Cystatin C as a potential predictor of osteoprotegerin levels in healthy men, a cross-sectional, observational study

Abstract

BackgroundThe aim of the present study is to evaluate serum osteoprotegerin (OPG) and soluble receptor activator of nuclear factor κB ligand (sRANKL) levels in a randomly selected male cohort over 50 years of age and its association with cystatin C, a cysteine proteinase inhibitor that decreases formation of osteoclasts by interfering at a late stage of pre-osteoclast differentiation, apart from being a marker of renal function independent of gender, muscle mass and age; in addition to known predictors such as age, sex hormones, vitamin D, bone mineral density (BMD) and biochemical markers of bone turnover.MethodsWe determined serum OPG and sRANKL levels and examined its relationship with cystatin C, age, osteocalcin, C-terminal telopeptides of type-I collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D, parathyroid hormone, total 17β-estradiol (E2), total testosterone and L1–L4 (LS) and femur neck (FN) BMD data available from 194 (age, range: 51–81 years) randomly selected ambulatory men belonging to the HunMen cohort.ResultsOPG correlated significantly with age (Spearman’s rho (r) = 0.359, p < 0.001), cystatin C (r = 0.298, p < 0.001), E2 (r = 0.160, p = 0.028) and free testosterone index (FTI) (r = −0.230, p = 0.001). Compared to the middle-aged (age: ≤ 59 years, n = 98), older men (age > 59 years, n = 96) had significantly higher serum OPG (4.6 pmol/L vs. 5.4 pmol/L; p < 0.001), and lower sRANKL (0.226 pmol/L vs. 0.167 pmol/L; p = 0.048) levels. The older men showed a significant correlation between serum OPG levels and cystatin C (Spearman’s rho = 0.322, p = 0.002), and E2 (Spearman’s rho = 0.211, p = 0.043). Including cystatin C and E2 in a regression model showed that cystatin C (standard regression coefficient (β) = 0.345; p = 0.002) was the only significant predictor of serum OPG levels in the older men.ConclusionsThe results of this study demonstrated that in addition to age (which was the stronger predictor), other modifiable factors such as cystatin C, FTI and E2 were also significant predictors of OPG, and that the association between cystatin C and OPG was more evident with increased age (older age group). As such, cystatin C is a significant predictor of OPG independently of age, FTI and E2.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0684-1) contains supplementary material, which is available to authorized users.

Osteoprotegerin as a marker of cardiovascular risk in children and adolescents with type 1 diabetes

“…In this context, we also found a significant positive correlation with cystatin‐C. In a recent observational study, Kulcsar‐Jakab et al demonstrated that cystatin‐C is a potential predictor of OPG levels in healthy men. Moreover, It has been shown that cystatin‐C could be used as a marker for cardiovascular risk assessment .…”

Up‐regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF‐κB pathway

“…The role of CST5 was previously revealed in colorectal cancer, in which loss of CST5 promoted tumour differentiation while induction of CST5 exerted a tumour‐suppressive effect on colorectal cancer . More importantly, as a cysteine proteinase inhibitor, CST5 could restrain osteoclast formation through interference of late‐staged differentiation of pre‐osteoclasts . TRAP was known to be an osteoclast marker, and the increased expression of TRAP was exhibited in osteoblasts and osteocytes in experimental OP rats .…”

“…CST5, a cysteine protease inhibitor, has been reported to be associated with tumour suppression, but there was little research focusing on the effect of CST5 on OP. The role of another cysteine protease inhibitor, CST3, was reported to reduce the formation of osteoclasts by interfering with the late differentiation of osteoclast precursors . Studies have shown that inhibition of the NF‐κB pathway could relieve OP .…”

“…11,26 More importantly, as a cysteine proteinase inhibitor, CST5 could restrain osteoclast formation through interference of late-staged differentiation of preosteoclasts. 21 TRAP was known to be an osteoclast marker, and the increased expression of TRAP was exhibited in osteoblasts and osteocytes in experimental OP rats. 27 Elevated expression of alkaline phosphatase (ALP) derived from bones and liver was closely associated with bone metabolic marker BAP, and elevation of ALP resulted from bone turnover in postmenopausal osteoporotic women.…”

“…The role of another cysteine protease inhibitor, CST3, was reported to reduce the formation of osteoclasts by interfering with the late differentiation of osteoclast precursors. 21 Studies have shown that inhibition of the NF-κB pathway could relieve OP. 22,23 Moreover, cystatin was demonstrated to affect the NF-κB pathway.…”