Cystatin C As a Potential Predictor of Osteoprotegerin Levels in Healthy Men, a Cross-sectional, Observational Study

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2015 Aug 28

PMID 26311162

Citations 4

Authors

Eva Kulcsar-Jakab

Zsofia Petho

Zoltan Pap

Edit Kalina

Roza Foldesi

Adam Balogh

Peter Antal-Szalmas

Harjit Pal Bhattoa

Affiliations

Soon will be listed here.

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.

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References

Jorgensen L, Vik A, Emaus N, Brox J, Hansen J, Mathiesen E . Bone loss in relation to serum levels of osteoprotegerin and nuclear factor-kappaB ligand: the Tromsø Study. Osteoporos Int. 2009; 21(6):931-8. DOI: 10.1007/s00198-009-1035-6. View

Lee S, Lorenzo J . Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology. 1999; 140(8):3552-61. DOI: 10.1210/endo.140.8.6887. View

Inker L, Schmid C, Tighiouart H, Eckfeldt J, Feldman H, Greene T . Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012; 367(1):20-9. PMC: 4398023. DOI: 10.1056/NEJMoa1114248. View

Teitelbaum S . Bone resorption by osteoclasts. Science. 2000; 289(5484):1504-8. DOI: 10.1126/science.289.5484.1504. View

Murakami T, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K . Transforming growth factor-beta1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem Biophys Res Commun. 1998; 252(3):747-52. DOI: 10.1006/bbrc.1998.9723. View

Mazziotti G, Amato G, Sorvillo F, Piscopo M, Rizzo M, Lalli E . Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism. Eur J Endocrinol. 2006; 154(3):373-7. DOI: 10.1530/eje.1.02099. View

Simonet W, Lacey D, Dunstan C, Kelley M, Chang M, Luthy R . Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89(2):309-19. DOI: 10.1016/s0092-8674(00)80209-3. View

Szulc P, Hawa G, Boutroy S, Vilayphiou N, Schoppet M, Chapurlat R . Cortical bone status is associated with serum osteoprotegerin concentration in men: the STRAMBO study. J Clin Endocrinol Metab. 2011; 96(7):2216-26. DOI: 10.1210/jc.2010-2617. View

Khosla S . Minireview: the OPG/RANKL/RANK system. Endocrinology. 2001; 142(12):5050-5. DOI: 10.1210/endo.142.12.8536. View

10.

Hofbauer L, Heufelder A . Clinical review 114: hot topic. The role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic bone diseases. J Clin Endocrinol Metab. 2000; 85(7):2355-63. DOI: 10.1210/jcem.85.7.6702. View

11.

Teo B, Sabanayagam C, Liao J, Toh Q, Saw S, Wong T . Comparison of CKD-EPI Cystatin C and Creatinine Glomerular Filtration Rate Estimation Equations in Asian Indians. Int J Nephrol. 2014; 2014:746497. PMC: 4020461. DOI: 10.1155/2014/746497. View

12.

Vega D, Maalouf N, Sakhaee K . CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 2007; 92(12):4514-21. DOI: 10.1210/jc.2007-0646. View

13.

Samelson E, Broe K, Demissie S, Beck T, Karasik D, Kathiresan S . Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip. J Clin Endocrinol Metab. 2008; 93(5):1789-95. PMC: 2386280. DOI: 10.1210/jc.2007-2492. View

14.

Khosla S, Arrighi H, Melton 3rd L, Atkinson E, OFallon W, Dunstan C . Correlates of osteoprotegerin levels in women and men. Osteoporos Int. 2002; 13(5):394-9. DOI: 10.1007/s001980200045. View

15.

Onyia J, Miles R, Yang X, Halladay D, Hale J, Glasebrook A . In vivo demonstration that human parathyroid hormone 1-38 inhibits the expression of osteoprotegerin in bone with the kinetics of an immediate early gene. J Bone Miner Res. 2000; 15(5):863-71. DOI: 10.1359/jbmr.2000.15.5.863. View

16.

Bhattoa H, Nagy E, More C, Kappelmayer J, Balogh A, Kalina E . Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age: the HunMen Study. Osteoporos Int. 2012; 24(1):179-86. DOI: 10.1007/s00198-012-1920-2. View

17.

Trofimov S, Pantsulaia I, Pantsulaia I, Kobyliansky E, Livshits G . Circulating levels of receptor activator of nuclear factor-kappaB ligand/osteoprotegerin/macrophage-colony stimulating factor in a presumably healthy human population. Eur J Endocrinol. 2004; 150(3):305-11. DOI: 10.1530/eje.0.1500305. View

18.

Oh K, Rhee E, Lee W, Kim S, Baek K, Kang M . Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol (Oxf). 2005; 62(1):92-8. DOI: 10.1111/j.1365-2265.2004.02179.x. View

19.

Indridason O, Franzson L, Sigurdsson G . Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover. Osteoporos Int. 2005; 16(4):417-23. DOI: 10.1007/s00198-004-1699-x. View

20.

Stern A, Laughlin G, Bergstrom J, Barrett-Connor E . The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study. Eur J Endocrinol. 2007; 156(5):555-62. PMC: 2642656. DOI: 10.1530/EJE-06-0753. View