Romosozumab for Treatment of Osteoporosis in Advanced CKD: Series from Real-World Evidence

Background: Romosozumab, an anti-sclerostin monoclonal antibody that promotes bone formation and limits resorption, has been shown to reduce fracture risk in the general population but remains understudied in patients with advanced chronic kidney disease (CKD). We describe the real-world use of romosozumab in patients with CKD stages 3b–5D. Methods: Clinical and biochemical parameters, dual-energy X-ray absorptiometry (DXA) results, adverse events, and outcomes were retrieved and analyzed for patients with CKD and an eGFR ≤45 mL/min/1.73 m2 or those on dialysis who were prescribed romosozumab. Results: Among 34 patients, the median age was 75 years, and 29 (85%) were female. The median eGFR was 28 mL/min/1.73 m2, and 5 patients (15%) were on dialysis. The median parathyroid hormone (PTH) level was 102 pg/mL (IQR: 58.8–224.5), and the median alkaline phosphatase level was 88 IU/L (IQR: 72–139). Twenty-two patients (65%) had a history of fracture, and 10 (29%) had prior cardiovascular events. Twenty-one patients (62%) completed 12 months of romosozumab therapy, while 9 (27%) discontinued early, including 2 due to hypocalcemia. Among those who completed therapy, 14 (67%) had follow-up DXA scans, which showed no significant differences in bone mineral density (BMD) before and after treatment: 0.664 vs. 0.682 g/cm2 at the total hip (p = 0.71) and 0.946 vs. 1.058 g/cm2 at the lumbar spine (p = 0.69). The median percent change in BMD was −4.7% (−6.6 to 0.8) at the left hip, 2.7% (−4.6 to 6.6) at the right hip, 0% (−5.4 to 3.4) at the combined total hip, and 1% (−6.1 to 8.2) at the lumbar spine. One patient experienced a new fracture during treatment. Hypocalcemia occurred in 25 patients (74%), with a median calcium nadir of 7.7 mg/dL (IQR: 7.1–8.1). Cardiovascular events were reported in 2 patients (6%) during treatment and in 4 (12%) within one year after therapy. Conclusion: In contrast to the general population, where romosozumab significantly increases BMD, this small series in advanced CKD patients showed no significant improvement in BMD. Additionally, hypocalcemia was a frequent adverse event. These findings suggest a potentially blunted skeletal response to romosozumab in CKD and underscore the need for prospective studies to better assess its efficacy and safety in this population.