Background/Purpose: Bone damage is a key feature of multiple myeloma (MM). Romosozumab (ROMO), a sclerostin inhibitor, has dual anabolic and antiresorptive properties and may offer benefit in this group with high fracture risk.

Methods: We did a 12-month prospective observational study in patients with multiple myeloma (MM) and osteoporosis treated with ROMO. Inclusion criteria were: (1) diagnosis of MM according to the International Myeloma Working Group (IMWG) definition, (2) absence of CRAB disease, (3) treatment with ROMO deemed necessary by the treating physician. The primary outcome was bone mineral density (BMD) change at 12 months, other outcomes were bone turnover markers (BTMs) change, high-resolution peripheral computed tomography (HR-pQCT) parameters and MM related parameters (M-protein, immunoglobulins free light chains, β2-microglobulin). We used mixed model for repeated measures analyses with random intercepts by participant with time as independent variables with an unstructured correlation matrix.

Results: Eight female patients with MM (mean age 67.4±9.9 years) completed 12 months of ROMO (table 1). A significant BMD increase was observed at all evaluated sites over the study period (figure 1). Lumbar spine BMD increased by 5.8% (7.7) at 12 months (p=0.048). Femoral neck increased by 4.2% (3.9) (p=0.020) and total hip by 3.3% (2.4) (p=0.002). Bone-alkaline phosphatase (B-ALP) showed a significant decrease by month 12 (13.5 (9.3-17) to 9 (6.12) ng/mL, p=0.022). P1NP rose sharply by month 3, from 60 (49.5-70.3) to 98 (77-115.5) ng/mL (mean change of 117.8%), but then declined, approaching baseline by month 12 (p=0.006). Conversely, CTX showed a tendency for reduction at all time points (p=0.060), with a maximal decrease at the end of the 12 months (-53.6%, figure 2). No significant changes occurred in immunoglobulins, M-protein, or light chains. β2-microglobulin showed a downward trend (from 2.35 to 2.1mg/L at month 12, p=0.042), though overall changes were not significant (p=0.092). HR-pQCT parameters remained stable throughout the study, revealing no changes in volumetric BMD, microarchitecure or biomechanical properties of the bone assessed with this method.

Conclusion: In this exploratory study of patients with MM and osteoporosis, ROMO significantly improved BMD and modulated BTMs, without any evidence of disease progression over the 12-month period. These findings support ROMO as a potential bone-targeted therapy in patients with osteoporosis and plasma cell disorders.

Baseline characteristics of the study population

Percentage Change from Baseline in Bone Mineral Density at the lumbar spine (A), total hip (B) and femoral neck (C)

Percentage Change from Baseline in P1NP levels (A) and CTX levels (B)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/romosozumab-in-multiple-myeloma-patients-at-high-risk-of-fracture/