The results of simple biomechanical unloading in models of acute-disuse osteoporosis are influenced by systemic and regional effects of the method used to generate the bone loss. A model in which strain-gauge measurements confirmed that the os calcis was unloaded in healthy ewes during ambulation was assessed by histomorphometry. Twelve nonovariectomized adult female Welsh mountain sheep were submitted to hock joint immobilization by an external fixation procedure from the tibia to the metatarsus for a period of 12 wk. Histomorphometric analysis showed that this model was able to produce pure local bone loss, as transiliac bone biopsies failed to reveal any difference between the initial and final results. Immobilized and nonimmobilized calcanei were both removed postmortem. After the 12 wk of the study, osteoclastic activity was increased in accordance with the usual disuse process. An unexpected increase of osteoblastic activity was also observed, possibly related to recovery after the initial dramatic bone loss, but an artifact of the surgical procedure such as a regional acceleration phenomenon cannot be definitively excluded. However, the increased osteoblastic activity was not sufficient to prevent accentuation of the negative bone balance, resulting in a 29% decrease of trabecular bone volume in immobilized calcanei compared with nonimmobilized calcanei. This reduction was due to thinning of trabeculae (72.4 +/- 12.1 vs. 98.9 +/- 15.9 microns; P < 0.05) without any change in trabecular number (2.74 +/- 0.72 vs. 2.79 +/- 0.40/mm2; not significant). In conclusion, this model only locally increased both osteoclastic and osteoblastic activities leading to bone loss and architectural modifications. The decreased bone formation usually observed in other models of disuse osteoporosis may therefore not constitute a local phenomenon generated by unloading.
Role of endoplasmic reticulum stress in disuse osteoporosis
