Beyond antifracture efficacy: Osteoanabolic versus antiresorptive therapy for chronic pain after osteoporotic vertebral fractures. A systematic review and meta-analysis.
This systematic review found no significant difference in pain control between osteoanabolic and antiresorptive therapies for osteoporotic vertebral fractures, highlighting the need for further research.
Where it sits
this study against the rest of the abaloparatide (tymlos) corpusSummary and findings
This systematic review and meta-analysis assessed pain control in patients with osteoporotic vertebral fractures (OVFs) treated with osteoanabolic versus antiresorptive therapies. A total of 4029 patients were included across fifteen studies, with six randomized controlled trials (RCTs) involving 2345 patients. The findings indicated no statistically significant difference in pain control between the two treatment categories.
Abstract
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).
Background
This paper addresses the clinical question of pain management in patients with osteoporotic vertebral fractures (OVFs), a condition known to significantly impact health-related quality of life. Previous studies have indicated that while osteoanabolic agents demonstrate greater antifracture efficacy, their effect on post-fracture pain remains unclear. This systematic review and meta-analysis aims to compare the effectiveness of osteoanabolic versus antiresorptive therapies in controlling pain associated with OVFs over medium to long-term treatment periods.
Methods
The study design involved a systematic review and meta-analysis of fifteen studies, including six randomized controlled trials (RCTs) with 2345 patients and nine non-randomized studies of interventions (NRSIs) with 1684 patients. Pain measurement was conducted using the Visual Analogue Scale, Numeric Rating Scale, or dedicated domains of health-related quality-of-life instruments (QUALEFFO-41). The duration of treatment was categorized into medium-term (3-6 months) and long-term (12-24 months).
Results
The primary endpoint indicated no statistically significant difference in pain control between osteoanabolic and antiresorptive therapies. The exploratory meta-analysis suggested a potential favoring of osteoanabolic therapy; however, this was accompanied by very high heterogeneity and a lack of robustness in sensitivity analyses.
Interpretation
The findings suggest that while osteoanabolic therapies may show some potential for better pain control, the statistical significance is not robust, and the clinical relevance remains uncertain. The high heterogeneity in the results indicates that further research is necessary to explore the underlying mechanisms of pain in OVFs and to identify which patient phenotypes may respond differently to these therapies. This study adds to the existing literature but does not provide conclusive evidence for clinical practice.
Key findings
- 4029 patients included across fifteen studies.
- 2345 patients from six randomized controlled trials (RCTs).
- 1684 patients from nine non-randomized studies of interventions (NRSIs).
- No statistically significant difference in pain control between osteoanabolic and antiresorptive drugs.
- Combined exploratory meta-analysis favored osteoanabolic therapy but showed very high heterogeneity.
Limitations
- High heterogeneity in meta-analysis results.
- Lack of robustness in sensitivity analyses.
- Not all studies were randomized controlled trials.
- Future studies needed to clarify pain mechanisms.