Pathogenesis of osteoporosis: concepts, conflicts, and prospects.
Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.
Raisz
Lawrence G
LG
University of Connecticut Health Center, Musculoskeletal Institute, Farmington, Connecticut 06032, USA. raisz@nso.uchc.edu
D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D050723:Fractures, Bone; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006728:Hormones / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015663:Osteoporosis, Postmenopausal / Q000473:pathology; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism
D004967:Estrogens; D006023:Glycoproteins; D006728:Hormones; D020738:Leptin; D008024:Ligands; D016328:NF-kappa B; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D011453:Prostaglandins; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; D014807:Vitamin D; D009569:Nitric Oxide; D003094:Collagen; D002118:Calcium