Beyond antifracture efficacy: Osteoanabolic versus antiresorptive therapy for chronic pain after osteoporotic vertebral fractures. A systematic review and meta-analysis.

Osteoporotic vertebral fractures (OVFs) associated pain can last long, reducing health-related quality of life. Concurrent risk of new fractures warrants osteoporosis therapies, i.e., antiresorptive [bisphosphonates and the anti-RANKL monoclonal antibody (mAb) denosumab] or osteoanabolic [teriparatide, abaloparatide, and the anti-sclerostin mAb romosozumab] agents, the latter demonstrating greater antifracture efficacy, but unclear effect on post-fracture pain. The present systematic review and meta-analysis explore whether osteoanabolics exert better pain control compared to antiresorptives in the medium- (3-6 months) to long-term (12-24 months) treatment of OVFs patients. After search in PubMed, Scopus, and Web of Science, fifteen studies (4029 patients) were included: six randomized controlled trials (RCTs, 2345 patients) and nine non-randomized studies of interventions (NRSIs, 1684 patients), whose risk of bias was assessed by using RoB-2 and ROBINS-I V2 tools, respectively. Data on pain measurement by using the Visual Analogue Scale, the Numeric Rating Scale, or dedicated domains of health-related quality-of-life instruments (QUALEFFO-41) were extracted and, when possible, meta-analyzed. Separate meta-analyses of RCTs or NRSIs show no statistically significant difference in pain control between osteoanabolic and antiresorptive drugs. Combined exploratory meta-analysis of RCTs and NRSIs favored osteoanabolic therapy, but in association with very high heterogeneity and no robustness in sensitivity analyses, thus just regarded as hypothesis-generating. Future studies should clarify the pathophysiological mechanisms of persistent pain following OVFs and their correlation with different clinical phenotypes predictive of differential responses to antifracture therapies. The applied protocol for this systematic review/meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD420261281929).