2019 | 3 | 270-276
Article title

The effect of chronic exercise on a biomarker of bone resorption in healthy adults

Title variants
Languages of publication
Background. Long-term exercise contributes to the inhibition of osteoblast cell activity and to the decrease of bone resorption. Objectives. The research objective was to analyze the chronic effect of regular, long-term physical activity and physical inactivity on carboxyterminal collagen cross-linking telopeptide levels (CTx) and calcium levels in healthy adults. Material and methods. This study was a prospective cohort study. Fifty-four men and women, aged 17–26 years, were divided into 2 groups of 27 people each: exercise and non-exercise. This research was carried out from April 2015 to April 2016 at the Faculty of Medicine, Syiah Kuala University, Aceh, Indonesia. Bone resorption can be determined by measuring the carboxyterminal cross-linking telopeptide of collagen (CTx). The data were analyzed using Student’s t-test and regression correlation analysis with a significance level of 5%. Results. The highest levels of CTx were found in the non-exercise group; the lowest levels of CTx were in the exercise group (1.6 ng/mL and 0.30 ng/mL, respectively). This difference in CTx levels between groups was statistically significant (0.52 ± 0.22 ng/mL vs 0.72 ± 0.28 ng/mL; p = 0.005). Calcium was significantly higher in the exercise group than in the non-exercise one (9.67 ± 0.30 vs 9.01 ± 0.21 mg/dl; p = 0.006). There was a negative correlation between calcium levels and CTx in the exercise group (r = 0.038; p = 0.001). Conclusions. Regular exercise led to lower CTx levels and increased calcium levels. The increase in calcium is an effect of the decrease in CTx in healthy adults. Regular exercise decreases bone resorption and increases bone calcium
  • Gombos GC, Bajsz V, Pék E, et al. Direct effects of physical training on markers of bone metabolism and serum sclerostin concentrations in older adults with low bone mass. BMC Musculoskelet Disord 2016; 17(254): 1–8, doi: 10.1186/s12891-016-1109-5.
  • Castrogiovanni P, Trovato FM, Szychlinska MA, et al. The importance of physical activity in osteoporosis. From the molecular pathways to the clinical evidence. Histol Histopathol 2016; 31: 1183–1194, doi: 10.14670/HH-11-793.
  • Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol 2017; 4: 46–56, doi: 10.5152/eurjrheum.2016.048.
  • Denise L, Moreira F, Oliveira ML De. Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women. Arq Bras Endocrinol Metab 2014; 58(5): 514–522, doi: 10.1590/0004-2730000003374.
  • Michalska-Kasiczak M, Jegier A, Sewerynek E. Effects of physical activity on sclerostin concentrations. Endokrynol Pol 2018; 69(2): 142–149, doi: 10.5603/EP.
  • Tu KN, Lie JD, King C, et al. Osteoporosis: a review of treatment options. PT 2018; 43(2): 92–104.
  • Drake MT, Clarke BL, Lewiecki EM. The pathophysiology and treatment of osteoporosis. Clin Ther 2015; 1(1): 1–14, doi: 10.1016/j.clinthera.2015.06.006.
  • Garnero P. The utility of biomarkers in osteoporosis management. Mol Diagn Ther 2017: 1–18, doi: 10.1007/s40291-017-0272-1.
  • 9. Chavassieux P, Portero-Muzy N, Roux J, et al. Are biochemical markers of bone turnover representative of bone histomorphometry in 370 postmenopausal women? J Clin Endocrinol Metab 2015; 100(12): 4662–4668, doi: 10.1210/jc.2015-2957.
  • Garnero P, Costa AG, Aderson M, et al. Bone markers and osteoporosis therapy. Arq Bras Endocrinol Metab 2014; 58(5): 504–513, doi: 10.1590/0004-2730000003384.
  • Bhattoa HP. Laboratory aspects and clinical utility of bone turnover markers. J Int Fed Clin Chem Lab Med 2018; 29(2): 117–128.
