Christopher M. Cirnigliaro

Introduction Persons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that is directly associated with increased risk of long-bone fractures. There is a paucity of research that has successfully implemented rehabilitation and/or exercise training interventions to mitigate bone loss after acute SCI or reverse bone loss that has already occurred in chronic SCI. This paper describes a research protocol to compare the effect of exoskeletal-assisted walking (EAW) alone versus EAW plus transcutaneous spinal cord stimulation (EAW+tSCS) on bone density, geometry and strength in a cohort of chronic SCI participants. Methods and analysis After meeting eligibility criteria and completing baseline testing, sixteen participants will be block randomised into the EAW alone group or the EAW+tSCS combined group (n=8 each group). Each group will receive a total of 108 overground training sessions (60 min sessions, 3 times a week, for 36 weeks) for the 9-month training period. Imaging for bone density and geometry by dual-energy X-ray absorptiometry and peripheral quantitative CT will be performed prior to starting the intervention (baseline), after 72 training sessions, and again after 108 sessions in each of the intervention arms. CT imaging of both lower extremities will be performed at baseline and at the 9-month time point in each of the intervention arms. Finite element models of bone loading will be generated based on three-dimensional (3D) reconstruction of bone architecture from CT imaging prior to and 9 months after the intervention. Ethics and dissemination This study is currently approved by the Kessler Foundation and James J. Peters VA Medical Center Institutional Review Board. A member of the research team will review and explain the study consent form and will have all eligible participants sign prior to participation in the study. Results from this study will be disseminated to clinicians and researchers in the SCI community at national and international conferences. Trial registration number NCT03096197.

Context/ObjectiveTo identify cardiometabolic (CM) measurements that cluster to confer increased cardiovascular disease (CVD) risk using principal component analysis (PCA) in a cohort of chronic spinal cord injury (SCI) and healthy non-SCI individuals.ApproachA cross-sectional study was performed in ninety-eight non-ambulatory men with chronic SCI and fifty-one healthy non-SCI individuals (ambulatory comparison group). Fasting blood samples were obtained for the following CM biomarkers: lipid, lipoprotein particle, fasting glucose and insulin concentrations, leptin, adiponectin, and markers of inflammation. Total and central adiposity [total body fat (TBF) percent and visceral adipose tissue (VAT) percent, respectively] were obtained by dual x-ray absorptiometry (DXA). A PCA was used to identify the CM outcome measurements that cluster to confer CVD risk in SCI and non-SCI cohorts.ResultsUsing PCA, six factor-components (FC) were extracted, explaining 77% and 82% of the total variance in the SCI and non-SCI cohorts, respectively. In both groups, FC-1 was primarily composed of lipoprotein particle concentration variables. TBF and VAT were included in FC-2 in the SCI group, but not the non-SCI group. In the SCI cohort, logistic regression analysis results revealed that for every unit increase in the FC-1 standardized score generated from the statistical software during the PCA, there is a 216% increased risk of MetS (P = 0.001), a 209% increased risk of a 10-yr. FRS & GE; 10% (P = 0.001), and a 92% increase in the risk of HOMA2-IR & GE; 2.05 (P = 0.01).ConclusionApplication of PCA identified 6-FC models for the SCI and non-SCI groups. The clustering of variables into the respective models varied considerably between the cohorts, indicating that CM outcomes may play a differential role on their conferring CVD-risk in individuals with chronic SCI.

Background: The prevention of lower extremity fractures and fracture-related morbidity and mortality is a critical component of health services for adults living with chronic spinal cord injury (SCI). Methods: Established best practices and guideline recommendations are articulated in recent international consensus documents from the International Society of Clinical Densitometry, the Paralyzed Veterans of America Consortium for Spinal Cord Medicine and the Orthopedic Trauma Association. Results: This review is a synthesis of the aforementioned consensus documents, which highlight the pathophysiology of lower extremity bone mineral density (BMD) decline after acute SCI. The role and actions treating clinicians should take to screen, diagnose and initiate the appropriate treatment of established low bone mass/osteoporosis of the hip, distal femur or proximal tibia regions associated with moderate or high fracture risk or diagnose and manage a lower extremity fracture among adults with chronic SCI are articulated. Guidance regarding the prescription of dietary calcium, vitamin D supplements, rehabilitation interventions (passive standing, functional electrical stimulation (FES) or neuromuscular electrical stimulation (NMES)) to modify bone mass and/or anti-resorptive drug therapy (Alendronate, Denosumab, or Zoledronic Acid) is provided. In the event of lower extremity fracture, the need for timely orthopedic consultation for fracture diagnosis and interprofessional care following definitive fracture management to prevent health complications (venous thromboembolism, pressure injury, and autonomic dysreflexia) and rehabilitation interventions to return the individual to his/her pre-fracture functional abilities is emphasized. Conclusions: Interprofessional care teams should use recent consensus publications to drive sustained practice change to mitigate fracture incidence and fracture-related morbidity and mortality among adults with chronic SCI.

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)...

Summary 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.

Persons with spinal cord injury (SCI) have neurogenic bowel disorders characterized by difficulty with evacuation (DWE), fecal incontinence, and discoordination of defecation. Six medically stable in-patients with SCI with a mean age of 57 ± 10 years (range: 39–66 years) and time since injury of 18 ± 17 years (range: 3–47 years) were investigated. Standard of care (SOC) for bowel care was followed by two weeks of SOC plus neostigmine (0.07 mg/kg) and glycopyrrolate (0.014 mg/kg) administered transcutaneously by iontophoresis thrice weekly for two weeks while patients continued to receive SOC. The primary endpoint was time to bowel evacuation. Body weights and abdominal radiographs were obtained. Ten questions related to bowel function and the Treatment Satisfaction Questionnaire for Medication were acquired after each arm. Bowel evacuation time decreased after the dual drug intervention arm (106.9 ± 68.4 vs. 40.8 ± 19.6 min; p < 0.0001). Body weight decreased (2.78 ± 0.98 kg; p < 0.0001), a finding confirmed on abdominal radiograph. Both questionnaires demonstrated improvement after the dual drug intervention arm. No major adverse events occurred. The addition of neostigmine and glycopyrrolate by transcutaneous administration to SOC for bowel care in persons with SCI and DWE resulted in the safe, effective, and predictable bowel evacuation with subjective improvement in bowel care.