Interventions With Bone Biomarker Outcomes

As biomarker science improves, the utility of urinary and serum biomarkers of bone turnover continues to increase. While BMD is considered the gold standard outcome measure for bone health interventions, this outcome is not always available. In particular, retrospective studies may not have access to BMD data, and may, therefore, report only biomarker outcomes. Table 18 describes several such studies.

Author Year; Country
Research Design
Total Sample Size
Methods Outcome
Chen et al. 2001;
Case series
Level 4
Population: 21 participants (17 men, 4 women) with acute SCI; age: 34 (range, 16- 78) years; TPI: 26 days (range: 6 to 122); AIS A (n = 17), AIS B (n = 2), AIS C or D (n = 2).
Treatment: 0.5 µg calcitriol daily x 6 days; 1250 mg calcium carbonate BID x 6 days; 30 mg pamidronate intravenous daily x 3 days (administered on days 4, 5, and 6 of study)
Outcome measures: Within 2 weeks prior to baseline, and again within 2 weeks following study completion: 24-hour urine calcium and creatinine; spot urine NTX; serum calcium, phosphorus, intact PTH, 25-D, 1,25-D.
  1. Calcitriol-pamidronate therapy decreased urinary NTx excretion by 71% (p < 0.001), and urinary calcium excretion by 73% (p < 0.001).
  2. Calcitriol-pamidronate therapy increased serum PTH (p < 0.05) and 1,25-D (p < 0.005).
  3. Post-therapy hypocalcemia or hypophosphatemia occurred in 44% (p < 0.01) and 53% (p < 0.01) of participants, respectively.
Mechanick et al. 2006;
Case series
Level 4
Population: 32 adults (25 men, 7 women) with acute traumatic SCI; age: 42 years; paraplegia (n=8), tetraplegia (n=13); AIS A (n=22), AIS B (n=5), AIS C (n=5).
Treatment: calcium 1000 mg daily and calcitriol 0.25 µg daily x 17 days, pamidronate 90 mg intravenous on day 4
Outcome measures: Serum calcium, phosphorus, and albumin; urinary calcium and NTX, serum intact PTH, 25-D, 1,25-D
  1. Single-dose calcitriol-pamidronate therapy decreased urinary NTX excretion by 64% (p<0.001) and urinary calcium excretion by 50% (p<0.002) in acute SCI.
  2. Post-therapy hypocalcemia or hypophosphalemia occurred in 75% (p<0.02) and 22% (p<0.02) of participants, respectively.
  3. Single-dose pamidronate is associated with increased incidence of fever (78%) compared to 30 mg daily x 3 days dosing regimen (20%).
Bauman et al. 2009;
Case series
Level 4
N = 8
Population: 8 men with chronic SCI; age: 34 ± 7 years (range: 23–43); TPI: 12 ± 8 years (range: 3–27); paraplegia (n=6), tetraplegia (n=2); low vitamin D (25[OH]D ≤ 20 ng/mL) and/or elevated serum PTH (>55 pg/mL).
Treatment: Calcium gluconate bolus (0.025 mmol elemental calcium/kg) over 20 min followed by calcium gluconate infusion (0.025 mmol/kg/hr) for 6 hours.
Outcome measures: Serum total calcium, creatinine, NTX, and PTH at baseline, 2, 4, and 6 hours post-infusion.
  1. At 2 hr time point, PTH dropped from 70 ± 25 pg/mL to 18 ± 12 pg/mL, and NTx dropped from 21 ± 8 nM bone collagen equivalent (BCE) to 17 ± 5 nM BCE.
  2. Calcium gluconate infusion reduced bone collagen catabolism during calcium infusion.
* All data expressed as mean±SD, unless expressed otherwise.


Two retrospective case series studies (Chen et al. 2001; Mechanick et al. 2006) provide Level 4 evidence supporting the use of calcitriol-pamidronate therapy to reduce urinary excretion of calcium and NTX in acute SCI, which are biomarkers of bone resorption. Single-dose infusion of pamidronate was associated with increased incidence of fever compared to infusion on three consecutive days. However, single-dose pamidronate may be a more efficient use of patients’ time during ever-shorter inpatient rehabilitation stays.

One study (Bauman et al. 2009) provided Level 4 evidence that calcium gluconate infusion may reduce transient bone collagen catabolism in men with chronic SCI.


There is Level 4 evidence (Chen et al. 2001; Mechanick et al. 2006) to support the use of calcitriol-pamidronate therapy to reduce bone resorption in acute SCI.