Real World Experience Demonstrating Limited Efficacy of Denosumab in Osteonecrosis of the Hip

Background: Osteonecrosis of the femoral head (ONFH) is a progressive condition that often ends in collapse of the head and necessitates Total Hip Arthroplasty (THA). Drugs intended to preserve the native hip have given inconsistent and variable results. Denosumab is a monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL); it blocks osteoclast-mediated bone resorption and has shown promise in experimental work and early clinical reports in the treatment of ONFH. The aim of our study is to evaluate whether denosumab delays radiological progression and reduces the need for THA in patients with ONFH. Methods: We retrospectively reviewed patients with Ficat-Arlet Stage I-III ONFH treated with denosumab at a tertiary care centre between January 2019 and December 2022. Those with Stage IV disease, hip arthritis, contraindications to denosumab, or insufficient follow-up were excluded, leaving 17 patients (31 hips) followed for at least three years. Denosumab was given as 120 mg monthly for three months and then 60 mg every six months for three years. Pain and function were tracked with the Visual Analogue Scale (VAS) and Harris Hip Score (HHS), and radiological progression with serial radiographs and MRI. Progression was defined as advancement of the Ficat-Arlet stage and collapse as progression to Stage III or beyond; conversion to THA was treated as treatment failure. Results: The mean age was 41.6 years (range, 20 - 58). At presentation, 25 hips (80.6%) were Stage II, five (16.1%) were Stage III, and one (3.2%) was Stage I. The mean VAS decreased from 6.81 at baseline to 5.32 at one year, whereas the mean HHS barely changed, rising from 61.16 to 62.77 over the same interval. Radiological progression was seen in the single Stage I hip (100%), in 10 of 25 Stage II hips (40%), and in three of five Stage III hips (60%). Collapse occurred in 11 hips overall, and nine (29%) hips required THA (clinical failure rate). Conclusion: Denosumab did little to prevent radiological progression, collapse, or conversion to THA in this cohort. Pain eased modestly, but functional gains were minimal, and a sizeable proportion of hips progressed despite treatment. On this evidence, denosumab is unlikely to work as a standalone joint-preserving therapy for ONFH, and prospective controlled studies are needed to clarify what role, if any, it has in managing the condition.