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

Abstract

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. (J Bone Miner Res 1999;14:518-527)

Plasma levels of receptor activator of nuclear factor‐κB ligand and osteoprotegerin in patients with neuroblastoma

“…26 In our hands, the amount of circulating OPG resulted much higher than that reported by others, but it was consistent with the values obtained by using antibodies able to detect both monomeric and homodimeric forms of OPG. 28,29 OPG was significantly lower in neuroblastoma patients than in the healthy children, but no differences were found according to either the stage of disease or the presence of metastasis. The ROC curve analysis showed that all patients had abnormal values, suggesting that OPG measuring could be a useful tool for the differential diagnosis of small round-cell tumors in pediatric age, as well as for the identification of neuroblastoma with unusual presentation.…”

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

“…In our study, breast cancer patients with or without bone metastases had increased OPG levels compared to healthy controls, contrasting with the absence of elevation found by Lipton et al (2002). The reasons for these discrepancies are unclear, but they could be attributed to patient population characteristics and/or specificity of assays for the various circulating forms of OPG (Yano et al, 1999).…”

Association between Increased Serum Osteoprotegerin Levels and Improvement in Bone Mineral Density after Parathyroidectomy in Hemodialysis Patients

“…Since OPG suppresses bone resorption and increased alkaline phosphatase (Alk-P) activity is associated with bone formation, both of these markers may be elevated during bone anabolism. High serum levels of Alk-P and OPG were reported in a study of high turnover bone disease (Yano et al 1999). However, the nature of the relationship between serum OPG and bone turnover markers following PTX is still debated.…”