Preliminary observations on the administration of a glucagon-like peptide-1 receptor agonist on body weight and select carbohydrate endpoints in persons with spinal cord injury: A controlled case series.

CONTEXT/OBJECTIVE: To describe the effect of semaglutide, a glucagon-like peptide-1 (GLP-1) agonist, to reduce body weight and improve glycemic control in overweight or obese individuals with spinal cord injury (SCI). DESIGN: Open-label, randomized drug intervention case series. SETTING: This study was performed at James J. Peters VA Medical Center (JJP VAMC) and Kessler Institute for Rehabilitation (KIR). PARTICIPANTS: Five individuals with chronic SCI meeting criteria for obesity and abnormal carbohydrate metabolism. INTERVENTION: Administration of semaglutide (subcutaneously once per week) versus no treatment (control) for 26 weeks. OUTCOME MEASURES: Change in total body weight (TBW), fat tissue mass (FTM), total body fat percent (TBF%), and visceral adipose tissue volume (VATvol) was determined at baseline and after 26 weeks using Dual energy X-ray absorptiometry; fasting plasma glucose (FPG) concentration and serum glycated hemoglobin (HbA1C) values were obtained at the same two time points. RESULTS: In 3 participants, after 26 weeks of semaglutide administration, TBW, FTM, TBF%, and VATvol decreased, on average, by 6, 4.4 kg, 1.7%, and 674 cm3, respectively. In addition, values for FPG and HbA1c decreased by 17 mg/dl and 0.2%, respectively. After 26 weeks of observation in the 2 control participants, TBW, FTM, TBF% and VATvol increased on average by 3.3 , 4.5 kg, 2.5%, and 991 cm3, respectively. The average values for FPG and HbA1c also increased by 11 mg/dl and 0.3%, respectively. CONCLUSIONS: Administration of semaglutide for 26 weeks resulted in favorable changes in body composition and glycemic control, suggesting a reduced risk for the development of cardiometabolic disease in obese individuals with SCI.Trial registration: ClinicalTrials.gov identifier: NCT03292315.

Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury.

Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization. OBJECTIVE: To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year. METHODS: Fourteen participants who completed a randomized, double-blinded, placebo-controlled drug trial (parent study: denosumab 60 mg (Prolia, Amgen Inc., n = 8) or placebo (n = 6); administered at baseline, 6, and 12 months) were followed 12 months after the 18 months from baseline primary end point was completed. The BMD of skeletal regions below the SCI at higher risk of fracture was measured [total hip, distal femur epiphysis (DFE), distal femur metaphysis (DFM), and proximal tibia epiphysis (PTE)] by dual energy X-ray absorptiometry. RESULTS: The percent decreases in mean BMD values at all regions of the hip and knee from 18 to 30 months were similar in both the denosumab and placebo groups. However, at 30 months, the absolute values for mean BMD remained significantly higher in the drug treatment than that of the placebo group at the DFM (p = 0.03), DFE (p = 0.04), and PTE (p = 0.05). CONCLUSIONS: In persons with SCI who initiated denosumab treatment during the subacute injury phase and maintained treatment for 1 year, the discontinuation of drug resulted in percent loss of mean BMD similar to that of the placebo group, with absolute mean BMD values at the knee regions at the 12-month follow-up visit significantly higher in the drug treatment than those in the placebo group. These data underscore the need to study continued administration of denosumab after subacute SCI to avoid marked demineralization in the sublesional skeleton upon discontinuation of this agent.

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

Persons 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.