The Effects of Bisphosphonates on Bone Remodeling: Analysis of Microdamage Targeting by BMUs, BMU Velocity and Crack Surface Density

Abstract

The Effects of Bisphosphonates on Bone Remodeling: Analysis of Microdamage Targeting by BMUs, BMU Velocity and Crack Surface Density By Daniel Wayne Hale Studies have indicated that microdamage in the bone matrix both activates and steers BMUs (Basic Multicellular Units, the groups of osteoclasts and osteoblasts that resorb and form bone respectively) toward the damage in order to replace damaged bone with new, mechanically sound bone. Also, bisphosphonate drugs have been shown to greatly suppress the remodeling process and, with such effects, are commonly used in the treatment of osteoporosis. It was hypothesized that BMUs do indeed target microdamage around them and tunnel away from the dominant lines of force in bone in order to remove the damage. Additionally it was believed that bisphosphonates would have a suppressive force on the BMU's ability to seek out and remove microdamage. This study explored a further hypothesis that bisphosphonates would decrease BMU velocity and osteonal area while increasing crack surface density in a dose-dependent manner. Thirty-six rib bone samples were obtained from the Indiana University School of Medicine from a three year canine study in which skeletally mature beagles were administered the bisphosphonate Alendronate in doses matching, on a body weight basis, those used to treat postmenopausal osteoporosis. Control, clinical dose (Alendronate 0.2 mg/kg body weight), and five times clinical dose (Alendronate 1.0 mglkg body weight) treatment groups were created with 12 dogs in each group. Before harvesting rib bones, the dogs were injected with calcein at two different time periods to mark areas of new bone formation. For this study, data for mean crack length, resorption space density, osteonal area, and crack surface density were obtained from