Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis

J Bone Miner Res. 1999 Apr;14(4):518-27. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Bone Density
  • Bone Diseases, Metabolic / blood
  • Bone Diseases, Metabolic / metabolism
  • Case-Control Studies
  • Dimerization
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycoproteins / blood*
  • Glycoproteins / chemistry
  • Glycoproteins / immunology
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Osteoporosis, Postmenopausal / blood*
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoprotegerin
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear*
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology


  • Antibodies, Monoclonal
  • Glycoproteins
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNFRSF11B protein, human
  • Tnfrsf11b protein, mouse