Functional electrical stimulation (FES)-assisted rowing combined with zoledronic acid, but not alone, preserves distal femur strength and stiffness in people with chronic spinal cord injury.

We investigated the effect of 12 months of functional electrical stimulation-assisted rowing with and without zoledronic acid (ZA) on computationally estimated bone strength and stiffness in individuals with spinal cord injury. We found that rowing with ZA, but not rowing alone, improved stiffness at the distal femur, but not the proximal tibia. INTRODUCTION: People with spinal cord injury (SCI) have high fracture risk at the knee after the injury. Therapies that prevent bone loss or stimulate an anabolic response in bone have been proposed to reduce fractures. Zoledronic acid (ZA) is a potent bisphosphonate that inhibits osteoclastic resorption. Functional electrical stimulation (FES)-assisted rowing is a potentially osteogenic exercise involving mechanical stimulation to the lower extremities. Here, we investigated the effect of FES-assisted rowing with and without ZA on bone strength and stiffness in individuals with SCI. METHODS: Twenty individuals from a cohort of adults with SCI who participated in a clinical trial were included in the study. CT scans of their knees before and after the intervention were converted to finite element models. Bone failure strength (Tult) and stiffness were calculated at the proximal tibia and distal femur. RESULTS: Tult at the distal femur increased 4.6% among people who received rowing + ZA and decreased 13.9% among those with rowing only (p < 0.05 for group). Torsional and compressive stiffness at the femur metaphysis increased in people with rowing + ZA (+ 3 to +4%) and decreased in people with rowing only (- 7 to -8%; p < 0.05). Tult in the proximal tibia decreased in everyone, but the loss was attenuated in the rowing + ZA group. People with initially stronger bone tended to lose more strength. CONCLUSION: Overall, we observed increases in bone strength at the distal femur but not the proximal tibia, with FES-assisted rowing combined with ZA treatment. Rowing alone did not significantly prevent bone loss at either site, which might be attributed to insufficient mechanical loading.

Combination Therapy With Zoledronic Acid and FES-Row Training Mitigates Bone Loss in Paralyzed Legs: Results of a Randomized Comparative Clinical Trial.

Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation- (FES-) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES-rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES-rowing alone with FES-rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV (p = 0.05 to 0.006), the CTI (p = 0.009), and the BR (p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing-only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia (p = 0.05). A subgroup analysis of the rowing-only arm showed that gains in the CSI at the tibial metaphysis varied in a dose-dependent fashion based on the total amount of exercise performed (p = 0.009). These findings demonstrate that the osteogenic response to FES-rowing is dose-dependent. Combination therapy with ZA and FES-row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Anthropometric and biomechanical characteristics of body segments in persons with spinal cord injury.

People with spinal cord injury (SCI) experience bone and muscle loss in their paralyzed limbs that is most rapid and severe in the first 3years after injury. Restoration of mechanical loading through therapeutic physical activity may potentially slow or reverse post-SCI bone loss, however, therapeutic targets cannot be developed without accurate biomechanical models. Obesity is prevalent among SCI population, and it alters body composition and further affects parameters of these models. Here, clinical whole body dual-energy X-ray absorptiometry data from people with acute (n=39) and chronic (n=61) SCI were analyzed to obtain anthropometric parameters including segment masses, center of mass location, and radius of gyration for both obese and non-obese individuals. Chronic SCI was associated with higher normalized trunk mass of 3.2%BW and smaller normalized leg mass of 1.8%BW in males, but no significant changes in segment centers of mass or radius of gyration. People with chronic SCI had 58.6% lean mass in the trunk, compared to 66.6% lean mass in those with acute SCI (p=0.01), with significant changes in all segments. Obesity was associated with an increase in trunk mass proportion of 3.1%BW, proximal shifts in thigh and upper arm center of mass, and changes to thigh and shank radius of gyration. The data presented here can be used to accurately represent the anthropometrics of SCI population in biomechanical studies, considering obesity and injury duration.

Dual energy X-ray absorptiometry of the knee in spinal cord injury: methodology and correlation with quantitative computed tomography.

