Administration of Denosumab Preserves Bone Mineral Density at the Knee in Persons With Subacute Spinal Cord Injury: Findings From a Randomized Clinical Trial

JBMR Plus - Tập 4 Số 8 - 2020
Christopher M. Cirnigliaro1, Michael F. La Fountaine2,1,3, J. Scott Parrott4, Steven Kirshblum5,6,7, Cristin McKenna6,7, Susan J. Sauer7, Sue A. Shapses8, Lihong Hao8, Isa A. McClure7, Joshua C. Hobson9, Ann M. Spungen1,10, William A. Bauman1,10
1Department of Veterans Affairs Rehabilitation Research & Development Service National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
2Department of Physical Therapy, School of Health and Medical Sciences, Seton Hall University, South Orange, NJ, USA
3Departments of Medical Sciences and Neurology, Hackensack Meridian School of Medicine at Seton Hall University, Nutley, NJ, USA
4Department of Interdisciplinary Studies, School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ, USA
5Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, NJ, USA
6Kessler Foundation, West Orange, NJ, USA
7Kessler Institute for Rehabilitation West Orange, NJ USA
8Department of Nutritional Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, USA
9Department of Kinesiology and Applied Physiology, University of Delaware, Newark DE USA
10Departments of Medicine and Rehabilitation and Human Performance, Icahn School of Medicine at Mount, Sinai, New York, NY, USA

Tóm tắt

ABSTRACTPersons with neurologically motor‐complete spinal cord injury (SCI) have a marked loss of bone mineral density (BMD) of the long bones of the lower extremities, predisposing them to fragility fractures, especially at the knee. Denosumab, a commercially available human monoclonal IgG antibody to receptor activator of nuclear factor‐κB ligand (RANKL), may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty‐six SCI participants with subacute motor‐complete SCI were randomized to receive either denosumab (60 mg) or placebo at baseline (BL), 6, and 12 months. Areal bone mineral density (aBMD) by dual energy x‐ray absorptiometry (DXA) at 18 months at the distal femur was the primary outcome and aBMD of the proximal tibia and hip were the secondary outcomes analyzed in 18 of the 26 participants (denosumab, n = 10 and placebo, n = 8). The metrics of peripheral QCT (pQCT) were the exploratory outcomes analyzed in a subsample of the cohort (denosumab, n = 7 and placebo n = 7). The mean aBMD (±95% CI) for the denosumab versus the placebo groups demonstrated a significant group × time interactions for the following regions of interest at BL and 18 months: distal femoral metaphysis = mean aBMD 1.187; 95% CI, 1.074 to 1.300 and mean aBMD 1.202; 95% CI, 1.074 to 1.329 versus mean aBMD 1.162; 95% CI, 0.962 to 1.362 and mean aBMD 0.961; 95% CI, 0.763 to 1.159, respectively (p < 0.001); distal femoral epiphysis = mean aBMD 1.557; 95% CI, 1.437 to 1.675 and mean aBMD 1.570; 95% CI, 1.440 to 1.700 versus mean aBMD 1.565; 95% CI, 1.434 to 1.696 and mean aBMD 1.103; 95% CI, 0.898 to 1.309, respectively (p = 0.002); and proximal tibial epiphysis = mean aBMD 1.071; 95% CI, 0.957 to 1.186 and mean aBMD 1.050; 95% CI, 0.932 to 1.168 versus mean aBMD 0.994; 95% CI, 0.879 to 1.109 and mean aBMD 0.760; 95% CI, 0.601 to 0.919, respectively (p < 0.001). Analysis of pQCT imaging revealed a continued trend toward significantly greater loss in total volumetric BMD (vBMD) and trabecular vBMD at the 4% distal tibia region, with a significant percent loss for total bone mineral content. Thus, at 18 months after acute SCI, our findings show that denosumab maintained aBMD at the knee region, the site of greatest clinical relevance in the SCI population. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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