Contribution of muscular weakness to osteoporosis: computational and animal models.

摘要

BACKGROUND: Chronic weakness of the femoral musculature with old age may result in prolonged exposure of bone to critical understressing and, thus, cause osteoporotic changes. This study aims at quantifying long-term changes in thickness and mechanical properties of trabecular bone at the proximal femur due to muscular weakness. METHODS: We utilized computational models of typical planar trabecular lattices at the proximal femur for simulating long-term changes in morphological and mechanical properties of trabecular bone. Incorporating cellular communication network with osteocytes as mechanosensors, the models were able to mimic mechanotransduction and consequent thickening and/or thinning of individual trabeculae in response to altered gluteus muscle and hip joint loads. We also studied a rat model (n=14) in which we surgically detached the gluteus muscle, to approximately 50% or completely. FINDINGS: The computational simulations showed that when the force of the gluteus decreased (with or without simultaneous decrease in hip joint load), the most dramatic degradation in bone density, strength and stiffness occurred at the greater trochanter. Animal studies also demonstrated significant thinning of femoral trabeculae after 19 weeks of adaptation. Specifically, Tukey-Kramer analysis showed that rats subjected to partial surgical detachment of the gluteus had femoral trabeculae that were 22% thinner than controls (P<0.05). INTERPRETATION: The present study showed that in both the computer and animal models, manipulation of muscle loading produced a significant stimulus for bone to adapt, i.e., a stimulus that is beyond its irresponsive 'lazy zone'. Accordingly, the results obtained herein indicate that muscular weakness may be an important factor contributing to osteoporosis.