STUDY DESIGN: Comparison of diagnostic tests; methodological validation. OBJECTIVES: Primary: to investigate the precision and reliability of a knee bone mineral density (BMD) assessment protocol that uses an existing dual energy X-ray absorptiometry (DXA) forearm acquisition algorithm in individuals with spinal cord injury (SCI). Secondary: to correlate DXA-based knee areal BMD with volumetric BMD assessments derived from quantitative computed tomography (QCT). SETTING: Academic medical center, Chicago, IL, USA. PARTICIPANTS: a convenience sample of 12 individuals with acute SCI recruited for an observational study of bone loss and 34 individuals with chronic SCI who were screened for a longitudinal study evaluating interventions to increase BMD. MAIN OUTCOME MEASURES: Root-mean-square standard deviation (RMS-SD) and intra/inter-rater reliability of areal BMD acquired at three knee regions using an existing DXA forearm acquisition algorithm; correlation of DXA-based areal BMD with QCT-derived volumetric BMD. RESULTS: The RMS-SD of areal BMD at the distal femoral epiphysis, distal femoral metaphysis and proximal tibial epiphysis averaged 0.021, 0.012 and 0.016 g cm(-2), respectively, in acute SCI and 0.018, 0.02 and 0.016 g cm(-2) in chronic SCI. All estimates of intra/inter-rater reliability exceeded 97% and DXA-based areal BMD was significantly correlated with QCT-derived volumetric BMD at all knee regions analyzed. CONCLUSIONS: Existing DXA forearm acquisition algorithms are sufficiently precise and reliable for short-term assessments of knee BMD in individuals with SCI. Future work is necessary to quantify the reliability of this approach in longitudinal investigations and to determine its ability to predict fractures and recovery potential. SPONSORSHIP: This work was funded by the Department of Defense, grant number DOD W81XWH-10-1-0951, with partial support from Merck & Co, Inc.

Bone mineral and stiffness loss at the distal femur and proximal tibia in acute spinal cord injury.

SUMMARY: Computed tomography and finite element modeling were used to assess bone mineral and stiffness loss at the knee following acute spinal cord injury (SCI). Marked bone mineral loss was observed from a combination of trabecular and endocortical resorption. Reductions in stiffness were 2-fold greater than reductions in integral bone mineral. INTRODUCTION: SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. The large majority of these fractures occur around regions of the knee. Our purpose was to quantify changes to bone mineral, geometry, strength indices, and stiffness at the distal femur and proximal tibia in acute SCI. METHODS: Quantitative computed tomography (QCT) and patient-specific finite element analysis were performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range 2.6-4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. Changes in bone volumes, cross-sectional areas, strength indices and stiffness were also determined. RESULTS: Bone mineral loss was similar in magnitude at the distal femur and proximal tibia. Reductions were most pronounced at epiphyseal regions, ranging from 3.0 % to 3.6 % per month for integral BMC (p < 0.001) and from 2.8 % to 3.4 % per month (p < 0.001) for integral vBMC. Trabecular BMC decreased by 3.1-4.4 %/month (p < 0.001) and trabecular vBMD by 2.7-4.7 %/month (p < 0.001). A 3.8-5.4 %/month reduction was observed for cortical BMC (p < 0.001); the reduction in cortical vBMD was noticeably lower (0.6-0.8 %/month; p ≤ 0.01). The cortical bone loss occurred primarily through endosteal resorption, and reductions in strength indices and stiffness were some 2-fold greater than reductions in integral bone mineral. CONCLUSIONS: These findings highlight the need for therapeutic interventions targeting both trabecular and endocortical bone mineral preservation in acute SCI.

Bone mineral loss at the proximal femur in acute spinal cord injury.

UNLABELLED: This study used quantitative computed tomography to assess changes in bone mineral at the proximal femur after acute spinal cord injury (SCI). Individuals with acute SCI experienced a marked loss of bone mineral from a combination of trabecular and endocortical resorption. Targeted therapeutic interventions are thus warranted in this population. INTRODUCTION: SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. Some 10 to 20% of these fractures occur at the proximal femur. The purpose of this study was to quantify changes to bone mineral, geometry, and measures of strength at the proximal femur in acute SCI. METHODS: Quantitative computed tomography analysis was performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range, 2.6-4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at the femoral neck, trochanteric, and total proximal femur regions. Changes in bone volumes, cross-sectional areas, and surrogate measures of compressive and bending strength were also determined. RESULTS: During the acute period of SCI, subjects experienced a 2.7-3.3%/month reduction in integral BMC (p < 0.001) and a 2.5-3.1 %/month reduction in integral vBMD (p < 0.001). Trabecular BMC decreased by 3.1-4.7 %/month (p < 0.001) and trabecular vBMD by 2.8-4.4 %/month (p < 0.001). A 3.9-4.0 %/month reduction was observed for cortical BMC (p < 0.001), while the reduction in cortical vBMD was noticeably lower (0.8-1.0 %/month; p ≤ 0.01). Changes in bone volume and cross-sectional area suggested that cortical bone loss occurred primarily through endosteal resorption. Declines in bone mineral were associated with a 4.9-5.9 %/month reduction in surrogate measures of strength. CONCLUSIONS: These data highlight the need for therapeutic interventions in this population that target both trabecular and endocortical bone mineral preservation.