Lora Giangregorio

Bone Loss and Muscle Atrophy in Spinal Cord Injury: Epidemiology, Fracture Prediction, and Rehabilitation Strategies

Abstract Summary: Individuals with spinal cord injury (SCI) often experience bone loss and muscle atrophy. Muscle atrophy can result in reduced metabolic rate and increase the risk of metabolic disorders. Sublesional osteoporosis predisposes individuals with SCI to an increased risk of low-trauma fracture. Fractures in people with SCI have been reported during transfers from bed to chair, and while being turned in bed. The bone loss and muscle atrophy that occur after SCI are substantial and may be influenced by factors such as completeness of injury or time postinjury. A number of interventions, including standing, electrically stimulated cycling or resistance training, and walking exercises have been explored with the aim of reducing bone loss and/or increasing bone mass and muscle mass in individuals with SCI. Exercise with electrical stimulation appears to increase muscle mass and/or prevent atrophy, but studies investigating its effect on bone are conflicting. Several methodological limitations in exercise studies with individuals with SCI to date limit our ability to confirm the utility of exercise for improving skeletal status. The impact of standing or walking exercises on muscle and bone has not been well established. Future research should carefully consider the study design, skeletal measurement sites, and the measurement techniques used in order to facilitate sound conclusions.

Body weight supported treadmill training in acute spinal cord injury : impact on muscle and bone

Design:Longitudinal prospective case series.Objective:To evaluate the impact of early introduction postspinal cord injury (SCI) of twice-weekly body-weight supported treadmill training (BWSTT) on muscle and bone.Setting:Centre for Health Promotion and Rehabilitation, McMaster University, Canada.Methods:Five individuals who had sustained traumatic SCI within 2–6 months participated in the study. Bone mineral densities (BMD) of proximal femur, distal femur, proximal tibia and lumbar spine were measured before and after training, as well as muscle cross-sectional area (CSA), BMD and bone geometry at mid-femur and proximal tibia. Serum osteocalcin and urinary deoxypyridinoline were measured at baseline, and after 24 and 48 sessions of training.Results:All participants experienced increased muscle CSAs, ranging from 3.8 to 56.9%. Reductions in BMD were evident in all participants at almost all lower limb sites after training, ranging in magnitude from −1.2 to −26.7%. Lumbar spine BMD changes ranged from 0.2 to −7.4%. No consistent changes were observed in bone geometry. BWSTT did not alter the expected pattern of change in bone biochemical markers over time. The individual with the greatest improvement in ambulatory ability demonstrated the smallest reduction in lower limb BMD. Conversely, the individual who completed the fewest BWSTT sessions demonstrated the greatest reductions in BMD.Conclusions:Twice-weekly BWSTT appeared to partially reverse muscle atrophy after SCI, but did not prevent bone loss. Larger, controlled trials should evaluate whether relative preservation of bone loss occurs with regular BWSTT following acute SCI.Sponsorship:Ontario Neurotrauma Foundation.

A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: Effects on body composition

Abstract Objective To evaluate the effects of functional electrical stimulation (FES)-assisted walking on body composition, compared to a non-FES exercise program in individuals with a spinal cord injury (SCI). Design Parallel-group randomized controlled trial. Methods Individuals with chronic (≥18 months) incomplete SCI (level C2 to T12, AIS C or D) were recruited and randomized to FES-assisted walking (intervention), or aerobic and resistance training (control) sessions thrice-weekly for 16 weeks. Whole body and leg lean mass and whole body fat mass, measured with dual-energy X-ray absorptiometry, and lower-limb muscle cross-sectional area (CSA) and fat CSA, measured with peripheral computed tomography were assessed at baseline, 4 months, and 12 months. Intention-to-treat analyses using repeated measures general linear models were used to assess between-group differences. Results Thirty-four individuals were randomized (17 per group); 27 remained at 12 months. There were no significant main effects of FES-assisted walking on body composition variables in intention-to-treat analyses with group means. There was a significant group-by-time interaction for muscle area from baseline to 12 months (P = 0.04). Intention-to-treat analysis of muscle area change scores between baseline and 12 months revealed a significant difference between groups (mean (SD) muscle area change score 212 (517) mms for FES, −136 (268) mms for control, P = 0.026). There were 13 side effects or adverse events deemed related to study participation (7 intervention, 5 control); most were resolved with modifications to the protocol. One fainting episode resulted in a hospital visit and study withdrawal. Conclusions Thrice-weekly FES-assisted walking exercise over 4 months did not result in a change in body composition in individuals with chronic, motor incomplete C2 to T12 SCI (AIS classification C and D). However, longer-term follow-up revealed that it might maintain muscle area.

