Heterogeneity in microstructural deterioration following spinal cord injury

Background: Modelling and remodelling adapt bone morphology to accommodate strains commonly encountered during loading. If strains exceed a threshold threatening fracture, modelling-based bone formation increases bone volume reducing these strains. If unloading reduces strains below a threshold that inhibits resorption, increased remodelling-based bone resorption reduces bone volume restoring strains, but at the price of compromised bone volume and microstructure. As weight-bearing regions are adapted to greater strains, we hypothesized that microstructural deterioration will be more severe than at regions commonly adapted to low strains following spinal cord injury. Methods: We quantified distal tibial, fibula and radius volumetric bone mineral density (vBMD) using high-resolution peripheral quantitative computed tomography in 31 men, mean age 43.5 years (range 23.5-75.0), 12 with tetraplegia and 19 with paraplegia of 0.7 to 18.6 years duration, and 102 healthy ageand sex-matched controls. Differences in morphology relative to controls were expressed as standardized deviation (SD) scores (mean SD). Standardized between-region differences in vBMD were expressed as SDs (95% confidence intervals, CI). Results: Relative to controls, men with tetraplegia had deficits in total vBMD of-1.72 +/- 1.38 SD at the distal tibia (p < 0.001) and 0.68 +/- 0.69 SD at distal fibula (p = 0.041), but not at the distal radius, despite paralysis. Deficits in men with paraplegia were-2.14 +/- 1.50 SD (p < 0.001) at the distal tibia and-0.83 +/- 0.98 SD (p = 0.005) at the distal fibula while distal radial total vBMD was 0.23 +/- 1.02 (p = 0.371), not significantly increased, despite upper limb mobility. Comparing regions, in men with tetraplegia, distal tibial total vBMD was 1.04 SD (95%CI 0.07, 2.01) lower than at the distal fibula (p = 0.037) and 1.51 SD (95%CI 0.45, 2.57) lower than at the distal radius (p = 0.007); the latter two sites did not differ from each other. Results were similar in men with paraplegia, but total vBMD at the distal fibula was 1.06 SD (95%CI 0.35, 1.77) lower than at the distal radius (p = 0.004). Conclusion: Microarchitectural deterioration following spinal cord injury is heterogeneous, perhaps partly because strain thresholds regulating the cellular activity of mechano-transduction are region specific.