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Effectiveness of bisphosphonate analogues and functional electrical stimulation on attenuating post-injury osteoporosis in spinal cord injury patients – a systematic review and meta-analysis |
Chang KV, Hung CY, Chen WS, Lai MS, Chien KL, Han DS |
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CRD summary The authors concluded that the early administration of bisphosphonates after spinal cord injury effectively reduced sub-lesional bone loss. Functional electrical stimulation for chronic injury could significantly increase sub-lesional bone mineral density. They relied on before-and-after data, which limits the comparison of intervention effectiveness. Small samples and variable studies also limit the reliability of the authors' conclusions. Authors' objectives To investigate whether bisphosphonate analogues and functional electrical stimulation (FES) could effectively slow the loss of bone mineral density (BMD), restore lost BMD or both, in people with spinal cord injury. Searching PubMed, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov were searched up to January 2013. Bibliographies of included articles and the references of related systematic reviews were searched. Search terms were reported. No language restrictions were applied. Study selection Randomised controlled trials (RCTs), quasi-experimental studies, and prospective follow-up studies were eligible for inclusion if they focused on bisphosphonate analogues and FES to treat osteoporosis after a spinal cord injury. Childrenand those with specific causes for spinal cord injury (such as infection, neoplasm, inflammatory diseases, and vasculopathy) were excluded. FES had to consist of electrical currents to activate nerves innervating paralytic extremities to perform a functional task, such as cycling, ambulation, or resistance training. The primary outcome was the percentage change in bone mineral density from baseline measured by dual-energy X-ray absorptiometry or computed tomography. In the included studies, the mean age of participants ranged from 24 to 42 years, and most of them were men. They either had acute or chronic spinal cord injury, at a level that varied from C2 to T12. Bisphosphonate regimens included oral alendronate, oral etidronate, intravenous zoledronic acid, and intravenous pamidronate. The control groups received usual care, normal saline injections or placebo tablets. FES was FES cycling ergometry or FES plus resistance training. The dosage of bisphosphonate, frequency and the duration of both treatments, and the site of bone mineral density measurement varied between studies. The authors did not state how many reviewers selected the studies for inclusion. Assessment of study quality The quality of the trials was assessed using the Jadad scale, which ranged from 0 to 5 (scores below 3 were considered low quality). Prospective cohort and longitudinal studies were evaluated using the Newcastle-Ottawa scale for quality of selection, comparability, exposure, and outcome. The maximum score was 9 (scores below 4 were considered low quality). Two authors independently assessed study quality; any discrepancies were resolved by discussion and consensus. Data extraction Two authors independently extracted the data, at three, six, 12, and 18 months after intervention, to calculate estimates of percentage changes in bone mineral density with 95% confidence intervals. Methods of synthesis Pooled estimates of percentage change in bone mineral density, with 95% confidence intervals, were calculated using the random-effects model. Heterogeneity was measured using Ι² and Cochran’s Q; Ι² over 50% was considered evidence of heterogeneity. Subgroup analyses were conducted by the post-injury duration, route of bisphosphonate administration, and frequency of FES training. Results of the review Nineteen studies (focusing on bisphosphonate: seven RCTs and one quasi-experimental study; focusing on FES: nine longitudinal studies and two quasi-experimental studies) were included in the analysis. There was a total of 364 patients and 14 healthy individuals (range six to 55 participants). In studies of bisphosphonate, four of the seven trials scored 3 or more (indicating higher quality); the quasi-experimental study was low quality. None of the studies of FES were considered low quality; the two quasi-experimental studies were rated high quality. There was a trend towards less bone loss up to 18 months from the start, in patients with acute spinal cord injury who received bisphosphonate and FES; these results were compared separately from control. With FES training, people with chronic spinal cord injury had increases in BMD from the start of 5.96% (95% CI, 2.08 to 9.84) at three months, 7.21% (95% CI, 1.79 to 12.62) at six months, and 9.56% (95% CI, 2.86 to 16.26) at 12 months after treatment. Patients with chronic spinal cord injury who had FES training at least five days per week were likely to have greater increases in BMD from the start than those receiving FES at least three days per week. Other subgroup and sensitivity analyses, with an evaluation of adverse effects, were reported. Authors' conclusions This meta-analysis indicated that early bisphosphonate administration after spinal cord injury effectively reduced sub-lesional bone loss. FES for people with chronic spinal cord injury could significantly increase sub-lesional BMD near the site of maximal mechanical loading. CRD commentary The review question was clear and the inclusion criteria were reported. Several relevant sources were searched. Efforts were made to locate unpublished data thereby reducing the potential for publication bias. No language restrictions were applied, minimising the risk of language bias. Appropriate methods were used to reduce the risk of reviewer error and bias for quality assessment and data extraction, but it was unclear whether similar methods were used for study selection. Appropriate quality assessment tools were used and their results were presented. The review findings appear to be based largely on before-and-after data, which limits any comparison of intervention effectiveness. Small samples and high clinical variation between studies mean that the authors' conclusions may not be reliable. Implications of the review for practice and research Practice: The authors stated that bisphosphonates should be administered immediately after spinal cord injury and continued until a steady state has been reached (approximately two years) to prevent loss of BMD. FES could be used in addition to reverse muscle atrophy and activate bone formation in people with chronic, stable spinal cord injury. Research: The authors did not state any implications for research. Funding Supported by the National Science Council, Taiwan. Bibliographic details Chang KV, Hung CY, Chen WS, Lai MS, Chien KL, Han DS. 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; 8(11): e81124 Indexing Status Subject indexing assigned by NLM MeSH Bone Density /drug effects; Bone Density Conservation Agents /pharmacology /therapeutic use; Diphosphonates /pharmacology /therapeutic use; Electric Stimulation /adverse effects /methods; Humans; Osteoporosis /etiology /therapy; Spinal Cord Injuries /complications; Treatment Outcome AccessionNumber 12013069502 Date bibliographic record published 17/12/2013 Date abstract record published 04/01/2014 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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