Improving Reliability of pQCT-Derived Muscle Area and Density Measures Using a Watershed Algorithm for Muscle and Fat Segmentation

In peripheral quantitative computed tomography scans of the calf muscles, segmentation of muscles from subcutaneous fat is challenged by muscle fat infiltration. Threshold-based edge detection segmentation by manufacturer software fails when muscle boundaries are not smooth. This study compared the test-retest precision error for muscle-fat segmentation using the threshold-based edge detection method vs manual segmentation guided by the watershed algorithm. Three clinical populations were investigated: younger adults, older adults, and adults with spinal cord injury (SCI). The watershed segmentation method yielded lower precision error (1.18%-2.01%) and higher (p<0.001) muscle density values (70.2±9.2 mg/cm3) compared with threshold-based edge detection segmentation (1.77%-4.06% error, 67.4±10.3 mg/cm3). This was particularly true for adults with SCI (precision error improved by 1.56% and 2.64% for muscle area and density, respectively). However, both methods still provided acceptable precision with error well under 5%. Bland-Altman analyses showed that the major discrepancies between the segmentation methods were found mostly among participants with SCI where more muscle fat infiltration was present. When examining a population where fatty infiltration into muscle is expected, the watershed algorithm is recommended for muscle density and area measurement to enable the detection of smaller change effect sizes.

Serum 25(OH)D, PTH and correlates of suboptimal 25(OH)D levels in persons with chronic spinal cord injury

Study design:Cross-sectional cohort study.Objectives:To describe: (1) the prevalence of suboptimal 25-hydroxyvitamin D status (serum 25(OH)D <75u2009nmolu2009l−1) and to identify correlates of vitamin D deficiency; (2) the prevalence of secondary hyperparathyroidism (serum intact parathyroid hormone (PTH)⩾7.0u2009pmolu2009l−1); and (3) the relationships between serum PTH and 25(OH)D in adult men and women with chronic spinal cord injury (SCI).Setting:Outpatient services, including an osteoporosis clinic at a tertiary spinal cord rehabilitation hospital in Ontario.Methods:Serum levels of 25(OH)D and intact PTH were acquired at enrollment. Clinical correlates of suboptimal vitamin D status were collected via interview and chart abstraction, and identified by univariate logistic regression analysis. Pearson correlations were run to assess the relationships between serum PTH and 25(OH)D. Significance was P<0.05.Results:Thirty-nine percent of the cohort, comprised of 62 adult men and women with chronic SCI, had suboptimal serum 25(OH)D levels. Factors associated with suboptimal vitamin D levels included having vitamin D assessed in the winter months (odds ratio (OR)=7.38, P=0.001), lack of a calcium supplement (OR=7.19, P=0.003), lack of a vitamin D supplement (OR=7.41, P=0.019), younger age (OR=0.932, P=0.010), paraplegia (OR=4.22, P=0.016), and lack of bisphosphonate (OR=3.85, P=0.015). Significant associations were observed between serum PTH and 25(OH)D (r=−0.304, P=0.032) and between PTH and C-telopeptide of type I collagen (CTX-I) (r=0.308, P=0.025).Conclusions:Disruption of the vitamin D-PTH axis may contribute to the bone loss seen in the chronic SCI population. The threshold for optimal serum 25(OH)D levels in the chronic SCI population may be higher than in the non-SCI population. Serum 25(OH)D level are likely important risk factors contributing to declining bone mass and increased fracture risk post-SCI.

Musculoskeletal changes in women with spinal cord injury: a twin study.

