title: Cystatin C as a potential predictor of osteoprotegerin levels in healthy men, a cross-sectional, observational study.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  OPG 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.
  
  
  CONCLUSIONS
  The 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.
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. kulcsar.jakab.eva@gmail.com.
authors: Eva
authors: E
authors: Kulcsar-Jakab
authors: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. pethozsofi@hotmail.com.
authors: Zsofia
authors: Z
authors: Petho
authors: Department of Traumatology and Hand Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. papkacsa@gmail.com.
authors: Zoltan
authors: Z
authors: Pap
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. ekalina@med.unideb.hu.
authors: Edit
authors: E
authors: Kalina
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. vfrozika@gmail.com.
authors: Roza
authors: R
authors: Foldesi
authors: Regional Osteoporosis Center, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. balogha@med.unideb.hu.
authors: Adam
authors: A
authors: Balogh
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. antalszp@med.unideb.hu.
authors: Peter
authors: P
authors: Antal-Szalmas
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. harjit@med.unideb.hu.
authors: Harjit Pal
authors: HP
authors: Bhattoa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D015415:Biomarkers; D015519:Bone Density; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood*; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D053245:RANK Ligand / Q000097:blood; D012016:Reference Values; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D024042:Collagen Type I; D055316:Cystatin C; D012739:Gonadal Steroid Hormones; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D010455:Peptides; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; C104450:25-hydroxyvitamin D