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Bone Health

Pharmacologic Therapy: Treatment (1 Year Post-Injury and Beyond)

Author Year; Country
Research Design
Total Sample Size
Methods Outcome

Varghese et al. 2016; India
Level 1

Population: 25 participants (22 men, 3 women) with traumatic chronic SCI; age: 38.3 ± 10.4 years; TPI: 12.2 (6.8) years; 5 cervical/upper thoracic, 20 lower thoracic/lumbar
Treatment: Infusion of zoledronic acid (4 mg) or placebo (saline)
Outcome measures: BMD by DXA at baseline and 12-months post-treatment.

  1. Significant within-group decrease in total hip BMD in placebo group only (0.607±0.073 to 0.491±0.169 g/cm2)
  2. Significant within-group decreases in femoral neck BMD in placebo (0.548±0.111 to 0.480±0.163 g/cm2) and zoledronic acid group (0.576±0.064 to 0.552±0.074 g/cm2)
  3. Significant within-group increases in BMD of distal third of forearm in placebo (0.713±0.031 to 0.747±0.028 g/cm2) and zoledronic acid group (0.717±0.066 to 0.760±0.072 g/cm2)
  4. No significant between-group differences in percentage changes of BMD and BMC
Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%CI) as calculated from pre- and post-intervention data

Bauman et al. 2005b; USA
Level 1

Population: 40 participants (39 men, 1 woman) with complete motor injuries; age 43 ± 13 years; TPI: 12 ± 10 years (range: 1–34 years); 17 participants with tetraplegia and 23 participants with paraplegia.
Treatment: Vitamin D2 analogue, 24 months.
1. Treatment group received calcium 1300 mg daily, vitamin D 800 IU daily, and 1-alpha vitamin D2 4 μg daily (n = 19).
2. Control group received calcium 1300 mg daily, vitamin D 800 IU daily, and placebo in place of vitamin D2.
Outcome measures: BMD by DXA, biomarkers at 6, 12, 18, and 24 months.

  1. Significant changes noted in leg BMD only in the vitamin D2 (treatment) group at 6, 12, 18, and 24 months. There was significant interaction for group by time.
  2. In the vitamin D2 (treatment) group, smoking compromised the response to treatment and changes in BMD.
  3. In the vitamin D2 (treatment) group, urinary marker of bone resorption was significantly reduced, but markers of bone formation were not changed.
Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%CI) as calculated from pre- and post-intervention data

Zehnder et al. 2004b; Switzerland
Level 1

Population: 65 men; age: 38.3 years; TPI: 8.7 years (range, 0.1–29.5); traumatic complete injuries between T1-L3; AIS: A, B.
Treatment: Alendronate for 24 months.
1) 10mg per day plus 500mg calcium per day (n=33) or
2) Calcium alone (500mg per day) (n=32).
Outcome measures: BMD by DXA and bone turnover markers.

  1. Decrease in BMD of the tibia in Calcium group but remained stable in the Treatment group (group difference, p = 0.017). There was no change in wrist BMD and a significant increase in lumbar spine BMD in both groups. BMD of the mid-shaft tibia and hip were maintained in the Treatment group and decreased in the calcium group.
  2. Biochemical markers of bone absorption significantly decreased from baseline in the Treatment group.
Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%CI) as calculated from pre- and post-intervention data

Moran de Brito et al. 2005; Brazil
Level 1

Population: 15 men and 4 women; age: 30.8 (range: 17-47) years; TPI: 49.8 months (range: 13.1–255.7); 18 traumatic and 1 nontraumatic; para/tetraplegia; AIS: A, B, or C.
Treatment: Alendronate for 6 months.
1. 10 mg and Calcium 1000 mg bid (n=10) and
2. Calcium (1000 mg bid) (n=9).
Outcome measures: BMD by DXA

  1. There was a mean increase in upper extremity BMD that was greater in Treatment vs. calcium group although not statistically significant. There were significant differences for total T-score and BMD.
Effect Sizes: Forest plot of standardized mean differences (SMD ± 95%CI) as calculated from pre- and post-intervention data

