Denosumab vs placebo efficacy in bone mineral density, bone turnover markers, and function in osteopenic patients with lumbar degenerative diseases after lumbar fusion surgery: a randomized controlled trial

Abstract Objective: Denosumab has been shown to be effective in increasing bone mineral density (BMD) in postmenopausal women with osteoporosis. However, the effect of denosumab on BMD, bone turnover markers (BTMs), and quality of life in osteopenic patients after spinal fusion remains unknown. Methods: We performed a randomized, double blinded, placebo-controlled clinical trial in osteopenic patients with lumbar degenerative diseases. All participants underwent lumbar fusion, received calcium (1200 mg/day) and vitamin D (800 IU/day) supplementation, and were randomized to receive subcutaneous injection of 60 mg denosumab or placebo every 6 months post-surgery. Patients were followed for up to 12 months post-operation. Results: We found that denosumab significantly improved percentage BMD of lumbar spine by 5.35% vs -0.45%, total hip by 3.68% vs -0.72%, and femoral neck by 3.41% vs -0.69% compared with placebo, at 12-month timepoint (p<0.05). Denosumab significantly decreased percentage change of amino-terminal propeptide of type 1 procollagen P1NP and β-C-terminal telopeptide of type 1 collagen CTX compared with placebo in osteopenic patients after lumbar fusion at the 12-month follow-up (p<0.05). Denosumab improved the Visual Analogue Scale (VAS) back scores, though no significant difference in VAS leg score, the EuroQol Five-Dimension (EQ-5D) questionnaire, the Quality of Life Questionnaire of the European Foundation for Osteoporosis-31 (QUALEFFO-31), and the Roland-Morris Disability Functioning Questionnaire (RMDQ) compared with the placebo group at the 12-month follow-up. Lastly, no significant difference was observed for the rate of new fractures, re-operation, complications, and adverse events between denosumab and placebo groups at the 12-month follow-up. Conclusion: Ultimately, our data demonstrate that denosumab is effective in increasing BMD of lumbar spine, total hip and femoral neck, suppression of BTMs and maintaining functional status in osteopenic patients after lumbar fusion surgery.