Ugeskr Læger 2002;164(27): 3526-30.
Summary Osteoclast function is regulated by neighbouring osteoblasts: osteoprotegerin, RANK, and RANK ligand constitute a unique regulatory system for bone resorption with important pathophysiological and therapeutic aspects. Ugeskr Læger 2002; 164: 3526-30. Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteoblasts. Most calci- tropic hormones act indirectly on osteoclasts through receptors on neighbouring osteoblasts. The discovery of osteoprotegerin (OPG), the receptor activator of nuclear factor-kb ligand (RANKL), and its receptor (RANK) has elucidated these phenomena. It appears that osteoclast differentiation, activity, and survival are regulated by the proportion of inhibiting OPG to stimulating RANKL. OPG and RANKL are produced by osteoblasts, whereas RANK is located to the osteoclasts. Treatment with OPG inhibits bone resorption in postmenopausal women. Mutations in the system may be responsible for focal skeletal disorders. The discovery opens up for new treatment opportunities in postmenopausal and steroid-induced osteoporosis, Paget's disease, hypercalcaemia, and rheumatoid arthritis.