Odanacatib safe and efficacious alternative for treatment of osteoporosis among postmenopausal women: Study

Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and bone tissue deterioration, leading to bone fragility and a susceptibility to fractures, which presents a threat to the quality of life in postmenopausal women. Even though several treatments exist, there is still a continuing need for effective and safe therapies. Odanacatib (ODN) is a novel class of pharmacotherapy targeted against CatK, an enzyme pivotal in bone resorption. Because of its promise, a meta-analysis was undertaken regarding the efficacy and safety of ODN for the treatment of PMOP, by assessing its impact on BMD and biomarkers of bone turnover together with its related adverse events (AEs).

The PRISMA checklist was followed for this review, and the literature search was carried out up until 29th December 2023 through databases like PubMed, EMBASE, Cochrane Library, and Web of Science. Afterwards, four RCTs that match the stringent inclusion criteria were combined to ensure reliable and high-quality results. Bias risk in the trial was carefully assessed using the tool prepared by the Cochrane Collaboration. Included within the major outcomes of interest were changes in BMD at different sites [lumbar spine, femoral neck, total hip, trochanter and forearm] and levels of bone turnover biomarkers, P1NP, uNTx/Cr, s-CTx, BSAP. Safety assessment was done by analyzing the number of subjects who developed total, serious, other and skin-related adverse events.

Results

• ODN significantly increased BMD at various sites, including the lumbar spine, femoral neck, total hip, and trochanter versus placebo, with benefits becoming more pronounced with continued treatment.

• At 12 months, ODN significantly increased lumbar spine BMD with a WMD of 3.02 (95% CI: 1.73, 4.31, P < 0.0001). At 24 months, the increase in lumbar spine BMD was highly significant with a weighted mean difference (WMD) of 5.01 (95% CI: 3.68, 6.34, P < 0.001).

• ODN resulted in significant increases in femoral neck and total hip BMD at both 12 and 24 months. More specifically, at 12 months, FN BMD demonstrated a WMD of 1.95 (95% CI: 1.36, 2.54, P = 0.056), and at 24 months, TH BMD demonstrated a WMD of 3.76 (95% CI: 2.89, 4.63, P = 0.006).

• ODN was associated with a significant reduction of biomarkers related to bone turnover: P1NP, uNTx/Cr, s-CTx, and BSAP. In this respect, the level of P1NP significantly was lowered with the WMD of -20.56 (95% CI: -34.65, -6.47, P = 0.003) at 12 months as an indicator of less fracture risk.

• Safety and Adverse Events: No significant differences were observed in the incidence of total adverse events, serious adverse events, or skin-related adverse events between the ODN and placebo groups, indicating a similar safety profile.

The study concluded that odanacatib has demonstrated exceptional effectiveness in increasing bone mineral density and decreasing bone turnover in postmenopausal osteoporotic women. Its safety profile also appears to be rather valid, as there is no significant difference in the incidence of adverse events compared with placebo administration. Further investigations should be conducted with respect to the unexplained relationship between ODN and cardiovascular adverse events. Overall, ODN seems to be a new hope for treating postmenopausal osteoporosis and improving quality of life in this population.

Reference:

Li, J., Qiu, Q., Jiang, S., Sun, J., Pavel, V., & Li, Y. (2024). Efficacy and safety of odanacatib in the treatment of postmenopausal women with osteoporosis: a meta-analysis. Journal of Orthopaedic Surgery and Research, 19(1). https://doi.org/10.1186/s13018-024-05008-z