  • Sousa CP, Dias IR, Lopez-Peña M, et al. Bone turnover markers for early detection of fracture healing disturbances: a review of the scientific literature. Ann Brazilian Acad Sci 2015; 87(2): 1049–1061.
  • Kuo T, Chen C. Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomarker Research 2017; 5(18): 5–13, doi: 10.1186/s40364-017-0097-4.
  • Gasser JA, Kneissel M. Bone physiology and biology. Bone Toxicol 2017: 27–94, doi: 10.1007/978-3-319-56192-9.
  • Rouhi G, Mosafer S. Biomechanics of osteoporosis: The importance of bone resorption and remodeling processes. In: Dionyssiotis Y, ed. Osteoporosis. InTech; 2012: 59–77, doi: 10.5772/29987.
  • Faiz M, Rahim A, Shaharudin S. Changes of bone metabolism markers following additional isokinetic and isotonic training and its subsequent cessation in advanced level adolescent weightlifters. Acta Gymnica 2018; 48(4): 175–181, doi: 10.5507/ag.2018.024.
  • Hlaing TT, Compston JE. Biochemical markers of bone turnover – uses and limitations. Ann Clin Biochem 2014; 51(Pt 2): 189–202, doi:10.1177/0004563213515190.
  • Bandeira F, Costa AG, Filho MAS, et al. Bone markers and osteoporosis therapy. Arq Bras Endocrinol Metab 2014; 58(5): 504–513.
  • Khashayar P, Meybodi HA, Amoabediny G. Biochemical markers of bone turnover and their role in osteoporosis diagnosis: a narrative
  • review. Recent Pat Endocr Metab Immune Drug Discov 2015; 9(2): 79–89.
  • Florencio-Silva R, Rodrigues G, Sasso-Cerri E, et al. Biology of bone tissue: structure, function, and factors that influence bone cells.Biomed Res Int 2015; 421746, doi: 10.1155/2015/421746.
  • Langdahl B, Ferrari S, Dempster DW. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.Ther Adv Musculoskelet Dis 2016; 8(6): 225–235, doi: 10.1177/1759720X16670154.
  • Amirouche F, Bobko A. Bone remodeling and biomechanical processes – a multiphysics approach. Austin J Biotechnol Bioeng 2015;2(2): 1–11.
  • Kenkre JS, Bassett JHD. The bone remodelling cycle. Ann Clin Biochem 2018; 55(3): 308–327, doi: 10.1177/0004563218759371.
  • . Kini U, Nandeesh BN. Physiology of bone formation, remodeling, and metabolism. In: Radionuclide and hybrid bone imaging. Berlin–Heidelberg: Springer-Verlag; 2012: 29–57, doi: 10.1007/978-3-642-02400-9.
  • Warren M, Whiting S, Bonjour J, et al. Biochemical markers for assessment of calcium economy and bone metabolism: application in clinical trials from pharmaceutical agents to nutritional products. Nutr Res Rev 2014; 25: 252–267, doi: 10.1017/S0954422414000183.
  • Akkawi I, Zmerly H. Osteoporosis: current concepts. Joints 2018; 6(122): 122–127.
  • Awadalla P, Laberge C, Knoppers B, et al. Association of age-dependent height and bone mineral density decline with increased arterial stiffness and rate of fractures in hypertensive individuals. J Hypertens 2015; 33: 727–735, doi: 10.1097/HJH.0000000000000475.
  • Khosla S. Pathogenesis of age-related bone loss in humans. J Gerontol A Biol Sci Med Sci 2013; 68(10): 1226–1235, doi: 10.1093/gerona/gls163.
  • Arias CF, Herrero MA, Echeverri LF, et al. Bone remodeling: a tissue-level process emerging from cell-level molecular algorithms. PLoS ONE 2018; 13(9): 1–19.