Bone mineral density (BMD), bone geometry, and muscle cross-sectional area (CSA) were investigated in two sets of monozygotic female twins, where one of each pair had sustained a spinal cord injury (SCI). Twin pair 1 (TP1) and twin pair 2 (TP2) were 32 and 47 yr old and were 7 and greater than 20 yr postinjury, respectively. BMD was measured using dual-energy X-ray absorptiometry. Computed tomography was used to measure volumetric BMD, bone geometry, and muscle CSA of the thigh and calf. For the SCI twin of TP1, BMDs of hip, distal femur, proximal tibia, and spine were 59.5, 46.6, 53.1, and 93.3%, respectively, of values of the noninjured twin. For TP2, corresponding values in the SCI twin were 36.2, 35.9, 39.2, and 62.2%, respectively, of the non-SCI twin. Average muscle CSAs of the SCI twins were 31.2+/-2.3% and 31.0+/-6.1% of the values for their non-SCI twin, indicating that muscle CSAs were reduced by 70%. Among the SCI twins, volumetric BMDs were 83.4+/-2.4% and 87.0+/-3.45% of the non-SCI twins values. Moments of inertia in the SCI twins ranged from 62.4 to 97.9% of the non-SCI twins values at mid-femur and calf. This study reveals that in addition to the declines in muscle CSA and BMD, important changes in bone geometry occur in women after SCI.

An evaluation of the muscle-bone unit theory among individuals with chronic spinal cord injury.

Study design:Cross-sectional observation.Objectives:To explore the association between muscle size and function, and indices of bone strength among a sample of adults with chronic spinal cord injury (SCI).Setting:Ontario, Canada.Methods:Sixty-five participants (n=47 men) with chronic SCI (C1-T12 American Spinal Injury Association Impairment Scale (AIS) A–D) were recruited, mean±s.d. age 49.4±12.8 years and years post-injury 14.3±10.7. Muscle cross-sectional area (CSA) and indices of bone strength at the distal tibia and tibia shaft were measured by peripheral quantitative computed tomography. Muscle CSA was multiplied by tibia length to obtain muscle-bending moment (MBM), a surrogate of torque. Plantar flexor components of the lower-extremity motor scores (pf-LEMS) were used as clinical measures of muscle function. Pearsons correlations (r) were used to determine the strength of relationships.Results:Correlations were found between MBM and indices of bone strength at the distal tibia and tibia shaft (r=0.44–0.56), as well as between pf-LEMS and indices of bone strength at the distal tibia and tibia shaft (r=0.37–0.71). pf-LEMS had a stronger association with bone variables at the distal tibia compared with MBM (r=0.6 vs r=0.4). All relationships between muscle and bone remained significant when controlling for the duration of injury.Conclusion:It appears that lower limb muscle size and function are more strongly correlated with bone strength indices at the distal tibia than at the tibia shaft among individuals with SCI. The relationships between muscle and bone are clinically important, as muscle CSA and strength (motor scores) are potentially amenable to rehabilitation intervention(s).

Build Better Bones With Exercise: Protocol for a Feasibility Study of a Multicenter Randomized Controlled Trial of 12 Months of Home Exercise in Women With a Vertebral Fracture

Background Our goal is to conduct a multicenter randomized controlled trial (RCT) to investigate whether exercise can reduce incident fractures compared with no intervention among women aged ≥65 years with a vertebral fracture. Objectives This pilot study will determine the feasibility of recruitment, retention, and adherence for the proposed trial. Design The proposed RCT will be a pilot feasibility study with 1:1 randomization to exercise or attentional control groups. Setting Five Canadian sites (1 community hospital partnered with an academic center and 4 academic hospitals or centers affiliated with an academic center) and 2 Australian centers (1 academic hospital and 1 center for community primary care, geriatric, and rehabilitation services). Participants One hundred sixty women aged ≥65 years with vertebral fracture at 5 Canadian and 2 Australian centers will be recruited. Intervention The Build Better Bones With Exercise (B3E) intervention includes exercise and behavioral counseling, delivered by a physical therapist in 6 home visits over 8 months, and monthly calls; participants are to exercise ≥3 times weekly. Controls will receive equal attention. Measurements Primary outcomes will include recruitment, retention, and adherence. Adherence to exercise will be assessed via calendar diary. Secondary outcomes will include physical function (lower extremity strength, mobility, and balance), posture, and falls. Additional secondary outcomes will include quality of life, pain, fall self-efficacy, behavior change variables, intervention cost, fractures, and adverse events. Analyses of feasibility objectives will be descriptive or based on estimates with 95% confidence intervals, where feasibility will be assessed relative to a priori criteria. Differences in secondary outcomes will be evaluated in intention-to-treat analyses via independent Student t tests, chi-square tests, or logistic regression. The Bonferroni method will be used to adjust the level of significance for secondary outcomes so the overall alpha level is .05. Limitations No assessment of bone mineral density will be conducted. The proposed definitive trial will require a large sample size. Conclusions The viability of a large-scale exercise trial in women with vertebral fractures will be evaluated, as well as the effects of a home exercise program on important secondary outcomes.

