Skip to main content
SpringerLink
Log in

Age- and sex-specific concentrations of bone remodeling markers in healthy Indian adults with and without vitamin D deficiency

  • Original Article
  • Published:
Archives of Osteoporosis Aims and scope Submit manuscript

Abstract

Summary

Bone remodeling markers exhibit marked inter-ethnic variation; hence, population-specific data are required. Herein, we have established age- and sex-specific concentrations of serum PINP and CTX in healthy Indian adults with and without vitamin D deficiency that can be used in clinical practice for monitoring response to anti-osteoporotic therapy.

Objective

The present study was undertaken to generate data on age- and sex-specific concentrations of serum procollagen type I N-propeptide (PINP) and type I collagen C-telopeptide (CTX) in healthy Indian adults with and without vitamin D deficiency.

Methods

Apparently, healthy subjects aged ≥ 20 years with no prior co-morbidities were recruited from the community by door-to-door surveys. Provisionally eligible participants underwent blood sampling after overnight fast. Individuals with biochemical abnormalities that could potentially affect bone remodeling were excluded. However, subjects with vitamin D deficiency were not excluded. Serum total PINP and β-CrossLaps (CTX) were measured using electro-chemiluminescence immunoassay.

Results

After exclusion, 677 subjects were enrolled (M:F = 2.5:4.2, mean age = 45.0 years). Median serum PINP and CTX were 55.78 ng/ml (40.27–71.70) and 0.356 ng/ml (0.238–0.499), respectively. There was no difference in PINP/CTX between men and women or between premenopausal and postmenopausal women. Decade-wise distribution of PINP/CTX showed that maximum values were attained in 3rd decade; subsequently, in men, levels declined with age while in women, there was a peak in the 6th decade coinciding with the early years of menopause. Vitamin D deficiency and severe vitamin D deficiency were seen in 417 (61.5%) and 259 subjects (38.2%), respectively. There was no significant difference in PINP/CTX in subjects with and without vitamin D deficiency.

Conclusions

The present study has allowed us to generate data on serum concentrations of PINP/CTX in a diverse group of healthy community-dwelling Indian adults with varying serum vitamin D levels. It might aid in monitoring response to anti-osteoporotic therapy amongst native Indians.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Available on request to the corresponding author.

References

  1. Starup-Linde J, Vestergaard P (2016) Biochemical bone turnover markers in diabetes mellitus — a systematic review. Bone 82:69–78. https://doi.org/10.1016/j.bone.2015.02.019

    Article  CAS  PubMed  Google Scholar 

  2. Camacho PM, Petak SM, Binkley N, Clarke BL, Harris ST, Hurley DL, Kleerekoper M, Lewiecki EM, Miller PD, Narula HS, Pessah-Pollack R, Tangpricha V, Wimalawansa SJ, Watts NB (2016) American Association Of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis — 2016-- executive summary. Endocr Pract 22:1111–1118. https://doi.org/10.4158/EP161435.ESGL

    Article  PubMed  Google Scholar 

  3. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis Foundation (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381. https://doi.org/10.1007/s00198-014-2794-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N, Ohta H, Shiraki M, Sugimoto T, Suzuki T, Soen S, Nishizawa Y, Hagino H, Fukunaga M, Fujiwara S (2011) Japanese guidelines for prevention and treatment of osteoporosis—executive summary. Arch Osteoporos 7:3–20. https://doi.org/10.1007/s11657-012-0109-9

    Article  Google Scholar 

  5. Hwang J-S, Chan D-C, Chen J-F, Cheng TT, Wu CH, Soong YK, Tsai KS, Yang RS (2014) Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary. J Bone Miner Metab 32:10–16. https://doi.org/10.1007/s00774-013-0495-0

    Article  PubMed  Google Scholar 

  6. Vasikaran S, Bruyère O, Foldes AJ et al (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420. https://doi.org/10.1007/s00198-010-1501-1

    Article  CAS  PubMed  Google Scholar 

  7. Shetty S, Kapoor N, Bondu J et al (2016) Bone turnover markers: emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 20:846. https://doi.org/10.4103/2230-8210.192914

    Article  PubMed  PubMed Central  Google Scholar 

  8. de Papp AE, Bone HG, Caulfield MP, Kagan R, Buinewicz A, Chen E, Rosenberg E, Reitz RE (2007) A cross-sectional study of bone turnover markers in healthy premenopausal women. Bone 40:1222–1230. https://doi.org/10.1016/j.bone.2007.01.008

