Preface [Hot Topic:Anabolic Agents for the Treatment of Osteoporosis (Executive Editor: Naohisa Miyakoshi)]

摘要

Osteoporosis is a growing worldwide public health problem that is characterized by compromised resistance of bone against mechanical loads, as a consequence of reduced bone mass and changes in microarchitecture. Skeletal fractures are the clinical manifestation of the disease, with older female patients the most severely affected. Osteoporosis develops through an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts resulting in increased bone loss.nnNumerous agents currently used for the treatment of osteoporosis are antiresorptive in mechanism, acting primarily to inhibit osteoclast-mediated bone loss. These include bisphosphonates, calcitonins, estrogen and selective estrogen receptor modulators. These antiresorptive agents may be associated with an increase in bone density in an indirect manner by reducing the remodeling space and by prolonging the duration of mineralization. However, to enhance bone mass in patients with decreased bone formation, treatment with drugs that exert anabolic effects by increasing bone formation appear most desirable. Particularly, for patients who have severe osteoporosis at high risk for fractures, there is a need to develop agents that reverse osteoporosis by stimulating bone formation.nnThis issue of “Current Pharmaceutical Design” contains the text of seven invited review articles regarding bone anabolic agents for the treatment of osteoporosis. The concept of anabolic agents is based on a physiologic process entirely different from inhibition of bone resorption, namely direct stimulation of bone formation.nnThe first two articles discuss vitamins that have anabolic effects on bone. Dr. van Driel et al. [1] review effects of vitamin D, a classic calcium regulator, and its metabolites on osteoblast differentiation and control. The review by Dr. Iwamoto et al . [2] suggests that vitamin K2, a cofactor of γ-carboxylase that converts the glutamic acid residue to a γ-carboxyglutamic acid residue in osteocalcin molecules, exerts anabolic effects on bone in vitro and in vivo. There is evidence from human intervention studies that vitamins D and K2 affect bone density.nnThe next two articles discuss bone growth factors for possible use in the therapy of osteoporosis. Dr. Kasukawa et al. [3] review potential roles of growth hormone and insulin-like growth factors in musculoskeletal tissues, especially their effects on bone formation. Dr. Fromigué et al. [4] summarize the evidence indicating that transforming growth factor-ß and fibroblast growth factors are important factors that promote osteoprogenitor cell proliferation and osteogenesis.nnThe potential use of statins, also known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, for the treatment of osteoporosis is reviewed by Dr. Koida et al. [5] Statins can increase bone formation and bone mass in animals and humans. A review on parathyroid hormone (PTH), authored by myself (Dr. Miyakoshi) [6], puts particular focus on its effect on cancellous bone architecture and recent clinical trials. At present, in practical use, PTH seemed to be the most promising bone anabolic agent for the treatment of osteoporosis.nnIn addition to these articles reviewing therapeutic agents, the importance of mechanical loading as an anabolic stimulus for bone is highlighted by the contribution of Drs. Turner and Robling [7]. Bone cells are capable of sensing and responding to mechanical forces. The mechanisms for bone formation by mechanical loading involve a multistep process of cellular mechanotransduction.nnAll the authors in this issue are experts in their fields. I am confident that this special issue will serve as an important source of information for researchers. I wish to convey my sincere gratitude to all the eminent authors who contributed to this special issue with their hard work and dedication.