Use of screening to recruitment ratios as a tool for planning and implementing spinal cord injury rehabilitation research

Study design:Descriptive report.Objectives:To describe screening to recruitment (S:R) ratios and discuss their use for planning and implementing research among individuals with spinal cord injury (SCI).Setting:Toronto, Ontario, Canada.Methods:We calculated S:R ratios for SCI research by study methodology and nature of the exposure/intervention for 25 studies previously conducted in a tertiary SCI rehabilitation facility. Study methodologies included ten randomized controlled trials (RCTs), nine cohort studies and six panel studies. Exposures included seven rehabilitation interventions, and three drug studies, ten telephone interviews/chart abstractions (TI/CA) and five surveys. A S:R ratio was calculated for each study methodology, and exposure type, by dividing the number of consenting individuals who underwent screening by the number of eligible recruited participants enrolled in the study.Results:In terms of design, RCTs had the highest median S:R ratio (3:1), followed by cohort studies (2:1) and panel studies (2:1). In terms of intervention type, drug studies had the largest median S:R ratio (5:1), followed in descending order by rehabilitation studies (2:1), TI/CAs studies (2:1) and surveys (2:1).Conclusions:Reported S:R ratios varied substantially with study methodology and the associated study intervention exposure. Awareness of S:R ratios may assist researchers in estimating recruitment timelines, personnel needs and study budgets for a required sample size based on the planned study methodology and intended study exposure. We advocate for the routine reporting of S:R ratios to inform the success of future SCI research.

Evaluating the efficacy of functional electrical stimulation therapy assisted walking after chronic motor incomplete spinal cord injury: effects on bone biomarkers and bone strength

Objectives: To determine the efficacy of functional electrical stimulation therapy assisted walking (FES-T) compared to a conventional aerobic and resistance training (CONV) with respect to bone biomarkers and lower extremity bone strength outcomes among adults with chronic motor incomplete spinal cord injury (SCI). Design: Parallel group randomized controlled trial (www.clinicaltrials.gov - NCT0020196819). Site: Tertiary academic rehabilitation centre in Canada. Methods: Adults with chronic (≥18 months) motor incomplete SCI (C2-T12 AIS C-D) were consented and randomized to FES-T or CONV training for 45 minutes thrice-weekly for 4 months. Osteocalcin (OC), β-cross laps (CTX) and sclerostin were assessed at baseline, and 4 months. Similarly, total hip, distal femur and proximal tibia region bone mineral density (BMD) via DXA (4500A, Hologic Inc. Waltham, MA, USA) and tibia bone quality via pQCT (Stratec XCT-2000, Mezintecknik, Pforzheim, Germany) were assessed at baseline, 4, and 12 months. Between group differences were analyzed using repeated measures general linear models. Results: Thirty-four participants (17 FES-T, 17 CONV) consented and were randomized, 27 participants completed the 4-month intervention and 12-month outcome assessments. Participants in the FES-T arm had a decrease in CTX and a significant increase in OC at intervention completion (P<0.05). Significant biomarker changes were not observed in the CONV group. No within or between group differences from baseline were observed in sclerostin or bone strength. Conclusions: Four months of FES-T improved bone turnover (increase in OC and decrease in CTX) but not bone strength among individuals with chronic SCI. Future, long term FES-T may augment lower extremity bone strength.