HO is an employee
of Ajinomoto Pharmaceuticals Company Limited. SH is an employee of Takeda Pharmaceutical Company Limited. TN has received consulting fees (Ajinomoto Pharmaceuticals, Asahi Kasei Pharma, Astellas, Banyu, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Ono, Takeda, and Teijin Pharma) and belongs to the Japan Ministry of Health, Welfare and Labour as a councilor learn more for hospital administration and social medical insurance. This study was supported by the Joint Development Program of Ajinomoto Pharmaceuticals Co., Ltd. and Takeda Pharmaceutical Company Limited. The authors thank David P. Figgitt, Content Ed Net, for providing editorial assistance in the preparation of this article; funding for editorial assistance was provided by Ajinomoto Co., Ltd. and Takeda Pharmaceutical Company Limited. “
“All genetic and environmental selleck chemicals llc factors influencing bone’s material and structural strength express their effects through the final common pathway of bone modeling and remodeling . During young adulthood, this cellular machinery maintains bone’s material composition and microstructure by replacing a volume of old or damaged bone with an equal volume of new bone; no permanent bone loss
or structural deterioration occurs  and . As age advances, and especially after menopause, remodeling becomes unbalanced and accelerated; large numbers of remodeling units, each depositing a smaller volume of bone than they remove, cause structural deterioration . Remodeling upon trabecular surfaces thins and disconnects trabeculae. Remodeling upon endocortical surfaces thins the cortex while intracortical remodeling upon the myriads of Haversian canals enlarges them focally, increasing porosity . Intense intracortical remodeling in the inner third of the cortex adjacent to the medullary canal produces large intracortical pores and cortical fragments that occupy a ‘transitional zone’ between the compact-appearing but increasingly
porous cortex and the trabecular compartment. To inhibit remodeling, antiresorptive agents must either prevent osteoclastogenesis or access existing remodeling sites and reduce resorptive Non-specific serine/threonine protein kinase activity or the longevity of osteoclasts already formed and resorbing bone . Antiresorptive efficacy also may depend on the accessibility of treatments to the site being remodeled. Trabeculae are thin plates in close contact with vascular spaces. These plates have a large surface area allowing the adsorption of bisphosphonates into trabecular bone matrix so that bisphosphonate is present in high concentration ,  and . When osteoclasts excavate and engulf trabecular bone matrix they are likely to also engulf bisphosphonate and inhibit remodeling . Inhibiting intracortical remodeling may be more challenging because cortical bone has less surface area per unit volume of mineralized bone matrix upon which bisphosphonates can be adsorbed.