In patients with acute spinal cord injury (SCI) previously treated with denosumab, bone mineral density (BMD) in specific skeletal regions is significantly different 12 months after discontinuation of denosumab compared with patients who received placebo. These findings were published in Osteoporosis International.
This double-blind, placebo-controlled trial included 26 patients who had experienced SCI within 90 days of selection. Participants were randomly assigned to receive either subcutaneous denosumab (60 mg) or placebo at baseline, 6 months, and 12 months. The primary outcomes were BMD at the distal femur metaphysis (DFM) and distal femur epiphysis (DFE) 18 months after initial drug/placebo treatment, as measured by dual-energy x-ray absorptiometry (DXA). The follow-up visit occurred at 18 months.
Secondary outcomes included BMD of the proximal tibia epiphysis (PTE), femoral neck, and total hip (TH). Participants who completed the 18-month follow-up visit and missed no doses during the parent randomized, controlled trial (RCT) were then eligible to complete an observational follow-up study to examine BMD differences between the denosumab group and placebo group via DXA 1 year after the RCT (considered month 30 of the study). Of the original 26 participants who participated in the RCT, 14 completed this follow-up study.
BMDs were significantly different between the denosumab and placebo groups at the DFM (P =.04), DFE (P =.008), PTE (P =.03), and TH (P =.03) at the 30-month mark of the study. Additionally, a significant time effect for all skeletal areas was noted, indicating that both groups experienced some amount of BMD loss. At the 1-year follow-up visit, the absolute values for BMD were significantly higher in the denosumab group than in the placebo group at the DFM (1.059±0.114 g/cm2 vs 0.844±0.212 g/cm2; P =.03), DFE (1.247±0.215 g/cm2 vs 0.953±0.259 g/cm2; P =.04), and PTE (0.878±0.177 g/cm2 vs 0.655±0.207 g/cm2; P =.05). The percent decreases in mean BMD at all investigated regions 1 year after the end of the study (the 30-month mark) were similar in the denosumab and placebo groups.
The study has several limitations. First, the small sample size limits the power of the study. The study is also limited by its short duration and there is no measurement of biomarkers of bone turnover, which could help tailor treatment with bone-preserving drugs.
“Our work strongly suggests the need to continue administration of denosumab after acute SCI for an indeterminate period of time to avoid rapid and marked deterioration of the sublesional skeleton,” the study authors wrote. They also noted that studies of greater size and power on this topic would be beneficial in further elucidating the outlook and nature of post-SCI treatment with denosumab and other bone-preserving agents. Additionally, they found possible anecdotal benefits for mechanical stimulation of the lower limbs via activities such as functional electrical stimulation cycling and powered exoskeleton-assisted walking in combination with an agent such as denosumab in cases of SCI.
Cirnigliaro CM, La Fountaine MF, Parrott JS, et al. Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury. Osteoporos Int. Published online February 3, 2023. doi:10.1007/s00198-023-06679-w