusive data, this has left many providers with ongoing concerns given the theoretical risk of primary bone tumor development with the extended use of bone anabolic agents,” they wrote.

To investigate this issue, the researchers utilized the PearlDiver Mariner database to identify 44,728 patients older than 50 years with osteoporosis who were prescribed teriparatide or abaloparatide between 2010 and 2020. Risk of primary bone cancer development was compared between this group and a matched control group with osteoporosis but no history of anabolic treatment. A separate cohort of 1,241 patients with risk factors of primary bone malignancy and anabolic agent use were compared with 6,1999 matched controls to further evaluate the effect of anabolic agents.

Compared with control, anabolic-exposed patients had greater exposure to other osteoporosis medications (e.g., diphosphonates, vitamin D, denosumab) and were more likely to have exposure to hereditary multiple osteochondromas (HMO) and alkylating agents. Before matching and exclusion criteria, a greater number of patients who were not prescribed anabolic agents were found to have cancer, including chronic lymphocytic leukemia (P=.0015) and primary bone malignancy (P=.0016).

After exclusion and matching criteria were applied, the chi square analysis based on age group and sex on the matched sample did not find a statistically significant difference in the rate of bone cancer between patients exposed and unexposed to anabolic agents. In total, 11 patients (0.02%) in the anabolic treatment group and 116 patients (0.05%) in the control group developed a primary bone malignancy during the 10-year study period. The incidence rate per 100,00 person-years was 3.61 for anabolic-exposed patients and 6.46 for controls. The risk ration for development of a bone neoplasm in patients exposed to anabolic agents was 0.47 (95% confidence interval, 0.30-1.04; P=.052).

“To the best of our knowledge, this is the first study to find that patients taking bone anabolic agents have a statistically significantly lower risk of developing primary bone neoplasms,” the authors wrote. “However, at this point, it cannot be concluded that teriparatide and abaloparatide have protective effects, … and these findings should speak more toward a lack of risk regarding primary bone malignancies.”

The authors acknowledged several limitations of their study, including its retrospective and database design. Additionally, the database did not record the dose of prior radiation exposure, which is a malignancy risk factor, and there was a difference in the average follow-up between patients in the treatment and control groups. “Having longer follow-ups to 10 years and longer would also be able to identify a greater number of cases of tumor development, further strengthening our results,” they noted.