Risk factors and clinical correlations of heterotopic ossification following spinal cord injury: a systematic review and meta-analysis

A systematic review and meta-analysis. To systematically evaluate the clinical correlates and relative risks of heterotopic ossification (HO) following spinal cord injury (SCI), and to provide an evidence-based framework for clinical HO prevention based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Electronic literature searches were conducted across four databases: PubMed, Web of Science, Embase, and the Cochrane Library. Statistical analyses were performed using Review Manager 5.4 and R 4.5.2. Risk of bias and evidence quality were systematically assessed utilizing the Quality In Prognosis Studies (QUIPS) tool and the GRADE framework. A total of 11 studies (n = 2,647) were included in the meta-analysis. The results demonstrated that complete SCI, male sex, pressure ulcers, spasticity, and DVT were significantly associated with the occurrence of HO post-SCI (P < 0.05). Initial analysis indicated a positive correlation for UTI (P = 0.02); however, sensitivity analysis revealed insufficient robustness. Cervical versus thoracic injury level, smoking status, and pneumonia exhibited no significant associations with HO. GRADE Assessment: Evidence for male sex, spasticity, pressure ulcers, and DVT was rated as moderate-quality. Complete SCI was downgraded to low-quality evidence due to publication bias (trim-and-fill adjusted OR = 5.45, 95% CI 3.78–7.84, P < 0.0001), and evidence for UTI was rated as very low-quality. Male sex, spasticity, pressure ulcers, and DVT are reliable predictors for the development of HO following SCI. Furthermore, patients with complete SCI should be monitored as a high-risk cohort. These findings suggest that the aforementioned factors can serve as critical indicators for early screening and intervention of HO. Future high-quality prospective studies are warranted to further validate these potential associations.