TY - JOUR
T1 - Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury
T2 - a randomized, controlled trial
AU - Edwards, W. Brent
AU - Haider, Ifaz T.
AU - Simonian, Narina
AU - Barroso, Joana
AU - Schnitzer, Thomas J.
N1 - Funding Information:
This research was supported by Department of Defense U.S. Army Medical Research and Materiel Command (grant# SC130125; contract# W81XWH‐14‐2‐0193). REDCap is supported by the Northwestern University Clinical and Translational Science (NUCATS) Institute, which is funded in part by a Clinical and Translational Science Award (CTSA) grant UL1TR001422 from the National Institutes of Health (NIH). We thank our colleagues Drs. Alan Anschel, David Chen, Allison Kessler, and Alex Kim at Shirley Ryan AbilityLab for their support in our recruitment efforts; Dr. Elliot Roth and Dr. James Griffith for their role on the Data Safety Monitoring Committee; Stacy Lobos for her efforts with CT analysis; and Drs. Elaine Gregory, Amanpreet Saini, and Frances Leung for their help with recruitment and data collection.
Funding Information:
W. Brent Edwards has received research funding and speaker fees from Amgen. Thomas J. Schnitzer has received research funding from Radius, Amgen, Eli Lilly, and Pfizer as well as consulting fees from Eli Lilly and Pfizer. Ifaz T. Haider, Narina Simonian, and Joana Barroso have no competing interests to declare.
Publisher Copyright:
© 2021 American Society for Bone and Mineral Research (ASBMR).
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - ANTIRESORPTIVE
KW - BISPHOSPHONATE
KW - BONE MINERAL DENSITY
KW - DISUSE OSTEOPOROSIS
KW - KNEE
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U2 - 10.1002/jbmr.4416
DO - 10.1002/jbmr.4416
M3 - Article
C2 - 34278611
AN - SCOPUS:85111546181
VL - 36
SP - 2127
EP - 2138
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 11
ER -