Use of spaceflight and spaceflight simulation to evaluate osteoprotegerin for treatment of disuse osteoporosis

Bateman, Ted A.; Stodieck, Louis S.; Kostenuik, Paul J.; Ferguson, Virginia L.; Simske, Steven J.
January 2000
AIP Conference Proceedings;2000, Vol. 504 Issue 1, p580
Academic Journal
Osteoprotegerin (OPG) is a recently discovered naturally circulating protein (Amgen Inc.) that plays a role in regulating bone density. It inhibits the ability of osteoclasts to resorb bone by blocking the action of OPG ligand (OPGL). This limits osteoclastogenesis and the activation of mature osteoclasts and induces osteoclast apoptosis. Transgenic mice, altered to over-express OPG, develop increased bone density via dual X-ray absorptiometry analysis, similar to that of osteopetrotic (op/op) mice. Recombinant injection of OPG in mice increases metaphyseal trabecular bone volume of both the proximal tibia and distal femur. Recombinant OPG also ameliorates the effects of estrogen loss in ovariectomized (OVX) rats, causing an increase in bone volume and decreased osteoclast numbers relative to placebo controls. OPG has been examined for its ability to treat both tail suspension and nerve crush. OPG returns the mechanical properties of tail suspended mice to the levels of placebo treated nonsuspended controls. This increase in mechanical properties is not caused by returning formation levels to normal, but rather by inhibiting resorption while increasing percent mineral composition. OPG is also efficacious in treating nerve crush induced osteoporosis. The differences in bone mass (a consequence of disuse) between the crushed limb and contralateral control (noncrushed) is decreased by OPG treatment. © 2000 American Institute of Physics.


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