title: Changes in serum receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34).
abstract: Changes in biochemical markers of bone turnover following intermittent injections of human (h)PTH (1-34) suggest that bone formation is initially favored over bone resorption. hPTH (1-34) is also known to influence osteoclast maturation and activity through modulation of osteoblast-derived cytokines, such as receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), IL-6, and IL-6 soluble receptor (IL-6sR). In this experiment, we investigated the changes in serum levels of soluble RANKL (sRANKL), OPG, IL-6, and IL-6sR in patients with glucocorticoid-induced osteoporosis treated with hPTH (1-34). Fifty-one postmenopausal women with glucocorticoid-induced osteoporosis were randomized to receive 12 months of 400 U hPTH (1-34) ( approximately 40 microg) daily and standard hormone replacement therapy, or hormone replacement therapy alone. Serum levels of sRANKL, OPG, IL-6, and IL-6sR were measured at baseline, 1 month, and every 3 months thereafter for a total of 24 months. hPTH (1-34) caused a rapid and significant increase in sRANKL within 1 month, and the levels remained elevated throughout the duration of therapy. IL-6 and IL-6sR increased significantly within 1 month, but returned to baseline levels more rapidly. In contrast, OPG was mildly suppressed beginning 6 months after hPTH therapy. These data support the hypothesis that hPTH (1-34) initially stimulates osteoblast maturation and function, which in turn leads to osteoclast activation and a gradual rebalancing of bone formation and resorption.
authors.affiliation: Division of Rheumatology, Box 0868, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Buxton
authors.forename: Wei
authors.initials: W
authors.lastname: Yao
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lane
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000009:adverse effects*; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008562:Membrane Glycoproteins / Q000097:blood* / Q000737:chemistry; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000097:blood*; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000737:chemistry; D018124:Receptors, Tumor Necrosis Factor; D012995:Solubility; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human