  • National Resource Center. Osteoporosis: Peak Bone Mass in Women. Natl Institutes Heal Osteoporos Relat Bone Dis 2015; (June): 1–2.
  • Ministry of Health of the Republic of Indonesia. Data and conditions of osteoporosis in Indonesia. Infodatin: data and information center of the Ministry of Health of the Republic of Indonesia. 2015, p. 1–8. Available from URL:
  • Fornelli G, Isaia GC, Amelio PD. Ageing, muscle and bone. JGG 2016; 64: 75–80.
  • Laurent MR, Dedeyne L, Dupont J, et al. Age-related bone loss and sarcopenia in men. Maturitas 2019; 122: 51–56, doi: 10.1016/j.maturitas.2019.01.006.
  • Inderjeeth C, Preeti Nair A, Chan K, et al. Bone turnover markers in old vs early postmenopausal women. MOJ Gerontol Geriatr 2019;4(1): 22–26, doi: 10.15406/mojgg.2019.04.00171.
  • Jørgensen NR, Møllehave LT, Hansen YBL, et al. Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population. Osteoporos Int 2017; 28(7): 2103–2113, doi: 10.1007/s00198-017-4026-z.
  • Afsarimanesh N, Mukhopadhyay SC, Kruger M. Biosensors for the measurement of C-Terminal Telopeptide of Type I Collagen (CTX-I). JOsteoporos Phys Act 2017; 5(2): 1–6, doi: 10.4172/2329-9509.1000199.
  • Szulc P, Naylor K, Hoyle NR, et al. Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int 2017; 28: 2541–2556, doi:10.1007/s00198-017-4082-4.
  • Morris HA, Eastell R, Jorgesen NR, et al. Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin Chim Acta 2016; 467: 34–41, doi: 10.1016/j.cca.2016.06.036.
  • Chubb SAP. Measurement of C-terminal telopeptide of type I collagen (CTX) in serum. Clin Biochem 2012; 45(12): 928–935, doi: 10.1016/j.clinbiochem.2012.03.035.
  • Michelsen J, Wallaschofski H, Friedrich N, et al. Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone 2013; 57(2): 399–404, doi: 10.1016/j.bone.2013.09.010.
  • Drenjančević I, Cvetko ED. Influence of physical activity to bone metabolism. Med Glas 2013; 10(1): 12–19.
  • Ooi FK, Sahrir NA. Physical activity, bone remodelling and bone metabolism markers. J Exerc Sport Orthop 2018; 5(2): 1–4, doi: 10.15226/2374-6904/5/2/00171.
  • Strope MA, Nigh P, Carter MI, et al. Physical activity–associated bone loading during adolescence and young adulthood is positively associated with adult bone mineral density in men. Am J Men’s Health 2015; 9(6): 442–450, doi: 10.1177/1557988314549749.
  • Díaz Curiel M, Sierra Poyatos R. Bone cell response to physical activity. J Osteoporos Phys Act 2016; 4(3): 1–3, doi: 10.4172/2329-9509.1000184.
  • Alev A. Effects of aerobic exercise on bone-specific alkaline phosphatase and urinary ctx levels in premenopausal women. Turk J Phys Med Rehab 2013; 59: 310–313.
  • Rahim M, Ooi FK, Zuraida W, et al. Changes of bone metabolism markers and muscular performance with combined aerobic dance exercise and honey supplementation in adult women. Sport Exerc Med 2016; 1(6): 186–197, doi: 10.17140/SEMOJ-1-129.
  • Morseth B, Emaus N, Jørgensen L. Physical activity and bone: the importance of the various mechanical stimuli for bone mineral density. A review. Nor Epidemiol 2011; 20(2): 173–178.
  • Helge EW, Randers MB, Hornstrup T, et al. Street football is a feasible health-enhancing activity for homeless men: biochemical bone marker profile and balance improved. Scand J Med Sci Sport 2014; 24(Suppl. 1): 122–129, doi: 10.1111/sms.12244.
