Zoledronic acid attenuates bone loss following complete traumatic spinal cord injury
1Oleson C, 1Marino R, 2Formal C, 3Modlesky C
1Thomas Jefferson University, Philadelphia, PA, United states; 2Magee Rehabilitation Hospital, Philadelphia, PA, United states; 3University of Georgia, Athens, GA, United states
Objectives: To examine differences in bone markers and bone density in subjects receiving IV zoledronic acid (ZA) versus placebo2-3 weeks following complete traumatic spinal cord injury (SCI).
Setting: Two inpatient acute rehabilitation units
Methods; Fifteen subjects with acute traumatic SCI, neurologic levels C4-T10, ASIA Impairment Scale A, received zoledronic acid 5 mg vs normal saline (2:1 ratio) in a double blind, placebo-controlled investigation. Study drug was given 12-21 days post injury. Serum C-telopeptide (CTX), a marker of bone loss, procollagen N-1 terminal propeptide (P1NP), a marker of bone formation, and DXA scans were obtained at baseline, 2 weeks post-infusion (labs only), 4 and 12 months post injury. All subjects received supplemental vitamin D to maintain levels >32 ng/ml and received serum calcium based on dietary intake, such that the combination of oral supplements and dietary sources equaled 1200 mg of calcium daily. Serum Vitamin D25-OH was obtained at the same times as bone markers as well as at 8 months post injury, while serum calcium, creatinine and other electrolytes was checked in the immediate post infusion setting as well as the above time points. All subjects received acute inpatient rehabilitation.
Results: Subjects consisted of 13 men and 2 women; racial mix was 60% white, 26.7% black, 6.7% Hispanic, and 6.7% Asian. Results illustrate marked differences in 10 treatment and 5 control patients, based on CTX values at 1 month and DXA results in the total hip, femoral neck and distal femur at 4 months. Ten ZA subjects experienced a 2 week post-infusion decline in CTX values of 50-75%, suggesting bone sparing. In contrast, control subjects demonstrated 1% reduction (sparing) to 119% increase in CTX, indicating a significant bone loss during this time. All P1NP values were within normal limits. DXA results 4 months post study drug showed that ZA subjects had a mean of 2.91% loss in total hip BMD, compared with the 5 controls who had a mean BMD loss of 12.7% (p<0.02). In the femoral neck, ZA subjects had an average gain of 0.46% BMD versus controls with 9.61% loss (p=0.031). In the distal femur, ZA subjects had a mean loss of 2.51% compared with 5 controls averaging 6.74% (NS, p=0.179). One outlier in the ZA group of 10 occurred due to suboptimal imaging position, without whom the remaining 9 subjects had an average gain in BMD of 0.042% (p=0.023). Proximal tibia changes in BMD averaged -0.074% for ZA patients and -8.558% for controls (NS, p=0.279). Outcomes at 12 months remain pending in 2 subjects, and thus not reported here.
Conclusion: Given the drug/placebo ratio, it appears that administration of ZA demonstrated greatly reduced bone markers and relatively preserved bone density in hip and distal femur but not proximal tibia, following administration of ZA.
Support: NIDILRR grant 080-26000-R84004
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