[Clinical implications of new insights into the regulation of bone resorption].
It has recently been discovered that the receptor activator of nuclear kappaB-ligand (RANKL) plays a key role in the activation, differentiation and proliferation ofosteoblasts. The effects of RANKL are counteracted by the decoy receptor osteoprotegerin (OPG), which protects against bone resorption by preventing RANKL from coupling to its receptor RANK. An increase in the balance between RANKL and OPG leads to increased bone resorption (both locally and generalised), e.g. in patients with postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, multiple myeloma, other malignancies with skeletal metastases, or rheumatoid arthritis. The development of new anti-osteoporotic drugs, based on the restoration of the imbalance between RANKL and OPG, may be a breakthrough in optimising the treatment of patients with bone diseases. However, the results of studies on fracture reduction, the safety profile, the costs of the new drugs and their comparison with bisphosphonates, currently the gold standard in osteoporosis treatment, must be awaited.
Lems
W F
WF
VU Medisch Centrum, afd. Reumatologie, 4A42, Postbus 7057, 1007 MB, Amsterdam. wf.lems@vumc.ml
Bijlsma
J W J
JW
D001847:Bone Diseases / Q000188:drug therapy / Q000378:metabolism*; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D063065:Organophosphonates / Q000627:therapeutic use; D010006:Osteoblasts / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D063065:Organophosphonates; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human