Treatment with zoledronic acid subsequent to odanacatib prevents bone loss in postmenopausal women with osteoporosis.

Abstract

The development of odanacatib (ODN), a cathepsin K inhibitor, for treatment of osteoporosis was discontinued due to an increased risk of cardiovascular events. As the treatment is considered reversible, participants from the LOFT trial in Aarhus, Denmark, were offered treatment with zoledronic acid (ZOL). Sixty-seven postmenopausal women were treated with ZOL 5mg and followed for 12months. Of these, 39 had received ODN for 7years and 28 had received placebo for 5years and ODN for 2years. Bone turnover markers (BTM) were measured 3, 6, and 12months after ZOL, and DXA of spine and hip were performed at time of ZOL treatment and after 12months. Within the entire study population, BMD at the lumbar spine increased by 2.8 ± 0.9% (mean ± SEM) (p < 0.01) from baseline to month 12. There was no significant change in BMD at the total hip (p = 0.17) or femoral neck (p = 0.39). There was no difference in the changes in BMD from baseline to 12months between the two groups at any site (p ≥ 0.20 for all). CTX increased by 107 ± 9% (p < 0.001), PINP by 102 ± 16% (p < 0.001), osteocalcin by 32 ± 6% (p = 0.001) and BSAP by 79 ± 37% (p = 0.001) between 3 and 12months after ZOL. At month 12, BTM were still within the premenopausal reference range. S-25-hydroxyvitamin D increased (p = 0.059), while PTH (p = 0.007) and eGFR (p = 0.014) decreased during the year following ZOL administration. Treatment with ZOL 5mg maintained BTMs in the premenopausal range and prevented bone loss in women previously treated with ODN.