Abstract
Sclerostin has been proposed as a potent inhibitor of bone formation. Sclerostin antibodies are under clinical development to treat osteoporosis and metastatic bone disease. Serum sclerostin level is elevated in multiple myeloma, an osteolytic malignancy, where it might serve as predictive marker for the use of sclerostin-directed antibodies. As renal cell carcinoma (RCC) patients often present with osteolytic metastases, we aimed to investigate serum sclerostin levels in RCC patients. Our study included 53 RCC patients (19 with bone metastases, 25 with visceral metastases and 9 with localized disease) and 53 age- and gender-matched non-osteoporotic controls. Frozen serum samples were subjected to sclerostin quantitative sandwich ELISA. The mean serum sclerostin levels of RCC patients and controls were 45.8 pmol/l and 45.1 pmol/l, respectively (p = 0.86). Analysis of variance showed no difference between the subgroups of RCC patients with regard to visceral or bone metastases or localized disease (p = 0.22). There was no significant association between eGFR (estimated glomerular filtration rate) and serum sclerostin levels in RCC patients (r = 0.05; p = 0.74) and controls (r = 0.06; p = 0.68). Our results indicate that serum sclerostin levels appear not to be a valuable biomarker to assess the occurrence of bone metastases in RCC patients.
Highlights
Sclerostin is a glycoprotein with a C-terminal cysteine-knot-like (CTCK) domain and is encoded by the SOST gene
Since there are no reports to date on serum sclerostin levels in Renal cell carcinoma (RCC), we systematically evaluated them in different groups of RCC patients: patients with localized disease, bone or visceral metastases and compared them to serum sclerostin levels in non-osteoporotic controls
There was no difference between the serum sclerostin levels of RCC patients and controls (p = 0.86) (Fig. 1)
Summary
Sclerostin is a glycoprotein with a C-terminal cysteine-knot-like (CTCK) domain and is encoded by the SOST gene. Wijenayaka et al.[2] first described the pathway that underlies the influence of sclerostin on bone formation They reported that sclerostin inhibits the Wnt/ß-catenin pathway by inhibiting low-density lipoprotein receptor-related protein 5 (Lrp[5]). In metastatic bone disease (MBD) there is evidence that Wnt-regulating molecules such as sclerostin contribute to the development and progression of osteoblastic and/or osteolytic metastases, depending on the rate of expression[11,16]. Renal cell carcinoma (RCC) accounts for approximately 4% of all malignancies in Western Europe and the USA; the age-adjusted incidence rate lies between 6.2-8.4/100,000/year, and the male to female ratio is 3:219,20 It occurs less frequently in developing countries[21]. Since there are no reports to date on serum sclerostin levels in RCC, we systematically evaluated them in different groups of RCC patients: patients with localized disease, bone or visceral metastases and compared them to serum sclerostin levels in non-osteoporotic controls
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