Gifre et al. 2016; Spain
Level 4
Population: 14 men with traumatic SCI & osteoporosis; age: 39 ±15 (range: 19-65) years; TPI: 15.2 ± 4 (8-21) months; AIS-A/B/C: 12/1/1;
43% paraplegia, 57% tetraplegia
Treatment: Denosumab 60 mg every 6 months up to 12 months
Outcome measures:
Biochemical measurements: Serum creatinine, calcium, phosphate, 25OHD
Bone turnover markers: Bone ALP, P1NP, serum CTX
BMD by DXA at lumbar spine, femoral neck, total hip.
  1. Significant within-group increase in BMD at total hip (2.4±3.6%), femoral neck (3.0±3.6%) and lumbar spine (7.8±3.7%) at 12 months
  2. Significant within-group decreases in ALP (42%), P1NP (-58%) and serum CTX (-57%) at 12 months
  3. BMD changes unrelated to Bone turnover markers or 25OHD changes
  4. No serious treatment-related adverse events were noted.
* All data expressed as mean±SD, unless expressed otherwise.


Evidence for pharmacological treatment of SLOP includes 3 RCTs (Zehnder et al. 2004; Bauman et al. 2005b; Moran de Brioto et al. 2005) (n=124 participants). In these studies, the treatment group experienced improvement or maintenance in bone health at various sites. For the two studies that tested Alendronate, the extent of improvement was greater in the study by Zehnder et al. (2004) who found an increase in BMD at the spine with maintenance of BMD at the hip and tibia. In contrast, Moran de Brioto et al. (2005) only found a non-significant increase in BMD in the upper extremity and a significant increase in total BMD. The difference in response of outcomes could be a result of the younger participants with less severe injuries in the work by Zehnder and coworkers (2004). Bauman and colleagues noted positive results in leg BMD for participants who received vitamin D.

This review has provided conflicting support for using first and second generation oral bisphosphonates for prevention of low bone mass and some support for treatment of low bone mass. Despite the benefits of these medications, they are not without their complications. Oral bisphosphonates must be ingested on an empty stomach, with 4-8oz of water, followed by sitting up for one-hour post ingestion, prior to taking any other food or medication. About 1% of the ingested oral bisphosphonate is absorbed in the upper intestine, yet it remains in the body in an inactive form for several months or years thereafter. Oral bisphosphonate therapy can cause side effects; joint pain, stomach upset and diarrhea being the most frequently reported adverse effects. Intravenous formulations of bisphosphonates are available in monthly, quarterly and annual preparations, and have a greater relative potency. Although their common short-term side effects include fever, low serum calcium and transient decrease in white blood cells, IV preparations are attractive due to the flexibility in dosing regimens, assured adherence to therapy and the reduced relative risk of an adverse upper gastrointestinal event.

Bisphosphonates should be used with caution in pre-menopausal women due to the unknown teratogenic effects of these medications on the fetus during pregnancy. Patients taking acetylsalicylic acid (ASA), corticosteroids or NSAIDS may require gastrointestinal prophylaxis as these medications in combination with bisphosphonates increase the relative risk of developing a gastric ulcer or bleeding. Many questions regarding the safety of these medications among people with SCI and the optimal duration of therapy remain. Zolendronate, an IV bisphosphonate, has been reported to increase the incidence of serious atrial fibrillation resulting in hospitalization or disability among 1-3% of elderly non-SCI patients (HORIZON study, Black et al. 2007). Zolendronate should be used with caution in elderly patients or patients with premorbid atrial fibrillation or arrhythmia secondary to autonomic dysfunction after SCI. The risk of osteonecrosis of the jaw is highest among people with a prior history of cancer or radiotherapy. Both osteonecrosis of the jaw and arrhythmia should be discussed during consent for oral or IV bisphosphonate therapy.

It has been shown that oral bisphosphonates may be taken safely without adverse effects on bone metabolism for 10 years in postmenopausal women (Bone et al. 2004). Data from postmenopausal non-SCI women suggests BMD should be monitored at least alternate years in patients who stop taking oral bisphosphonates; those with a rapid decline in BMD of >10% in two years or >5% from baseline should be switched to alternate treatment or resume bisphosphonate therapy (Colon-Emeric 2006).


There is level 1 evidence (from 1 RCT: Zehnder et al. 2004) that Alendronate 10 mg daily and calcium 500mg orally 3x/day is effective for the maintenance of BMD of the total body, hip and knee region for men with paraplegia.

There is level 1 evidence (from 1 RCT: Bauman et al. 2005b) that vitamin D analog is effective for maintaining leg BMD.

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