Table 1. Summary of studies which used bisphosphonate analogues or functional electrical stimulation (FES) to treat bone mineral density (BMD) loss in patients after spinal cord injury (SCI).
| Authors, year | Sample characteristic | Sample number | Study design | Double blind | Intention to treat | Treatment | Frequency | Duration | Device for BMD measurement | Site of BMD measurement | Quality Assessments |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies using bisphosphonate analogues to attenuate bone loss in SCI patients | |||||||||||
| Pearson et al, 1997 | Acute SCI. Post-injury duration: within 6 weeks. Injury level: T: C5-T12; C: C6-T12. Age: T: 33.6 ± 4.5 years; C: 35.6 ± 11.6 years | T: 5 (4 males, 1 female); C: 6 (all males) | RCT | No | No | Etidronate, 800 mg, oral | Once daily | 2 weeks for each cycle; total two cycles of treatments separated by 13 weeks | DEXA | Distal femur | 1* |
| Nance et al, 1999 | Acute SCI. Post-injury duration: within 6 weeks. Injury level: T: C4-L1; C: C6-L1. Age: T: 31.8 ± 8.7 years; C: 34.4 ± 12.1 years | T: 12 (11 males, 1 female); C: 7 (all males) | Quasi-experimental study | No | No | Pamidronate, 30 mg, IV | Once per month | 6 months | DEXA | Whole lower extremity | 0* |
| Zehnder et al, 2004 | Mainly chronic SCI. Post-injury duration: T: 10.8 ± 1.4 years; C: 9.9 ± 1.7 years. Injury level: T1-L3. Age: T: 38.8 ± 1.5 years; C: 37.9 ± 2.2 years | T: 29 (all males); C: 26 (all males) | RCT | No | No | Alendronate, 10 mg, oral | Once daily | 24 months | DEXA | Proximal tibia | 2* |
| Moran et al, 2005 | Chronic SCI. Post-injury duration: T: 61.0 ± 77.3 months; C: 38.7 ± 17.1 months. Injury level: not mentioned. Age: T: 30.9 ± 9.5 years; C: 30.8 ± 9.9 years | T: 9 (1 dropout from 8 males, 2 females); C: 8 (1 dropout from 7 males, 2 females) | RCT | No | No | Alendronate,10 mg, oral | Once daily | 6 month | DEXA | Whole lower extremity | 1* |
| Bauman et al, 2005 | Acute SCI. Post-injury duration: 44 ± 18 days. Injury level: T: 3 tetraplegia, 3 paraplegia; C: 2 tetraplegia, 3 paraplegia. Age: T: 39 ± 15 years; C: 30 ± 8 years | T: 6 (4 males, 2 females); C: 5 (4 males, 1 female) | RCT | Yes | No | Pamidronate, 60 mg IV | at baseline and then at 1, 2, 3, 6, 9, and 12 months | 12 month | DEXA | Distal femur | 4* |
| Gilchrist et al, 2007 | Acute SCI. Post-injury duration: within 10 days. Injury level: C4-L2. Age: 17-55 years | T: 12 (3 dropouts from 10 males, 5 females); C: 13 (3 dropouts from 12 males, 4 females) | RCT | Yes | No | Alendronate, 70 mg, oral | Once per week | 12 months | DEXA | Femoral shaft | 5* |
| Shapiro et al, 2007 | Acute SCI. Post-injury duration: < 12 weeks. Injury level: C2-T12. Age: T: 30.1 ± 14.2 years; C: 28.4 ± 9.4 years | T: 8; C: 9 (gender not mentioned) | RCT | Yes | No | Zoledronic acid, 4 or 5 mg, IV | At baseline | Once | DEXA | Femoral neck | 5* |
| Bubbear et al, 2011 | Acute SCI. Post-injury duration: within 3 months. Injury level: T: C4-L3; C: C6-T8. Age: 31.6 ± 7.7 years; C: 27.0 ± 14.4 years | T: 6 (1 dropout from 4 males, 3 females); C: 5 (2 dropouts from 5 males, 2 females) | RCT | No | No | Zoledronic acid, 4mg, IV | At baseline | Once | DEXA | Greater trochanter | 3* |
| Studies using FES to attenuate bone loss in SCI patients | |||||||||||
| Leeds et al, 1990 | Chronic SCI. Post-injury duration: 5.17 ± 2.40 years. Injury level: C4-C6. Age: 23.67 ± 3.20 years | 6 (all males) | Longitudinal follow-up study | No | Yes | FES cycling ergometry | 3 sessions per week. Gradually increased training time to 30 mins per session | 6 months | DEXA | Femoral trochanter | 4† |
