The role of sclerostin in spinal cord injury: A scoping review

CONTEXT: Sclerostin, an antagonist of the Wnt/β-catenin signaling pathway, serves as a negative regulator of bone formation by inhibiting osteoblast activity. Following spinal cord injury (SCI), disruption of mechanical loading and systemic physiological changes lead to dysregulated sclerostin expression. Despite its known importance, the evidence regarding sclerostin's utility as a predictive biomarker and its potential as a therapeutic target remains unmapped. OBJECTIVE(S): This scoping review synthesizes the existing evidence on the role of sclerostin in SCI and its implications for bone health outcomes, providing a systematic overview of its associations and addressing an aspect of the existing knowledge gap in our understanding of the mechanisms underlying post-SCI bone loss. METHODS: A literature search was conducted in EMBASE, SCOPUS, MEDLINE, and PUBMED. Data were independently extracted, capturing study details, sclerostin measures, and associations with bone health. RESULTS: Cross-sectional studies showed a positive association between sclerostin and bone mineral density in chronic SCI but not in acute SCI. Sclerostin levels also appeared to increase with age. Animal studies indicated that antibody therapy might reduce SCI-related bone loss. CONCLUSIONS: The results were heterogeneous, preventing strong conclusions. A positive trend was noted in chronic SCI, but further research is needed, particularly in postmenopausal females and pediatric populations. Pharmacological inhibition of sclerostin shows promise but requires more investigation in human SCI.