Endocrine Abstracts

JOINT94

Introduction: Two anabolic agents, namely teriparatide (parathyroid hormone analogue) and abaloparatide (parathyroid hormone-related peptide analogue), are approved by the Food and Drug Administration for osteoporosis. in vitro studies however, noted a heightened risk for osteosarcoma among rodents, for which a black box warning was given, as well as a limit of exposure; only recently has the two-year limit for Teriparatide been removed, however, an 18-month limit persists with abaloparatide. It should be noted, however, that the dosages used in vitro were supraphysiologic compared to those used in humans. Current recommendations are to only continue teriparatide beyond two years after shared decision making.

Objectives: Teriparatide has been on the market since 2002, and abaloparatide since 2017; as a result, the purpose of this retrospective cohort study is to evaluate the risk for osteosarcoma in patients with osteoporosis who are treated with an anabolic agent (teriparatide or abaloparatide). This study will address the validity of the black box warning of osteosarcoma in anabolic agents.

Methods: Anonymized data was collated through TriNetX Collaborative Network, encompassing 143 healthcare organizations globally. Cohorts were defined based on osteoporosis and the presence of an anabolic agent (teriparatide or abaloparatide) (n = 47, 489) and those with osteoporosis without an anabolic agent (n = 2, 686, 945). Cohorts were balanced with propensity scoring, delivering a balance of n = 46, 909. There was no age limit (upper or lower) for study inclusion, and all genders were included. The primary outcome of interest was the relative risk for the development of osteosarcoma (malignant neoplasm of bone). Timeframe was set as from at least one day following drug exposure to the present. Cohorts were matched for age at index and current age, gender, race, history of malignancy, and Paget’s disease of bone.

Results: After matching, the mean age at index was 68.3 +/- 11.6 years, with 84.5% of the cohort being female, and 70.4% white. When assessing the risk for osteosarcoma, there was no significant difference between the group treated with anabolic agents and those without (Relative Risk 0.714, 95% CI: 0.476-1.072, P = 0.1024).

Conclusion: The results from this study suggest there is no heightened risk for osteosarcoma with anabolic agents teriparatide or abaloparatide. Perhaps the black box warning is unnecessary and should be dropped upon further advisory committees.