Refracture following vertebral fragility fracture when bone fragility is not recognized: summarizing findings from comparator arms of randomized clinical trials

Purpose: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. Results: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9–16] and 6 (95% CI 5–8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. Conclusion: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures.