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Changes in Serum Receptor Activator of Nuclear Factor-B Ligand, Osteoprotegerin, and Interleukin-6 Levels in Patients with Glucocorticoid-Induced Osteoporosis Treated with Human Parathyroid Hormone (1–34)

Department of Medicine, University of California at San Francisco, San Francisco, California 94143

Address all correspondence and requests for reprints to: Dr. Nancy Lane, Division of Rheumatology, Box 0868, University of California at San Francisco, San Francisco, California 94143. E-mail: nelane{at}itsa.ucsf.edu.

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-B 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) (40 µg) 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.

This work was supported by National Institutes of Health Grants AR048841-01 and DK46661-07, the Rosalind Russell Arthritis Research Center, and by a Research Enhancement Award from the Department of Veterans Affairs.

Abbreviations: BSAP, Bone-specific alkaline phosphatase; DPD, deoxypyridinoline cross-links; GIOP, glucocorticoid-induced osteoporosis; hPTH, human PTH; HRT, hormone replacement therapy; IL-6sR, IL-6 soluble receptor; OC, osteocalcin; OPG, osteoprotegrin; RANK, receptor activator of nuclear factor-B; RANKL, RANK ligand; sRANKL, soluble RANKL.

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