Muscle Density and Bone Quality of the Distal Lower Extremity Among Individuals with Chronic Spinal Cord Injury

Background:

Understanding the related fates of muscle density and bone quality after chronic spinal cord injury (SCI) is an important initial step in determining endocrine-metabolic risk.

Objective:

To examine the associations between muscle density and indices of bone quality at the distal lower extremity of adults with chronic SCI.

Methods:

A secondary data analysis was conducted in 70 adults with chronic SCI (C2-T12; American Spinal Injury Association Impairment Scale AIS] A-D; ≥2 years post injury). Muscle density and cross-sectional area (CSA) and bone quality indices (trabecular bone mineral density TbBMD] at the distal tibia 4% site] and cortical thickness CtTh], cortical area CtAr], cortical BMD CtBMD], and polar moment of inertia PMI] at the tibial shaft 66% site]) were measured using peripheral quantitative computed tomography. Calf lower extremity motor score (cLEMS) was used as a clinical measure of muscle function. Multivariable linear regression analyses were performed to determine the strength of the muscle-bone associations after adjusting for confounding variables (sex, impairment severity AIS A/B vs AIS C/D], duration of injury, and wheelchair use).

Results:

Muscle density was positively associated with TbBMD (b = 0.85 0.04, 1.66]), CtTh (b = 0.02 0.001, 0.034]), and CtBMD (b = 1.70 0.71, 2.69]) (P < .05). Muscle CSA was most strongly associated with CtAr (b = 2.50 0.12, 4.88]) and PMI (b = 731.8 161.7, 1301.9]) (P < .05), whereas cLEMS was most strongly associated with TbBMD (b = 7.69 4.63, 10.76]) (P < .001).

Conclusion:

Muscle density and function were most strongly associated with TbBMD at the distal tibia in adults with chronic SCI, whereas muscle size was most strongly associated with bone size and geometry at the tibial shaft.Key words: bone mineral density, bone quality, muscle density, muscle size, osteoporosis, peripheral quantitative computed tomography, spinal cord injurySpinal cord injury (SCI) is associated with sublesional muscle atrophy,^1–3 changes in muscle fiber type,^4,5 reductions in hip and knee region bone mineral density (BMD),^6–8 and increased central and regional adiposity after injury.^9,10 Adverse changes in muscle and bone health in individuals with SCI contribute to an increased risk of osteoporosis,^11–13 fragility fractures,¹⁴ and endocrine-metabolic disease (eg, diabetes, dyslipidemia, heart disease).^15–17 Crosssectional studies have shown a higher prevalence of lower extremity fragility fractures among individuals with SCI ranging from 1% to 34%.^18–20 Fragility fractures are associated with negative health and functional outcomes, including an increased risk of morbidity and hospitalization,^21,22 mobility limitations,²³ and a reduced quality of life.²⁴ Notably, individuals with SCI have a normal life expectancy, yet fracture rates increase annually from 1% per year in the first year to 4.6% per year in individuals greater than 20 years post injury.^25,26Muscle and bone are thought to function as a muscle-bone unit, wherein muscle contractions impose loading forces on bone that produce changes in bone geometry and structure.^27,28 A growing body of evidence has shown that individuals with SCI (predominantly those with motor complete injury) exhibit similar patterns of decline in muscle cross-sectional area (CSA) and BMD in the acute and subacute stages following injury.^4,11,29 Prospective studies have exhibited a decrease in BMD of 1.1% to 47% per year^6,7,30 and up to 73% in the 2 to 7 years following SCI.^8,14,31,32 Decreases in muscle CSA have been well-documented following SCI, with greater disuse atrophy observed after complete SCI versus incomplete SCI, presumably due to the absence of voluntary muscle contractions and associated mobility limitations.^1,2,16 Muscle quality is also compromised early after SCI, resulting in sublesional accumulation of adipose tissue in the chronic stage of injury^3,33,34; the exact time course of this event has been poorly elucidated to date. Adipose tissue deposition within and between skeletal muscle is linked to an increase in noncontractile muscle tissue and a reduction in muscle force-generating capacity on bone.^35,36 Skeletal muscle fat infiltration is up to 4 times more likely to occur in individuals with SCI,^1,16,37 contributing to metabolic complications (eg, glucose intolerance),¹⁶ reduced muscle strength and function,³⁸ and mobility limitations³ – all factors that may be associated with a deterioration in bone quality after SCI.The association between lean tissue mass and bone size (eg, BMD and bone mineral content) in individuals with SCI has been wellestablished using dual energy x-ray absorptiometry (DXA).^9,10,29,34 However, DXA is unable to measure true volumetric BMD (vBMD), bone geometry, and bone structure. Peripheral quantitative computed tomography (pQCT) is an imaging technique that improves our capacity to measure indices of bone quality and muscle density and CSA at fracture-prone sites (eg, tibia).^3,39 Recent evidence from cross-sectional pQCT studies has shown that muscle CSA and calf lower extremity motor score (cLEMS) were associated with indices of bone quality at the tibia in individuals with SCI.^13,40 However, neither study measured muscle density (a surrogate of fatty infiltration when evaluating the functional muscle-bone unit). Fatty infiltration of muscle is common after SCI^1,16,37 and may affect muscle function or the muscle-bone unit, but the association between muscle density and bone quality indices at the tibia in individuals with chronic SCI is unclear. Muscle density measured using pQCT may be an acceptable surrogate of muscle quality when it is difficult to assess muscle strength due to paralysis.^3,39 Additionally, investigating which muscle outcome (muscle density, CSA, cLEMS) is most strongly associated with vBMD and bone structure may inform modifiable targets for improving bone quality and reducing fracture risk after chronic SCI.The primary objective of this secondary analysis was to examine the associations between pQCTderived calf muscle density and trabecular vBMD at the tibia among adults with chronic SCI. The secondary objective was to examine the associations between calf muscle density, CSA, and function and tibial vBMD, cortical CSA and thickness, and polar moment of inertia (PMI). First, we hypothesize that calf muscle density will be a positive correlate of trabecular and cortical vBMD, cortical CSA and thickness, and PMI at the tibia in individuals with chronic SCI. Second, we hypothesize that of the key muscle variables (cLEMS, CSA and density), calf muscle density and cLEMS will be most strongly associated with trabecular vBMD, whereas calf muscle CSA will be most strongly associated with cortical CSA and PMI.