Abstract
Bone mass can be viewed as the net product of two counteracting metabolic processes, bone formation and bone resorption, which allow the skeleton to carry out its principal functions: mechanical support of the body, calcium dynamic deposition and haemopoiesis. Besides radiological methods, several blood and urinary molecules have been identified as markers of bone metabolic activity for estimating the rates and direction of the biological activities governing bone turnover. The advantages for the use of bone metabolism markers are that they are potentially less dangerous than radiological determinations, are more sensitive to changes in bone metabolism than radiological methods and are easily collected and analysed. The disadvantages are that they have high biological variability.
Physical exercise is a known source of bone turnover and is recommended for preventing osteoporosis and bone metabolism problems. There are numerous experiments on bone metabolism markers after acute exercise, but not after long-term training and during or after a whole competition season. Moreover, few studies on bone metabolism markers have evaluated their performance in elite and top-level athletes, who have a higher bone turnover than sedentary individuals.
Despite discrepant results among studies, most have shown that short exercise is insufficient for modifying serum concentrations of bone metabolism markers. Marker variations are more evident after several hours or days after exercise, bone formation markers are more sensitive than bone resorption markers, and stimulation of osteoblast and/or osteoclast functions is exercise dependent but the response is not immediate. The response depends on the type of exercise; the markers seem to be less sensitive to resistance exercise and the intensity of exercise is not discriminate. Comparisons between trained subjects and untrained controls have demonstrated the influence of exercise on bone turnover. During training, carboxy-terminal collagen cross-links (CTx), a bone resorption marker, was shown to be less sensitive than amino-terminal cross-linking telopeptide of type I collagen (NTx) and urinary pyridinolines, which were sensitive to anaerobic exercise. Whereas, the bone formation markers, bone alkaline phosphatase (BAP) and osteocalcin (OC) changed after 1 month and 2 months of an exercise programme, respectively. After 2 months, while BAP normalized, it was found to be sensitive to aerobic exercise and OC was found to be sensitive to anaerobic exercise.
After prolonged training and competition, bone formation markers are found to change in sedentary subjects enrolled in a physical activity programme. Professional athletes show changes in bone formation markers depending on programme intensity, whereas bone resorption appears to stabilize. Crucial for long-term training, are the characteristics of exercise (e.g. weight-bearing, impact).
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References
Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev 2005; 26: 97–122
Camozzi V, Tossi A, Simoni E, et al. Role of biochemical markers of bone remodelling in clinical practice. J Endocrinol Invest 2007; 30 Suppl.6: 13–7
Phan TC, Xu J, Zheng MH. Interaction between osteoblast and osteoclast: impact in bone disease. Histol Histopathol 2004; 19: 1325–44
Seibel MJ, Woitge HW. Basic principles and clinical applications of biochemical markers of bone metabolism. J Clin Densitom 1999; 2: 299–321
Panteghini M, Pagani F. Biological variation in bonederived biochemical markers in serum. Scand J Clin Lab Invest 1995; 55: 609–16
Panteghini M. Variabilita` analitica e biologica degli indicatori biochimici di rimodellamento osseo. Ligand Assay 1998; 3: 176–8
Delmas PD, Eastell R, Garnero P, et al. The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 2000; 11 Suppl.6: S2–17
Harris H. The human alkaline phosphatases: what we know and what we don’t know. Clin Chim Acta 1990; 186: 133–50
Magnusson P, Larsson L, Magnusson M, et al. Isoforms of bone alkaline phosphatase: characterisation and origin inhuman trabecular and cortical bone. J Bone Miner Res 1999; 14: 1926–33
Epstein S. Serum and urinary markers of bone remodeling: assessment of bone turnover. Endocr Rev 1988; 9: 437
