Calcium homeostasis is governed by the interplay of intestinal calcium absorption, renal excretion and skeletal exchange of calcium. In the adult skeleton, bone formation and resorption are closely coupled. Supraphysiological levels of corticosteroids can interfere with calcium metabolism through various pathways, resulting in decreased bone formation and enhanced bone resorption, and thus leading to accelerated osteopenia. The resulting fractures typically occur at sites rich in trabecular bone, though cortical thinning is known to occur as well. Further, the architectural changes paralleling the reduction in mass density are different from those in involutional osteoporosis and there are indications that steroid-induced osteopenia compromises skeletal strength at higher mass density. The present project seeks to investigate the effects of corticosteroids on trabecular morphology and the biomechanical consequences of these architectural changes by means of magnetic resonance (MR) micro-imaging and dual-energy X-ray absorptiometry (DEXA) in vivo and in vitro in a rabbit model. The rabbit is particularly suited as model; in its mature skeleton remodeling prevails over modeling and significant bone loss occurs upon exposure to corticosteroids in comparatively short times. Most prior work has been done post mortem by means of densitometric and histomorphometric techniques. Using new ultrahigh-resolution magnetic resonance (MR) imaging and computer-based image analysis we propose to evaluate the steroid-induced skeletal changes serially in vivo. Specifically, we propose to test the following hypotheses: (1) The reduction in bone mass results in changes of the trabecular microstructure, which can be characterized quantitatively by in vivo 3D MR imaging and image processing. (2) The time course of the changes in trabecular bone mass and architecture, in response to administration of dexamethasone, can be evaluated by serial quantitative MRI measurements in vivo in a rabbit model. (3) Discontinuation of corticosteroid administration leads to partial re-establishment of skeletal integrity and mechanical competence. (4) Supplementation of corticosteroid treatment with gonadal steroids alleviates bone loss. (5) The corticosteroid-induced changes in trabecular microarchitecture are accompanied by a predictable reduction in the bone's elastic modulus.
| Takahashi, Masaya; Saha, Punam K; Wehrli, Felix W (2006) Skeletal effects of short-term exposure to dexamethasone and response to risedronate treatment studied in vivo in rabbits by magnetic resonance micro-imaging and spectroscopy. J Bone Miner Metab 24:467-75 |
