Principal Investigator: Dennis R. Carter, PhD Project Staff: Gary S. Beaupré, PhD; Robert Marcus, MD; and C.J. Hernandez, MS Project Category: Osteoporosis Osteoporosis is a disease characterized by bone loss, decreased bone strength and an increased risk of fracture. Bone loss with osteoporosis occurs as a result of an imbalance in the bone remodeling process that is associated with aging in ways that are not yet fully understood. Bone remodeling normally involves an ordered sequence of events orchestrated by groups of osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells) referred to as basic multicellular units (BMUs). Factors such as hormones (estrogen, parathyroid hormone), anti-resorptive drugs (bisphosphonates, calcitonin) and nutritional supplements (calcium and vitamin D) are known to influence BMU activity. The specific objective of this pilot study is to develop a theoretical framework and computational model of bone remodeling at the BMU-level that will be used to predict changes in mineralized bone volume fraction, osteoid volume fraction, and percent bone mineralization in response to changes in metabolic stimuli. This new model for describing BMU activity is fully three-dimensional and utilizes clinical measurements of histomorphometric parameters along with an idealized representation of BMU geometry. Our preliminary investigations show that, of the ten required histomorphometric input parameters (all of which have been either measured or derived from histomorphometric analysis), three parameters are particularly influential in terms of the changes in bone mass that are seen during osteoporosis progression and treatment. Using the output from the BMU-based model we will calculate bone strength as a function of bone volume fraction and percent mineralization. We believe that volume fraction and mineralization will provide a better prediction of bone strength than is currently provided by bone apparent density alone. Publications:
Funding Source: VA RR&D Merit Review Funding Status: Funded |
