Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: Increased serum concentrations in postmenopausal women with osteoporosis
K. Yano et al., Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: Increased serum concentrations in postmenopausal women with osteoporosis, J BONE MIN, 14(4), 1999, pp. 518-527
Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a solu
ble member of the tumor necrosis factor receptor family of proteins and pla
ys an important role in the negative regulation of osteoclastic hone resorp
tion, Whether OPG/OCIF circulates in human blood and how its level changes
under pathological conditions is not known. To address these issues, a pane
l of monoclonal antibodies was generated against recombinant OPG/OCIF and s
creened for reactivity with solid-phase monomeric and homodimeric forms of
the recombinant protein. Antibodies that showed high affinity for both form
s of OPG/OCIF and those that selectively recognized the homodimer were iden
tified, enabling development of two types of sensitive enzyme-linked immuno
sorbent assay (ELISA): one that detects both forms of OPG/OCIF equally and
one specific for the homodimer. Characterization of circulating OPG/OCIF wi
th these ELISAs revealed that the protein exists in human serum mainly in t
he monomeric form. The serum concentration of OPG/OCIF increased with age i
n both healthy Japanese men and nomen, and was significantly higher in post
menopausal 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 i
ncreased in those postmenopausal women with a high rate of bone turnover, a
s determined by increased serum bone-specific alkaline phosphatase and urin
ary 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 respo
nse to enhanced osteoclastic bone resorption and the resultant bone loss ra
ther than a cause of osteoporosis.