Evidence-based prevention and treatment of osteoporosis after spinal cord injury: a systematic review
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PURPOSE: Spinal cord injury (SCI) results in accelerated bone mineral density (BMD) loss and disorganization of trabecular bone architecture. The mechanisms underlying post-SCI osteoporosis are complex and different from other types of osteoporosis. Findings of studies investigating efficacy of pharmacological or rehabilitative interventions in SCI-related osteoporosis are controversial. The aim of this study was to review the literature pertaining to prevention and evidence-based treatments of SCI-related osteoporosis. METHODS: In this systematic review, MEDLINE, EMBASE, PubMed, and the Cochrane Library were used to identify papers from 1946 to December 31, 2015. The search strategy involved the following keywords: spinal cord injury, osteoporosis, and bone loss. RESULTS: Finally, 56 studies were included according to the inclusion criteria. Only 16 randomized controlled trials (involving 368 patients) were found. We found following evidences for effectiveness of bisphosphonates in prevention of BMD loss in acute SCI: very low-quality evidence for clodronate and etidronate, low-quality evidence for alendronate, and moderate-quality evidence for zoledronic acid. Low-quality evidence showed no effectiveness for tiludronate. In chronic SCI cases, we found low-quality evidence for effectiveness of vitamin D3 analogs combined with 1-alpha vitamin D2. However, low-quality inconsistent evidence exists for alendronate. For non-pharmacologic interventions, very low-quality evidence exists for effectiveness of standing with or without treadmill walking in acute SCI. Other low-quality evidences indicated that electrical stimulation, tilt-table standing, and ultrasound provide no significant effects. Very low-quality evidence did not show any benefit for low-intensity (3 days per week) cycling with functional electrical stimulator in chronic SCI. CONCLUSIONS: No recommendations can be made from this review, regarding overall low quality of evidence as a result of high risk of bias, low sample size in most of the studies, and notable heterogeneity in type of intervention, outcome measurement, and duration of treatment. Therefore, future high-quality RCT studies with higher sample sizes and more homogeneity are strongly recommended to provide high-quality evidence and make applicable recommendations for prevention and treatment of SCI-related bone loss.