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Osteoprotegerin in Serum as a Novel Marker of Bone Metastatic Spread in Prostate Cancer

Departments of
¹ Urology and
² Laboratory Medicine, University Hospital Charité, Humboldt University Berlin, D-10098 Berlin, Germany

^aaddress correspondence to this author at: Department of Urology, Research Division, University Hospital Charité, Humboldt University, Schumannstrasse 20/21, D-10098 Berlin, Germany; fax 4930-450-515904, e-mail klaus.jung@charite.de

Prostate cancer (PCa) is the most frequent carcinoma in men and is often complicated by skeletal metastasis (1). Because bone scintigraphy, the standard method of monitoring metastatic bone involvement, is expensive, lacks specificity, and is not particularly suitable for the follow-up of patients, various metabolic bone markers have been studied as indicators for bone metastasis in PCa patients (2)(3). Markers that reflect osteoblast proliferation, e.g., skeletal alkaline phosphatase (sALP), are reportedly useful, which is consistent with the osteoblastic reactions seen in the skeletal metastases (4).

The balance between osteoblastic and osteoclastic activity in bone is essentially influenced by osteoclastogenesis. The latter is regulated by three proteins: receptor activator of nuclear factor-B (RANK), which is expressed on osteoclast precursor cells; its ligand (RANKL), which is expressed on the surface of preosteoblastic and stromal cells; and osteoprotegerin (5)(6). The interaction of RANKL with RANK stimulates the differentiation of osteoclasts, whereas osteoprotegerin blocks this process by functioning as a decoy receptor for RANKL. This novel cytokine system appears to play an important role in the establishment of bone metastases in PCa patients (7). Osteoprotegerin has recently been found to be overexpressed in bone metastases of these patients (8). This overexpression could indirectly favor osteoblastic reactions by inhibiting osteoclastogenesis and might explain the bone lesions typically seen PCa patients. Because tissue overexpression of proteins often is reflected in blood, osteoprotegerin could be a potential serum marker for diagnosis of bone metastasis.

Using a recently introduced novel osteoprotegerin assay, we performed the present study to evaluate the diagnostic validity of osteoprotegerin as a potential bone metastasis marker in PCa in comparison with sALP and cross-linked N-telopeptides of type I collagen (NTx), which represent osteoblastic and osteoclastic markers, respectively.

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Acknowledgments

References

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				F. Joseph, B. Y. Chan, B. H. Durham, A. M. Ahmad, S. Vinjamuri, J. A. Gallagher, J. P. Vora, and W. D. Fraser The Circadian Rhythm of Osteoprotegerin and Its Association with Parathyroid Hormone Secretion J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3230 - 3238. [Abstract] [Full Text] [PDF]

				D. J. Leeming, M. Koizumi, I. Byrjalsen, B. Li, P. Qvist, and L. B. Tanko The Relative Use of Eight Collagenous and Noncollagenous Markers for Diagnosis of Skeletal Metastases in Breast, Prostate, or Lung Cancer Patients Cancer Epidemiol. Biomarkers Prev., January 1, 2006; 15(1): 32 - 38. [Abstract] [Full Text] [PDF]

				A. Rogers and R. Eastell Circulating Osteoprotegerin and Receptor Activator for Nuclear Factor {kappa}B Ligand: Clinical Utility in Metabolic Bone Disease Assessment J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6323 - 6331. [Abstract] [Full Text] [PDF]

				B. Fohr, C. R. Dunstan, and M. J. Seibel Markers of Bone Remodeling in Metastatic Bone Disease J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5059 - 5075. [Abstract] [Full Text] [PDF]

				A. Dovio, M. L. Sartori, and A. Angeli Correspondence re: A. Lipton et al., Serum Osteoprotegerin Levels in Healthy Controls and Cancer Patients. Clin. Cancer Res., 8: 2306-2310, 2002. Clin. Cancer Res., June 1, 2003; 9(6): 2384 - 2385. [Full Text] [PDF]

				O. Sezer, U. Heider, I. Zavrski, C. A. Kuhne, and L. C. Hofbauer RANK ligand and osteoprotegerin in myeloma bone disease Blood, March 15, 2003; 101(6): 2094 - 2098. [Abstract] [Full Text] [PDF]