Romosozumab, a monoclonal anti-sclerostin antibody that has the dual effect of increasing bone formation and decreasing
bone resorption, reduces fracture risk within 12 months. In a post hoc, exploratory analysis, we evaluated the effects of
romosozumab after 12 months of
denosumab in postmenopausal women with low bone mass who had not received previous
osteoporosis therapy. This phase 2 trial (NCT00896532) enrolled postmenopausal women with a lumbar spine, total hip, or femoral neck T-score ≤ -2.0 and ≥ -3.5. Individuals were randomized to placebo or various
romosozumab dosing regimens from baseline to month 24, were re-randomized to 12 months of
denosumab or placebo (months 24-36), and then all received
romosozumab 210 mg monthly for 12 months (months 36-48). Results for the overall population have been previously published. Here, we present results for changes in bone mineral density (BMD) and levels of
procollagen type I N-terminal propeptide (P1NP) and β-isomer of the
C-terminal telopeptide of type I collagen (β-CTX) from a subset of women who were randomized to placebo for 24 months, were re-randomized to receive
denosumab (n = 16) or placebo (n = 12) for 12 months, and then received
romosozumab for 12 months. In women who were randomized to placebo followed by
denosumab,
romosozumab treatment for 12 months maintained BMD gained during
denosumab treatment at the total hip (mean change from end of
denosumab treatment of 0.9%) and further increased BMD gains at the lumbar spine (mean change from end of
denosumab treatment of 5.3%). Upon transition to
romosozumab (months 36-48), P1NP and β-CTX levels gradually returned to baseline from their reduced values during
denosumab administration. Transitioning to
romosozumab after 12 months of
denosumab appears to improve lumbar spine BMD and maintain total hip BMD while possibly preventing the rapid increase in levels of bone turnover markers above baseline expected upon
denosumab discontinuation. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and
Mineral Research.