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Selecting Therapy Once an individual with low BMD of the hip or knee region (Z score ≤ -2.0) and an increased risk of lower extremity fragility fracture (≥ 3 risk factors) is identified, the clinician must should consider treatment. For all SLOP therapies, increases in BMD are assumed to be a suitable surrogate out- come for fracture risk reduction, when assessing the effectiveness of SLOP therapy - with “optimal therapy” resulting in an increase in knee region BMD, above the fracture threshold. To date, no SLOP treatment trial has been adequately powered to address fracture risk reduction, among individuals with SCI. The E-Scan survey provides insufficient data to allow us to do anything more than comment on trends in therapy selection. Recent systematic reviews summarize the drug and rehabilitation interventions available for SLOP prevention and treatment. Preventing SLOP Evidence for pharmacological prevention of SLOP after subacute SCI includes several randomized controlled trials (RCT) (see Table 3.0). These studies vary in the choice of of pharmacological intervention, primary outcome measure, duration of follow up, sample sizes and impairment groups. In the majority of studies, bisphosphonate therapy given early post injury reduced the degree of decline, in hip and knee region bone mass, when compared with a control group. Shapiro and colleagues13 tested the effect of once-yearly IV Zoledronate, with significant improvements reported in BMD at the hip, at six months, that returned to baseline values at 12 months. The control group, on the placebo treatment, lost bone over the 12 months. Bubbear et al.14 also showed that a once-yearly IV Zolendronate infusion ameliorated deterioration in bone mass, at the spine and hip, over 12 months. Investigators also highlighted the added benefits of a once-yearly IV administration of bisphosphonate, to eliminate issues surrounding poor patient adherence, and the adverse gastrointestinal effects associated with oral bisphosphonate therapies. Although there is evidence that bisphosphonates may reduce bone resorption, current medications do not entirely preserve lower extremity BMD. Table 3.0 Summary of SLOP Bisphosphonate Prevention Trials Treatment of SLOP Level 1b evidence supports alendronate for treatment of SLOP, among individuals with chronic motor complete paraplegia (Table 4.0). Using a randomized, open-label design, Zehnder et al.15 evaluated the effectiveness of alendronate 10 mg daily, and calcium 500 mg daily, versus calcium 500 mg daily (alone) for 24 months on BMD, after SCI. The study cohort consisted of 55 men with motor complete SCI (para/tetraplegia, AIS A or B), living in Switzerland. Injury duration ranged from one month to 29 years, post SCI, with group means of 10 years, post injury. The primary outcome was a change in tibia epiphysis aBMD, from baseline. Key findings included an 8.0% decline in tibia epiphysis BMD, in the control group, and relative maintenance of tibia epiphysis BMD (-2.0%), in the treatment group (p < .001). Thus, individuals with SLOP and motor complete injury (AIS A or B) may be treated with alendronate (70 mg weekly), calcium, and vitamin D supplements. Alendronate should be used with caution, in individuals with spinal cord lesions at or above T6, as esophageal dysmotility is common after SCI, and increases the risk of esophageal erosions. Alendronate may also elicit atrial fibrillation, among individuals with SCI above T6, and a propensity for autonomic dysfunction. No clinical trials, to date, evaluate drug treatments of SLOP, among individuals with motor incomplete injuries (AIS C and D). Recent p-QCT data, describing changes in lower extremity cortical and trabecular volumetric BMD, over time, suggest there is a therapeutic window, two to eight years post injury, during which antiresorptive therapies, like the bisphosphonates, are most likely to be effective for SCI patients. Table 4.0 Summary of Bisphosphonate Treatment Trials Author, Year Compound Relati ve Potenc y PEDro N Duration BMD Bubbear, 2011 Zolendronate ≥ 5000 6 14 12/12 + Craven, 2008 Risedronate 5,000 11 34 12/12 - Gilchrist, 2007 Alendronate 1000 7 31 12/12 + Gilchrist, 2007 Alendronate 1000 7 31 12/12 + Bauman, 2005 Pamidronate 100 10 14 12/12 - Nance, 1999 Pamidronate 100 13* 24 6/12 + Pearson, 1997 Etidronate 1 8 13 4.5/12 +AIS D/ - AIS A-C Chappard, 1995 Tiludronate 10 9 20 3/12 Biopsy Minaire, 1978 Clodronate 10 7 21 3.5/12 + Minaire, 1981 Clodronate 10 10 21 3.5/12 Biomarker Author, Year Compound Relati ve Potenc y PEDro N Duration BMD Zehnder, 2004 Alendronate 1000 7 65 24/12 + Bauman, 2005 Vitamin D N/A 10 40 24/12 + Moran de Brito, 2005 Alendronate 1000 6 19 6/12 No significant change SKELETAL INTEGRITY | BODY STRUCTURE AND FNUCTION 119


L - Skeletal Integrity
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