Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury: a randomized, controlled trial

W. Brent Edwards*, Ifaz T. Haider, Narina Simonian, Joana Barroso, Thomas J. Schnitzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


A single infusion of zoledronic acid (ZOL) after acute spinal cord injury (SCI) attenuates bone loss at the hip (proximal femur) and knee (distal femur and proximal tibia) for at least 6 months. The objective of this study was to examine the effects of timing and frequency of ZOL over 2 years. In this double-blind, placebo-controlled trial, we randomized 60 individuals with acute SCI (<120 days of injury) to receive either ZOL 5-mg infusion (n = 30) or placebo (n = 30). After 12 months, groups were again randomized to receive ZOL or placebo, resulting in four treatment groups for year 2: (i) ZOL both years; (ii) ZOL year 1, placebo year 2; (iii) placebo year 1, ZOL year 2; and (iv) placebo both years. Our primary outcome was bone loss at 12 months; compared to placebo, a single infusion of ZOL attenuated bone loss at the proximal femur, where median changes relative to baseline were −1.7% to −2.2% for ZOL versus −11.3% to −12.8% for placebo (p < 0.001). Similarly, the distal femur and proximal tibia showed changes of −4.7% to −9.6% for ZOL versus −8.9% to −23.0% for placebo (p ≤ 0.042). After 24 months, differences were significant at the proximal femur only (−3.2% to −6.0% for ZOL vs. −16.8% to −21.8% for placebo; p ≤ 0.018). Although not statistically significant, median bone density losses suggested some benefit from two annual infusions compared to a single baseline infusion, as well as from a single infusion 12 months after baseline compared to 2 years of placebo; therefore, further investigation in the 12-month to 24-month treatment window is warranted. No unanticipated adverse events associated with drug treatment were observed. In summary, ZOL 5-mg infusion after acute SCI was well-tolerated and may provide an effective therapeutic approach to prevent bone loss in the first few years following SCI.

Original languageEnglish (US)
Pages (from-to)2127-2138
Number of pages12
JournalJournal of Bone and Mineral Research
Issue number11
StatePublished - Nov 2021


  • KNEE

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine


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