Effectiveness of bisphosphonate analogues and functional electrical stimulation on attenuating post-injury osteoporosis in spinal cord injury patients- a systematic review and meta-analysis

PLoS One. 2013 Nov 22;8(11):e81124. doi: 10.1371/journal.pone.0081124. eCollection 2013.


Background: Various pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI), and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES), could effectively decrease bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI population.

Methods: Randomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention.

Results: A total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to 16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥ 5 days per week were likely to have better effectiveness than studies using FES ≤ 3 days per week.

Conclusions: Our meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly increase sublesional BMD near the site of maximal mechanical loading.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / therapeutic use*
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use*
  • Electric Stimulation / adverse effects
  • Electric Stimulation / methods*
  • Humans
  • Osteoporosis / etiology*
  • Osteoporosis / therapy*
  • Spinal Cord Injuries / complications*
  • Treatment Outcome


  • Bone Density Conservation Agents
  • Diphosphonates

Grant support

This research was supported by grants from the National Science Council (102-2314-B-002-013, 100-2314-B-002-012-MY3 and NSC 99-2320-B-002-005-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.