  • Eastell R, Szulc P. Osteoporosis 2: use of bone turnover markers in postmenopausal osteoporosis. Diabetes Endocrinol 2017; 8587(17):1–16, doi:
  • Hagman M, Wulff E, Hornstrup T, et al. Bone mineral density in lifelong trained male football players compared with young and elderly untrained men. J Sport Heal Sci 2018; 7(2): 159–168, doi: 10.1016/j.jshs.2017.09.009.
  • Szulc P, Umr I. Bone turnover: biology and assessment tools. Best Pract Res Clin Endocrinol Metab 2018; 32(5): 725–738, doi: 10.1016/j.beem.2018.05.003.
  • Cavalier E, Bergmann P, Bruyère O, et al. The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease:a consensus paper of the Belgian Bone Club. Osteoporos Int 2016; 27(4): 1–14, doi: 10.1007/s00198-016-3561-3
  • Eastell R, Pigott T, Gossiel F, et al. Bone turnover markers: are they clinically useful? Eur J Endocrinol 2018; 178(1): 19–31, doi:
  • Zaitseva OV, Shandrenko SG, Veliky MM. Biochemical markers of bone collagen type I metabolism. Ukr Biochem J 2015; 87(1): 21–32.
  • Shetty S, Kapoor N, Bondu JD, et al. Bone turnover markers: emerging tool in the management of osteoporosis. Indian J Endocr Metab 2016; 20: 846–522, doi: 10.4103/2230-8210.192914.
  • Greenblatt MB, Tsai JN, Wein MN. Review bone turnover markers in the diagnosis and monitoring of metabolic bone disease. Clin Chem 2017; 63(2): 464–474, doi: 10.1373/clinchem.2016.259085
  • UnitedHealthcare. Collagen Crosslinks and Biochemical Markers of Bone Turnover. Proprietary Information of UnitedHealthcare 2019:1–7. Available from URL:
  • Shetty S, Kapoor N, Bondu JD, et al. Bone turnover markers: emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 2016; 20(6): 846–852, doi: 10.4103/2230-8210.192914.
  • Park SY, Ahn SH, Yoo J, et al. Clinical application of bone turnover markers in osteoporosis in Korea. J Bone Metab 2019; 26(1): 19–22.
  • Hong AR, Kim SW. Effects of resistance exercise on bone health. Endocrinol Metab 2018; 33: 435–444.
  • Lee JH. The effect of long-distance running on bone strength and bone biochemical markers. J Exerc Rehabil 2019; 15(1): 26–30.
  • . Nagaraja MP, Jo H. The role of mechanical stimulation in recovery of bone loss-high versus low magnitude and frequency of force. Life 2014; 4: 117–130, doi: 10.3390/life4020117.
  • Leslie A, David NS, Michael AG, et al. The effect of calcium and vitamin D supplementation on bone health of male Jockeys. J Sci Med Sport 2016; 20(3): 225–229, doi: 10.1016/j.jsams.2016.08.004.
  • Chapurlat R, Marc J, Bernard J, et al. 2018 update of French recommendations on the management of postmenopausal osteoporosis. Joint Bone Spine 2018; 85(5): 519–530, doi: 10.1016/j.jbspin.2018.
  • National Osteoporosis Guideline Group. NOGG 2017: Clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2018: 1–36. Available from URL:
  • Sherk VD, Wherry SJ, Barry DW, et al. Calcium Supplementation attenuates disruptions in calcium homeostasis during exercise. Med Sci Sport Exerc 2018; 49(7): 1437–1442, doi: 10.1249/MSS.0000000000001239.
  • Barry DW1, Hansen KC, van Pelt RE, et al. Acute calcium ingestion attenuates exercise-induced disruption of calcium homeostasis. Med Sci Sport Exerc 2011: 617–623, doi: 10.1249/MSS.0b013e3181f79fa8.
