What is the role of osteoprotegerin (OPG) in the pathogenesis of organ transplantation-related osteoporosis?

Updated: Jul 02, 2020
  • Author: Carmel M Fratianni, MD, FACE; Chief Editor: George T Griffing, MD  more...
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Osteoprotegerin (OPG) is an antiresorptive cytokine and a potential mechanism for immunosuppressant osteopenia. A member of the tumor necrosis factor–receptor superfamily, OPG is a critical regulator of bone resorption. OPG inhibits terminal differentiation and activation of osteoclasts. [64] OPG deficiency causes osteoporosis in mice, and, when administered to ovariectomized rats, OPG decreases osteoclast activity and restores normal bone mass.

OPG is produced by osteoblasts and arterial cells, and inhibits osteoclast function by neutralizing receptor activator of NF-kappa B ligand (RANKL).

Injections of OPG are well tolerated and rapidly decrease markers of bone resorption, urine N -telopeptide, and bone alkaline phosphatase. CsA, rapamycin (sirolimus), and tacrolimus (FK506) significantly decrease OPG mRNA and protein levels in undifferentiated marrow stroma (44-68%). A reciprocal, significant increase in RANKL mRNA levels (60-120%) is also seen with these agents.

In contrast, the potential bone-sparing effect of rapamycin may be explained by the increase in OPG-mRNA seen in mature osteoblasts. [2] Renal transplant recipients treated with intravenous zoledronate (a third-generation bisphosphonate) demonstrated significant elevations of OPG over the first 6 months of treatment, consistent with osteoclast inhibition.

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