Current and emerging therapies for osteoporosis

Abstract

Bone remodeling is a dynamic process in which activated osteoclasts resorb bone and osteoblasts generate a bone matrix that undergoes mineralization. This process repairs microdamage' the microscopic cracks that develop in bone during regular activity-and ensures skeletal strength. A number of local and systemic factors mediate bone cell activity. Systemic regulators include endogenous parathyroid hormone (PTH), vitamin D metabolites, prostaglandins, cortisol, and sex hormones. A number of cytokines and growth factors regulate bone cell function at the local level. For example, bone resorption and formation are tightly orchestrated via the RANK/receptor activator of NF-kappa B ligand (RANKL)/osteoprotegerin (OPG) system. Estrogen deficiency, glucocorticoid use, and immune-mediated conditions lead to an imbalance in the RANKL-OPG ratio, inducing osteoclastogenesis and accelerated bone resorption. A number of steps in the tightly orchestrated bone remodeling process can be targeted with pharmacotherapy. This article reviews the available and emerging treatments that inhibit resorption (the antiresorptive or anticatabolic agents) or augment bone formation (anabolic therapy).