    Article  PubMed  Google Scholar 

  9. Finkelstein JS, Sowers M, Greendale GA, Lee MLT, Neer RM, Cauley JA, Ettinger B (2002) Ethnic variation in bone turnover in pre- and early perimenopausal women: effects of anthropometric and lifestyle factors. J Clin Endocrinol Metab 87:3051–3056. https://doi.org/10.1210/jcem.87.7.8480

    Article  CAS  PubMed  Google Scholar 

  10. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J (2000) The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 11:S2–S17. https://doi.org/10.1007/s001980070002

    Article  PubMed  Google Scholar 

  11. Szulc P (2012) The role of bone turnover markers in monitoring treatment in postmenopausal osteoporosis. Clin Biochem 45:907–919. https://doi.org/10.1016/j.clinbiochem.2012.01.022

    Article  CAS  PubMed  Google Scholar 

  12. Dreyer P, Vieira JGH (2010) Bone turnover assessment: a good surrogate marker? Arq Bras Endocrinol Metabol 54:99–105. https://doi.org/10.1590/s0004-27302010000200003

    Article  PubMed  Google Scholar 

  13. Glover SJ, Gall M, Schoenborn-Kellenberger O, Wagener M, Garnero P, Boonen S, Cauley JA, Black DM, Delmas PD, Eastell R (2009) Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium, and the United States. J Bone Miner Res 24:389–397. https://doi.org/10.1359/jbmr.080703

    Article  PubMed  Google Scholar 

  14. Gossiel F, Finigan J, Jacques R, Reid D, Felsenberg D, Roux C, Glueer C, Eastell R (2014) Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state. BoneKEy Rep 3. https://doi.org/10.1038/bonekey.2014.68

  15. Eastell R, Garnero P, Audebert C, Cahall DL (2012) Reference intervals of bone turnover markers in healthy premenopausal women: results from a cross-sectional European study. Bone 50:1141–1147. https://doi.org/10.1016/j.bone.2012.02.003

    Article  PubMed  Google Scholar 

  16. Michelsen J, Wallaschofski H, Friedrich N, Spielhagen C, Rettig R, Ittermann T, Nauck M, Hannemann A (2013) Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone 57:399–404. https://doi.org/10.1016/j.bone.2013.09.010

    Article  CAS  PubMed  Google Scholar 

  17. Jenkins N, Black M, Paul E, Pasco JA, Kotowicz MA, Schneider HG (2013) Age-related reference intervals for bone turnover markers from an Australian reference population. Bone 55:271–276. https://doi.org/10.1016/j.bone.2013.04.003

    Article  CAS  PubMed  Google Scholar 

  18. Hu W-W, Zhang Z, He J-W, Fu WZ, Wang C, Zhang H, Yue H, Gu JM, Zhang ZL (2013) Establishing reference intervals for bone turnover markers in the healthy Shanghai population and the relationship with bone mineral density in postmenopausal women. Int J Endocrinol 2013:1–7. https://doi.org/10.1155/2013/513925

    Article  CAS  Google Scholar 

  19. Kushida K, Takahashi M, Kawana K, Inoue T (1995) Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients. J Clin Endocrinol Metab 80:2447–2450. https://doi.org/10.1210/jcem.80.8.7629240

    Article  CAS  PubMed  Google Scholar 

  20. Cho DH, Chung JO, Chung MY et al (2020) Reference intervals for bone turnover markers in Korean healthy women. J Bone Metab 27:43–52. https://doi.org/10.11005/jbm.2020.27.1.43

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ardawi M-SM, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Raddadi RM (2010) Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study. Bone 47:804–814. https://doi.org/10.1016/j.bone.2010.07.017

    Article  CAS  PubMed  Google Scholar 

  22. Tan KML, Saw S, Sethi SK (2013) Vitamin D and its relationship with markers of bone metabolism in healthy Asian women: vitamin D levels in healthy Asian women. J Clin Lab Anal 27:301–304. https://doi.org/10.1002/jcla.21602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kharroubi A, Saba E, Smoom R, Bader K, Darwish H (2017) Serum 25-hydroxyvitamin D and bone turnover markers in Palestinian postmenopausal osteoporosis and normal women. Arch Osteoporos 12:13. https://doi.org/10.1007/s11657-017-0306-7

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lowe NM, Mitra SR, Foster PC, Bhojani I, McCann JF (2010) Vitamin D status and markers of bone turnover in Caucasian and South Asian postmenopausal women living in the UK. Br J Nutr 103:1706–1710. https://doi.org/10.1017/S0007114509993850

    Article  CAS  PubMed  Google Scholar 

  25. So J, Park H (2004) Relationship between parathyroid hormone, vitamin D and bone turnover markers in Korean postmenopausal women. Korean J Obstet Gynecol 47:153–160