| BeDell et al, 1996 | Chronic SCI. Post-injury duration: > 2 years. Injury level: C5-T12. Age: 34 ± 6 years | 12 (all males) | Longitudinal follow-up study | No | Yes | FES cycling ergometry | 30 mins, three times per week | 24 sessions | DEXA | Femoral neck | 4† |
| Bloomfield et al, 1996 | Chronic SCI Post-injury duration: T: 6 ± 1.2 years; C: 8.3 ± 2.3 years. Injury level: T: C5-T7; C: C4-T12. Age: T: 28.2 ± 1.8 years; C: 34.4 ± 2.5 years | T: 9 (5 males, 4 females); C: 8 (5 males, 3 females) | Quasi-experimental study | No | Yes | FES cycling ergometry | 3 sessions per week | 9 months | DEXA | Distal femur | 5* |
| Mohr et al, 1997 | Chronic SCI. Post-injury duration: 12.5 ± 2.7 years. Injury level: C6-T4. Age: 35.3 ± 2.3 years | 10 (8 males, 2 females) | Longitudinal follow-up study | No | Yes | FES cycling ergometry | 30 mins per day, 3 days per week | 12 months | DEXA | Proximal tibia | 4† |
| Belanger et al, 2000 | Chronic SCI Post-injury duration: 9.6 ± 6.6 years. Injury level: C5-T5. Age: 32.4 ± 5.9 years | T: 14 (11 males, 3 females); C: 14 age and sex-matched healthy individuals | Longitudinal follow-up study | No | No | FES plus resistive training | 1 hour per day, 5 days per week | 6 months | DEXA | Distal femur | 4† |
| Eser et al, 2003 | Acute SCI. Post-injury duration: T: 4.5 ± 2.9 weeks; C: 4.6 ± 2.9 weeks. Injury level: T: C5-T10; C: C5-T12. Age: T: 32.9 ± 11.5 years; C: 33.8 ± 13.0 years | T: 19 (17 males, 2 females) ; C: 19 (17 males, 2 females) | Quasi-experimental study | No | No | FES cycling ergometry | 30 mins per day, 3 days per week | Average 6 months | CT scanner | Proximal tibia | 5* |
| Chen et al, 2005 | Chronic SCI. Post-injury duration: > 2 years and 7 months. Injury level: C5-T8. Age: 28.67 ± 3.77 years | 15 (all males) | Longitudinal follow-up study | No | Yes | FES cycling ergometry | 30 mins per day, five days per week | 6 months | DEXA | Distal femur | 4† |
| Clark et al, 2007 | Acute SCI. Post-injury duration: within two days. Injury level: T: C4-T10; C: C5-T12. Age: T: 30.0 ± 8.9 years; C: 34.8 ± 11.2 years | T: 23; C: 10 (gender not mentioned) | Longitudinal follow-up study | No | Yes | FES plus resistive training | 15-min to each leg twice daily, 5 days per week | 5 months | DEXA | Whole lower extremity | 5† |
| Frotzler et al, 2008 | Chronic SCI. Post-injury duration: 11.0 ± 7.1 years. Injury level: T3-T9. Age: 41.9 ± 7.5 years | 11 (9 males, 2 females) | Longitudinal follow-up study | No | No | FES cycling ergometry | 60 mins per session. 5 sessions per week | 12 months | Peripheral quantitative CT scanner | Distal femur | 4† |
| Griffin et al, 2009 | Chronic SCI. Post-injury duration: 11.0 ± 3.1 years. Injury level: C4-T7. Age: 40.0 ± 2.4 years | 18 (13 males, 5 females) | Longitudinal follow-up study | No | Yes | FES cycling ergometry | 2-3 times per week | 10 weeks | DEXA | Not mentioned | 4† |
| Lai et al, 2010 | Acute SCI. Post-injury duration: 26-52 days. Injury level: C5-T10. Age: T: 28.9 ± 5.3 years; C: 28.2 ± 5.7 years | T: 12 (10 males, 2 females); C: 12 (10 males, 2 females) | Longitudinal follow-up study | No | Yes | FES cycling ergometry | 3 times per week | 3 months, and then suspend for subsequent 3 months | DEXA | Distal femur | 5† |
Note: * Quality scores derived from the Jadad scale. † Quality scores derived from the Newcastle-Ottawa Scale. Abbreviation: T, treatment group; C, control group; RCT: randomized controlled trial; DEXA: dual-energy X-ray absorptiometry; IV: intravenous.