The Role of Sclerostin in Spinal Cord Injury: A Scoping Review

Objective(s): To map the existing literature surrounding the role of the protein sclerostin regarding spinal cord injury (SCI) and bone health outcomes. Research question(s): 1) What is the evidence on the usefulness of the protein sclerostin as a biomarker of bone health in patients with spinal cord injury? and 2) What is the evidence surrounding the protein sclerostin as a therapeutic target in patients with spinal cord injury to ameliorate disease induced bone loss?

Data Sources: Four databases were consulted for the detailed search of the scientific literature, EMBASE, SCOPUS, MEDLINE, and PUBMED. References of eligible articles were screened for additional relevant papers.

Study Selection: Studies that reported bone health related outcome measures; sclerostin values, bone mineral density (BMD), biomolecular or structural changes in bone in individuals with SCI or animal models were included Fifteen studies including case-control, RCT, cross sectional and prospective studies met inclusion criteria.

Data Extraction: Data was extracted independently by the lead author as per an a priori tool and included author and date, country, number of participants, population (human/animal), study design, aim of the study, sclerostin outcome measures, and associations between sclerostin levels/therapy and health outcomes.

Data Synthesis: Human cross-sectional studies reported positive associations between circulating sclerostin levels and BMD in chronic SCI. No association was found to exist between sclerostin levels and BMD in acute SCI. Results suggest that sclerostin levels are related to an increase in age in people with SCI and suggest a potential use for sclerostin as a marker of bone mineral density in chronic SCI. Animal studies reported positive effects of antibody therapy ameliorating SCI induced decrements in bone health outcome measures both locally and systemically.

Conclusions: Due to the heterogeneity of the results obtained, we cannot robustly demonstrate a relationship between sclerostin levels and proportional declines in bone health in all SCI contexts. There does appear to be a positive trend in the specific populations investigated, mainly an older male population. in the chronic stage of SCI. It is encouraged that further research be expanded to more diverse populations, such as young adults and female populations. Pharmacological inhibition of sclerostin using antibody therapy, administered shortly after an injury, may offer a potential approach to prevent bone loss following SCI. Future research should thoroughly explore the use of this therapy in the human SCI population.

Author(s) Disclosures: Authors declare no conflicts of interest.