Prostaglandins and Bone Metabolism

Publisher Summary This chapter focuses on the effects of prostaglandins (PG) and other eicosanoids on bone resorption and formation. Eicosanoids are oxygenated 20-carbon fatty acids derived from polyunsaturated eicosatrienoic, eicosatetranoic (arachidonic), and eicosapentanoic fatty acids. The production of PGs involves three major steps which include hormone-or stress-activated mobilization of AA, conversion of AA to prostaglandin endoperoxide H 2 (PGH 2 ), and conversion of diffusible PGH 2 by tissue-specific isomerases and reductases to PGE 2 , PGD 2 , PGF 2α , prostacyclin (PGI 2 ), and thromboxane. The committed step in the conversion of AA to PGs is catalyzed by a bifunctional enzyme, which converts free AA to PGG 2 in a cyclooxgenase reaction followed by reduction of PGG 2 to PGH 2 in a peroxidase reaction. This enzyme, formally named prostaglandin endoperoxide H synthase or prostaglandin G/H synthase (PGHS), is popularly called cyclooxgygenase (COX) in reference to its first function. The individual PG synthases are differentially distributed in tissues and are believed to influence PG production largely by determining the predominant type of prostanoid synthesized in a particular tissue. PGE 1 and PGE 2 stimulate osteoclast formation in marrow cultures. The PG enhancement of stimulated osteoclast formation in marrow culture may reflect the increased formation of new osteoclastic precursors, while stimulated resorption in organ culture may be more dependent on activation of a pool of available osteoclastic precursors. When added to isolated osteoclasts in vitro, PGE 2 transiently inhibits bone resorption. PGs can have both stimulatory and inhibitory effects on bone formation. PGs can increase both periosteal and endosteal bone formation in the rat and produce substantial increases in bone mass, similar to the effects of PTH. At high concentrations, PGs can inhibit collagen synthesis in cell and organ culture. This inhibitory effect occurs largely via transcriptional inhibition of collagen and are mediated by the FP receptor rather than an EP receptor.