Adaptation of cancellous bone to aging and immobilization in the rat: A single photon absorptiometry and histomorphometry study

Abstract

Nine-month-old female rats were double-labeled with bone markers and subjected to right hindlimb immobilization or served as control for 0, 2, 10, 18, or 26 weeks. The right limb was immobilized against the abdomen, thus unloading it, while the left limb was overloaded during ambulation. Single photon absorptiometry and cancellous bone histomorphometry were performed on dissected intact femur and 20-microns-thick undecalcified specimens of the proximal tibial metaphysis. In the unloaded limb, immobilization-induced muscle and cancellous bone loss occurred rapidly before 10 weeks and stabilized at 50% less bone mass after 18 weeks. Unloading caused a negative bone balance from a combination of elevated bone resorption and depressed bone formation. At 2, 10, and 18 weeks of immobilization, the ratios of bone resorption to bone formation surfaces were 1.6, 1.5, and 1.3, respectively; at 26 weeks, the ratio was 1. The bone loss was accompanied by poorer trabecular architecture (trabecular number decreased and trabecular separation increased), reaching the maximum at 18 weeks and stabilizing thereafter. These observations are in general agreement with Frost's postulate for mechanical effects on lamellar bone remodeling, and the findings on disuse osteoporosis in man. Therefore, the one-legged immobilization model can be useful in studies of the mechanisms of structural adaptation to mechanical usage.

A multiscale analytical approach for bone remodeling simulations: Linking scales from collagen to trabeculae

“…Looking at the dynamic response of the analytical bone remodeling system, the model is found temporally stable and consistent with experimental observations of bone density changes during disuse and aging [44,45]. However, in the analytical simulations of Figs.…”

Histomorphometric and Densitometric Changes in the Femora of Spinal Cord Transected Mice

“…Researchers have shown a 10-30% decrease in femoral cancellous tissue within a few weeks (up to 50% after 18 weeks) of unilateral hindlimb immobilization using an elastic band in 6-to 9-month-old female rats (Li et al, 1990;Maeda et al, 1993). Similar levels but faster bone losses (within 2-8 weeks of immobilization) have been detected with a comparable model of disuse but in younger rats (2-3 months old, Chen et al, 1992).…”

“…In animal models of disuse, traditionally in rats, hindlimb immobilization has been found to induce a drastic and sudden loss of femoral bone tissue, suggesting that dif-ferent mechanisms may be involved in disuse-related (fast bone loss) vs. age-related osteoporosis (slow bone loss; Bagi and Miller, 1994). For instance, a 10-30% (up to 50% after 18 months) decrease of cancellous bone was found within a few weeks in the ipsilateral femur of rats that had their hindlimbs immobilized with a cast or an elastic bandage (Li et al, 1990;Chen et al, 1992;Maeda et al, 1993). Some of the changes associated with disuse are believed to be mediated by both an increase of osteoclastic bone resorption and a decrease of osteoblastic bone formation (Rantakokko et al, 1999;Kingery et al, 2003).…”

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…The first determinant depends on the availability of an animal model that mimics a human disease involving bone repair so that the data generated can be used to predict the drug efficacy and safety in patients. Examples of animal models with good predictability of clinical outcomes include models of postmenopausal osteoporosis [87][88][89][90][91][92], models of glucocorticoid induced bone loss [93][94][95][96], models of cancer metastasis to bone [97], disuse models [98,99], fracture healing models [100][101][102][103] and several others. The second determinant of successful experimentation relates to translational biomarkers of novel therapy efficacy and safety that can be accurately predicted and monitored in patients.…”