    Google Scholar 

  26. Hill TR, O’Brien MM, Lamberg-Allardt C et al (2006) Vitamin D status of 51–75-year-old Irish women: its determinants and impact on biochemical indices of bone turnover. Public Health Nutr 9:225–233. https://doi.org/10.1079/PHN2005837

    Article  PubMed  Google Scholar 

  27. Kumar A, Devi SG, Mittal S, Shukla DK, Sharma S (2013) A hospital based study of biochemical markers of bone turnovers & bone mineral density in north Indian women. Indian J Med Res 137:48–56

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Shetty S, Kapoor N, Dian Bondu J, Antonisamy B, Thomas N, Paul TV (2016) Bone turnover markers and bone mineral density in healthy mother-daughter pairs from South India. Clin Endocrinol (Oxf) 85:725–732. https://doi.org/10.1111/cen.13173

    Article  CAS  Google Scholar 

  29. Gupta R, Gupta A (2014) Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients 6:729–775. https://doi.org/10.3390/nu6020729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Aparna P, Muthathal S, Nongkynrih B, Gupta S (2018) Vitamin D deficiency in India. J Fam Med Prim Care 7:324–330. https://doi.org/10.4103/jfmpc.jfmpc_78_18

    Article  CAS  Google Scholar 

  31. Aggarwal A, Ram S, Garg A, Pal R, Bhansali A, Singh P, Sharma S, Thakur JS, Sachdeva N, Bhadada SK (2019) Metabolic bone profile of healthy adult north indian population from Chandigarh Urban Bone Epidemiological Study (CUBES). Indian J Clin Biochem. https://doi.org/10.1007/s12291-019-00857-6

  32. Srivastava SK, Chand R (2017) Tracking transition in calorie-intake among Indian households: Insights and policy implications. Agric Econ Res Rev 30:23. https://doi.org/10.5958/0974-0279.2017.00002.7

    Article  Google Scholar 

  33. Janssen I, Ross R (2012) Vigorous intensity physical activity is related to the metabolic syndrome independent of the physical activity dose. Int J Epidemiol 41:1132–1140. https://doi.org/10.1093/ije/dys038

    Article  PubMed  PubMed Central  Google Scholar 

  34. Longvah T, Ananthan R, Bhaskarachary K, Venkaiah K (2017) Indian food composition tables

  35. Szulc P, Kaufman JM, Delmas PD (2007) Biochemical assessment of bone turnover and bone fragility in men. Osteoporos Int 18:1451–1461. https://doi.org/10.1007/s00198-007-0407-z

    Article  CAS  PubMed  Google Scholar 

  36. Gundberg CM, Looker AC, Nieman SD, Calvo MS (2002) Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity. Bone 31:703–708. https://doi.org/10.1016/S8756-3282(02)00902-X

    Article  CAS  PubMed  Google Scholar 

  37. Holvik K, Meyer HE, Søgaard AJ, Selmer R, Haug E, Falch JA (2006) Biochemical markers of bone turnover and their relation to forearm bone mineral density in persons of Pakistani and Norwegian background living in Oslo, Norway: The Oslo Health Study. Eur J Endocrinol 155:693–699. https://doi.org/10.1530/eje.1.02282

    Article  CAS  PubMed  Google Scholar 

  38. Hamson C (2003) Comparative study of bone mineral density, calcium, and vitamin D status in the Gujarati and white populations of Leicester. Postgrad Med J 79:279–283. https://doi.org/10.1136/pmj.79.931.279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Madar AA, Knutsen KV, Stene LC, Brekke M, Lagerløv P, Meyer HE, Macdonald HM (2015) Effect of vitamin D3-supplementation on bone markers (serum P1NP and CTX): a randomized, double blinded, placebo controlled trial among healthy immigrants living in Norway. Bone Rep 2:82–88. https://doi.org/10.1016/j.bonr.2015.05.004

    Article  PubMed  PubMed Central  Google Scholar 

  40. Seamans KM, Hill TR, Wallace JMW, Horigan G, Lucey AJ, Barnes MS, Taylor N, Bonham MP, Muldowney S, Duffy EM, Strain JJ, Kiely M, Cashman KD (2010) Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults. J Nutr 140:454–460. https://doi.org/10.3945/jn.109.113480

    Article  CAS  PubMed  Google Scholar 

  41. Schwetz V, Trummer C, Pandis M, Grübler M, Verheyen N, Gaksch M, Zittermann A, März W, Aberer F, Lang A, Treiber G, Friedl C, Obermayer-Pietsch B, Pieber T, Tomaschitz A, Pilz S (2017) Effects of vitamin D supplementation on bone turnover markers: a randomized controlled trial. Nutrients 9:432. https://doi.org/10.3390/nu9050432

