#804 Evaluation of sequential romosozumab-denosumab therapy for osteoporosis in maintenance hemodialysis patients

Abstract Background and Aims The risk of fractures in dialysis patients is approximately 5–6 times higher than in the general population. Osteoporosis significantly impacts the activities of daily living (ADL) and prognosis of dialysis patients. Despite the evident need for treatment, managing osteoporosis in these patients is challenging due to limited medication options, cautious administration requirements, and contraindications. As a result, treatment tends to be conservative and lacks well-established protocols. This study evaluated the efficacy of sequential therapy combining romosozumab, a humanized monoclonal antibody targeting sclerostin, and denosumab, a human monoclonal antibody targeting RANKL. Romosozumab was administered in the first year to promote bone formation, followed by denosumab in the second year to inhibit bone resorption. We measured changes in bone mineral density (BMD) and bone metabolic markers to evaluate the effects of this treatment approach. Method From April 2019 to December 2024, 23 maintenance hemodialysis patients from our institution were enrolled in this study. The cohort included 3 males and 20 females, with a median age of 74.6 years (range: 47–88) and a median dialysis history of 11.8 years (range: 2–29). The inclusion criteria required no history of cardiovascular complications within the past year and no difficulty in calcium (Ca) management. Patients received romosozumab, administered monthly for the first year, followed by denosumab, administered every six months during the second year. BMD of the lumbar spine and femoral neck was measured every three months using dual-energy X-ray absorptiometry (DXA). Serum whole-parathyroid hormone (whole-PTH), corrected calcium (Ca), and phosphorus (P) levels, and bone metabolic markers such as tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase (BAP), and type I procollagen N-terminal propeptide (P1NP)—were measured monthly. Pre-treatment values, averages at the end of the first and second years, and values at 24 months were compared to evaluate the outcomes of the treatment. Results A comparison between pre-treatment and 24-month measurements revealed significant improvements in BMD. Lumbar spine BMD increased from 68.4 (44–96) at baseline to 80.7 (49–110) at 24 months (P < 0.001). Femoral neck BMD also improved significantly, increasing from 54.6 (37–68) at baseline to 56.1 (35–74) at 24 months (P = 0.012) (Fig. 1). During the one-year romosozumab phase, lumbar spine BMD increased from 74.4 (63.4–92.5) to 86.8 (71.1–98.1) during the denosumab phase (P < 0.001). Similarly, femoral neck BMD improved from 57.3 (49.7–63.7) to 61.0 (52.1–64.9) (P < 0.001) (Fig. 2). Bone metabolic markers also showed significant reductions in the second year. Whole-PTH decreased from 85.0 (64.0–136.1) pg/mL in the first year to 65.6 (41.3–80.2) pg/ml in the second year (P < 0.001). TRACP-5b decreased from 318.8 (211.8–440.3) mU/dl to 152.2 (117.5–253.5) mU/dl (P < 0.001). BAP decreased from 15.8 (11.9–18.7) μg/L to 9.32 (7.8–11.4) μg/L (P < 0.001), while P1NP decreased from 302.9 (217.9–470.5) ng/ml to 145.1 (91.9–253.9) ng/ml (P < 0.001) (Fig. 2). The continued improvement in bone resorption markers observed during the denosumab phase suggests that the bone-forming effects of romosozumab, followed by the bone resorption inhibitory effects of denosumab, may have contributed to sustained improvements in bone mineral density. Conclusion Sequential therapy with romosozumab and denosumab demonstrates potential as a promising treatment strategy for osteoporosis in maintenance hemodialysis patients. By combining romosozumab's bone formation-stimulating effects and denosumab's bone resorption-inhibiting effects, this approach may significantly improve bone mineral density and stabilize bone metabolism in this high-risk population. While further studies are required to confirm its long-term efficacy and safety, this therapy offers a promising option for managing osteoporosis in hemodialysis patients.