Romosozumab in postmenopausal women with smoldering multiple myeloma: a prospective 12-mo study.

Bone damage occurs early in the progression of plasma cell disorders. Romosozumab (ROMO), a sclerostin inhibitor with both anabolic and antiresorptive effects, may provide therapeutic benefit for this fracture-prone population. We conducted a 12-mo prospective observational study on postmenopausal women with osteoporosis and multiple myeloma (MM) treated with monthly ROMO. BMD was assessed at baseline, 6, and 12 mo with DXA and HR-pQCT. Additionally, bone turnover markers (BTMs) and several MM markers were also monitored. Eight female patients with MM without evidence of CRAB completed 12 mo of ROMO. A significant BMD increase was observed at the LS (+5.8%, p = .048), FN (+4.2%, p = .020), and TH (+3.3%, p = .002). Procollagen I intact N-terminal peptide rose sharply at month 3 (+117.8%) and returned to baseline by month 12 (p = .006). C-terminal telopeptide of type I collagen decreased progressively, showing a trend toward significance (-53.6%, p = .060). Alkaline phosphatase and bone alkaline phosphatase significantly declined by month 12 (p = .020 and p = .022). No significant changes occurred in immunoglobulins, M-protein, or light chains. β2-microglobulin decreased at month 12 (from 2.35 to 2.1 mg/L, p = .042), but the overall trend was not significant (p = .092). Failure load increased at month 6 (p = .033), while the other HR-pQCT parameters remained stable throughout the study. In this exploratory study of postmenopausal women with MM and osteoporosis, ROMO significantly improved BMD and modulated BTMs, without any evidence of disease progression over the 12-mo period. These findings support ROMO as a potential bone-targeted therapy in patients with osteoporosis and MM.