Developments in the scientific understanding of osteoporosis

Abstract

During the past 10 years we have experienced very significant developments in our understanding of bone biology, and this has improved our abilities to both diagnose and treat patients with osteoporosis. This review covers some of the significant discoveries in bone biology that have led to a better understanding of osteoporosis, including a few of the discoveries that have been translated into new therapies to treat patients with osteoporosis and the structural deterioration of patients with inflammatory arthritis.

Figure 1

Pathways for osteogenesis and osteoclastogenesis. Osteoblasts mature from mesenchymal stem cells to preosteoblasts. The Wnt signaling pathway antagonists (DKK-1, sclerostin, and SFRP1) and serotonin all inhibit osteogenesis. A number of cell types can synthesize Wnt signaling antagonists. Fibroblast-like synoviocytes from rheumatoid arthritis patients after stimulation with TNF-α, and myeloma cells synthesize DKK-1 and osteocytes synthesize sclerostin. Osteoblasts also now are known to be the main controllers of osteoclastogenesis through the production of RANKL by pre-osteoblast cells. The antagonist of RANKL, OPG, is produced by mature osteoblasts and prevents RANKL from binding to its receptor, RANK, so that osteoclast maturation and activity are inhibited. DKK, dickkopf; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor-κB ligand; SFRP, secreted frizzled-related protein; TNF, tumor necrosis factor.