  • Föger-Samwald U, Meinhart J, Skenderi K, et al. Changes in serum levels of myokines and wnt-antagonists after an ultramarathon race.PLoS ONE 2015; 10(7): 1–10, doi: 10.1371/journal.pone.0132478.
  • Gonzalez JT, Green BP, Rumbold PLS, et al. The influence of calcium supplementation on substrate metabolism during exercise in humans: a randomized controlled trial. Eur J Clin Nutr 2014; 68(6): 712–718, doi: 10.1038/ejcn.2014.41.
  • Shea KL, Barry DW, Sherk VD, et al. Calcium supplementation and parathyroid hormone response to vigorous walking in postmenopausal women. Med Sci Sport Exerc 2014; 46(10): 2007–2013, doi: 10.1249/MSS.0000000000000320.
  • ; Smith JK, Dykes R, Chi DS. The effect of long-term exercise on the production of osteoclastogenic and antiosteoclastogenic cytokines by
  • peripheral blood mononuclear cells and on serum markers of bone metabolism. J Osteoporos 2016; 4: 1–11, doi: 10.1155/2016/5925380.
  • Helge EW, Aagaard P, Jakobsen MD, et al. Recreational football training decreases risk factors for bone fractures in untrained premenopausal women. Scand J Med Sci Sport 2010; 20(Suppl. 1): 31–39, doi: 10.1111/j.1600-0838.2010.01107.x.
  • Gomez-Bruton A, Gonzalez-Aguero A, Gomez-Cabello A, et al. Is bone tissue really affected by swimming? A systematic review. PLoS ONE 2013; 8(8): 1–25, doi: 10.1371/journal.pone.0070119.
  • Taaffe DR, Robinson TL, Snow CM, et al. High-impact exercise promotes bone gain in well-trained female athletes. J Bone Miner Res 1997; 12(2): 255–260.
  • Helge EW, Andersen TR, Schmidt JF, et al. Recreational football improves bone mineral density and bone turnover marker profile in elderly men. Scand J Med Sci Sports 2014; 24: 98–104, doi: 10.1111/sms.12239.
  • Scott JPR, Sale C, Greeves JP, et al. The role of exercise intensity in the bone metabolic response to an acute bout of weight-bearing exercise. J Appl Physiol 2011; 110: 423–432 doi: 10.1152/japplphysiol.00764.2010.
  • Mohr M, Helge EW, Petersen LF, et al. Effects of soccer vs swim training on bone formation in sedentary middle-aged women. Eur J Appl Physiol 2015; 115(12): 2671–2679, doi: 10.1007/s00421-015-3231-8
  • Herrmann M, Mu M, Sand-hill M, et al. The effect of endurance exercise-induced lactacidosis on biochemical markers of bone turnover. Clin Chem Lab Med 2007; 45(10): 1381–1389, doi: 10.1515/CCLM.2007.282.
  • Welsh I, James MRI. The acute effects of exercise on bone turnover. Int J Sport Med 1997; 18(4): 247–251.
  • O’Kane JW, Hutchinson E, Atley LM, et al. Sport-related differences in biomarkers of bone resorption and cartilage degradation in endurance athletes. Osteoarthritis Cartilage 2006; 14(1): 71–76, doi: 10.1016/j.joca.2005.08.003.
  • Eliakim A, Raisz LG, Brasel JA, et al. Evidence for increased bone formation following a brief endurance-type training intervention in adolescent males. J Bone Miner Res 1997; 12(10): 1708–1713.
  • Woitge HW, Friedmann B, Suttner S, et al. Changes in bone turnover induced by aerobic and anaerobic exercise in young males. J Bone Miner Res 1998; 13(12): 1797–1804.
  • Kopeć A, Solarz K, Majda F, et al. An Evaluation of the levels of vitamin D and Bone turnover markers after the summer and winter periods in Polish professional soccer players. J Hum Kinet 2013; 38: 135–140, doi: 10.2478/hukin-2013-0053..
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.