    Article  CAS  PubMed Central  Google Scholar 

  42. Seamans KM, Cashman KD (2009) Existing and potentially novel functional markers of vitamin D status: a systematic review. Am J Clin Nutr 89:1997S–2008S. https://doi.org/10.3945/ajcn.2009.27230D

    Article  CAS  PubMed  Google Scholar 

  43. Szulc P, Garnero P, Munoz F, Marchand F, Delmas PD (2001) Cross-sectional evaluation of bone metabolism in men*. J Bone Miner Res 16:1642–1650. https://doi.org/10.1359/jbmr.2001.16.9.1642

    Article  CAS  PubMed  Google Scholar 

  44. Khosla S, Melton LJ, Atkinson EJ et al (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274. https://doi.org/10.1210/jcem.83.7.4924

    Article  CAS  PubMed  Google Scholar 

  45. Kenny AM, Gallagher JC, Prestwood KM, Gruman CA, Raisz LG (1998) Bone density, bone turnover, and hormone levels in men over age 75. J Gerontol A Biol Sci Med Sci 53A:M419–M425. https://doi.org/10.1093/gerona/53A.6.M419

    Article  CAS  Google Scholar 

  46. Lumachi F, Orlando R, Fallo F, Basso SMM (2012) Relationship between bone formation markers bone alkaline phosphatase, osteocalcin and amino-terminal propeptide of type I collagen and bone mineral density in elderly men. Preliminary results. Vivo Athens Greece 26:1041–1044

    Google Scholar 

  47. Dennison E, Eastell R, Fall CHD, Kellingray S, Wood PJ, Cooper C (1999) Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 10:384–391. https://doi.org/10.1007/s001980050244

    Article  CAS  PubMed  Google Scholar 

  48. Scopacasa F, Wishart JM, Need AG, Horowitz M, Morris HA, Nordin BEC (2002) Bone density and bone-related biochemical variables in normal men: a longitudinal study. J Gerontol A Biol Sci Med Sci 57:M385–M391. https://doi.org/10.1093/gerona/57.6.M385

    Article  CAS  PubMed  Google Scholar 

  49. Yoshimura N, Hashimoto T, Sakata K, Morioka S, Kasamatsu T, Cooper C (1999) Biochemical markers of bone turnover and bone loss at the lumbar spine and femoral neck: the Taiji Study. Calcif Tissue Int 65:198–202. https://doi.org/10.1007/s002239900682

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Rimesh Pal, Anshita Aggarwal, Naresh Sachdeva, Abhilasha Garg, Anil Bhansali & Sanjay Kumar Bhadada

  2. Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Sant Ram

Authors
  1. Rimesh Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anshita Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naresh Sachdeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sant Ram
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abhilasha Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anil Bhansali
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sanjay Kumar Bhadada
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analyses were performed by Rimesh Pal, Sanjay Kumar Bhadada, and Anshita Aggarwal. The first draft of the manuscript was written by Rimesh Pal and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sanjay Kumar Bhadada.

Ethics declarations

Conflicts of interest

None.

Ethics approval

The study was approved by the Institute Ethical Committee, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Code availability

Not applicable

Consent to participate

Written informed consent was obtained

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Figure S1A-B.

Box and whisker plots showing decade-wise distribution of serum concentrations of procollagen type I N-propeptide (PINP) (figure S1A) and I collagen C-telopeptide (CTX) (figure S1B) in women. Women in their sixth decade (50-59 years) had significantly higher PINP (p=0.03) and CTX (p=0.048) as compared to women in their fifth decade (40-49 years). (JPG 135 kb)

Supplementary Figure S2A-B.

Scatterplots with LOESS curves showing the relation between serum concentrations of procollagen type I N-propeptide (PINP) (figure S2A) and type I collagen C-telopeptide (CTX) (figure S2B) and age in premenopausal women (n=257). (JPG 152 kb)

Supplementary Figure S3A-B.

Scatterplots with LOESS curves showing the relation between serum concentrations of procollagen type I N-propeptide (PINP) (figure S3A) and type I collagen C-telopeptide (CTX) (figure S3B) and years since menopause in postmenopausal women (n=162). (JPG 150 kb)

ESM 4

(DOC 35 kb)

ESM 5

(DOC 29 kb)

ESM 6

(DOC 30 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pal, R., Aggarwal, A., Sachdeva, N. et al. Age- and sex-specific concentrations of bone remodeling markers in healthy Indian adults with and without vitamin D deficiency. Arch Osteoporos 16, 10 (2021). https://doi.org/10.1007/s11657-020-00855-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11657-020-00855-9

Keywords

Search

Navigation