Immunological Characterization of Circulating Osteoprotegerin/Osteoclastogenesis Inhibitory Factor: Increased Serum Concentrations in Postmenopausal Women with Osteoporosis

• Published in: Journal of bone and mineral research Vol. 14; no. 4; pp. 518 - 527
• Main Authors: Yano, Kazuki, Tsuda, Eisuke, Washida, Naohiro, Kobayashi, Fumie, Goto, Masaaki, Harada, Atsushi, Ikeda, Kyoji, Higashio, Kanji, Yamada, Yoshiji
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.04.1999; American Society for Bone and Mineral Research
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Antibody Specificity; Biological and medical sciences; Bone Density; Bone Diseases, Metabolic - blood; Bone Diseases, Metabolic - metabolism; Case-Control Studies; Dimerization; Diseases of the osteoarticular system; Enzyme-Linked Immunosorbent Assay; Female; Glycoproteins - blood; Glycoproteins - chemistry; Glycoproteins - immunology; Humans; Male; Medical sciences; Mice; Middle Aged; Osteoporosis, Postmenopausal - blood; Osteoporosis, Postmenopausal - metabolism; Osteoporosis. Osteomalacia. Paget disease; Osteoprotegerin; Protein Conformation; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Proteins - chemistry; Recombinant Proteins - immunology; Human; Senescence; Pathogenesis; Diseases of the osteoarticular system; Cytokine; Bone disease; Osteoclast; Bone remodeling; Blood plasma; Osteoarticular system; Osteoporosis; Postmenopause; Female; Bone; Inhibition; Differentiation; Quantitative analysis
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.1999.14.4.518

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family of proteins and plays an important role in the negative regulation of osteoclastic bone resorption. Whether OPG/OCIF circulates in human blood and how its level changes under pathological conditions is not known. To address these issues, a panel of monoclonal antibodies was generated against recombinant OPG/OCIF and screened for reactivity with solid‐phase monomeric and homodimeric forms of the recombinant protein. Antibodies that showed high affinity for both forms of OPG/OCIF and those that selectively recognized the homodimer were identified, enabling development of two types of sensitive enzyme‐linked immunosorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and one specific for the homodimer. Characterization of circulating OPG/OCIF with these ELISAs revealed that the protein exists in human serum mainly in the monomeric form. The serum concentration of OPG/OCIF increased with age in both healthy Japanese men and women, and was significantly higher in postmenopausal women with osteoporosis than in age‐matched controls. Within the osteoporotic group, serum OPG/OCIF concentrations were higher in patients with low bone mass. Serum OPG/OCIF concentrations were also significantly increased in those postmenopausal women with a high rate of bone turnover, as determined by increased serum bone‐specific alkaline phosphatase and urinary excretion of pyridinoline and deoxypyridinoline. The results suggested that circulating OPG/OCIF levels are regulated by an age‐related factor(s) and that the increased serum concentration may reflect a compensative response to enhanced osteoclastic bone resorption and the resultant bone loss rather than a cause of osteoporosis.