Van Straalen JP, Sanders E, Prummel MF, et al. Bonealkaline phosphatase as indicator of bone formation. Clin Chim Acta 1991; 201: 27–33
Hauschka PV, Lian JB, Cole DE, et al. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 1989; 69: 990–1047
Poser JW, Esch FS, Ling NC, et al. Isolation and sequence of the vitamin K-dependent protein from human bone: undercarboxylationof the first glutamic acid residue. J Biol Chem 1980; 255: 8685–91
Brown JP, Delmas PD, Malaval L, et al. Serum bone Glaprotein: a specific marker for bone formation in postmenopausalosteoporosis. Lancet 1984; 1: 1091–3
Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metab 2008; 19: 161–6
Confavreux CB, Levine RL, Karsenty G. A paradigm of integrative physiology, the crosstalk between bone andenergy metabolisms. Mel Cell Endocrinol 2009; 310: 21–9
Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456–69
Takeda S, Karsenty G. Molecular bases of sympathetic regulation of bone mass. Bone 2008; 42: 837–40
Bell NH. Assays for osteocalcin: all are not equal. J Lab Clin Med 1997; 129: 396–7
Bjarnason NH, Christiansen C. Early response in biochemical markers predicts long-term response in bone massduring hormone replacement therapy in early postmenopausalwomen. Bone 2000; 26: 561–9
Hassager C, Jensen LT, Johansen JS, et al. The carboxyterminal propeptide of type 1 procollagen in serum as amarker of bone formation: the effect of nandrolone decanoateand female sex hormones. Metabolism 1991; 40: 205–8
Eriksen EF, Charles P, Meisen F, et al. Serum markers of type 1 collagen formation and degradation in metabolicbone disease: correlation with bone histomorphometry. J Bone Miner Res 1993; 8: 127–32
Eyre DR, Dickson IR, Van Ness KP. Collagen crosslinking in human bone and articular cartilage. Biochem J 1988; 252: 495–500
Garnero P, Gineyts E, Arbault P, et al. Different effects of bisphosphonate and estrogen therapy on free and peptideboundbone cross-links excretion. J Bone Miner Res 1995; 10: 641–9
Bonde M, Qvist P, Fledelius C, et al. Immunoassay for quantifying type I collagen degradation products in urineevaluated. Clin Chem 1994; 40: 2022–5
Risteli J, Niemi S, Elomaa I, et al. Bone resorption assay based on a peptide liberated during type I collagen degradation. J Bone Miner Res 1991; 6 Suppl.1: S251
Garnero P, Gineyts E, Riou JP, et al. Assessment of bone resorption with a new marker of collagen degradation inpatients with metabolic bone disease. J Clin Endocrinol Metab 1994; 79: 780–5
Cloos PAC, Fledelius C, Ovist P, et al. Biological clocks of bone aging: racemisation and isomerization, potential toolsto assess bone turnover [abstract]. Bone 1998; 23 Suppl.1: F440
Halleen JM, Alatalo SL, Suominen H, et al. Tartrateresistant acid phosphatase 5b: a novel serum marker ofbone resorption. J Bone Miner Res 2000; 15: 1337–45
Yaziji H, Janckila AJ, Lear SC, et al. Immunohistochemical detection of tartrate-resistant acid phosphatase in nonhematopoietichuman tissues. Am J Clin Pathol 1995; 104: 397–402
Halleen JM, Hentunen TA, Holmes SD. Osteoclast-derived tartrate-resistant acid phosphatase isoenzyme 5b as a serummarker of bone resorption rate [abstract]. Bone 1998; 23 Suppl.1: F432
Banfi G, Dolci A. Preanalytical phase of sport biochemistry and haematology. J Sports Med Phys Fitness 2003; 43: 223–30
Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989; 27: 409–37
Pettersson U, Nordstrom P, Lorentzon R. A comparison of bone mineral density and muscle strength in young maleadults with different exercise levels. Calcif Tissue Int 1999; 64: 490–8
Hannon R, Eastell R. Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 2000; 11 Suppl.6: S30–4
Shibata Y, Ohsawa I, Watanabe T, et al. Effects of physical training on bone mineral density and bone metabolism. J Physiol Anthropol Appl Human Sci 2003; 22: 203–8
Nishiyama S, Tomoeda S, Ohta T, et al. Differences in basal and postexercise osteocalcin levels in athletic and nonathletichumans. Calcif Tissue Int 1988; 49: 373–7
Malm H, Ronni-Sivula HM, Viinika LU, et al. Marathon running accompanied by transient decreases in urinarycalcium and serum osteocalcin levels. Calcif Tissue Int 1993; 52: 209–11
Kristoffersson A, Hultdin J, Holmlund I, et al. Effects of short-term maximal work on plasma calcium, parathyroidhormone, osteocalcin and biochemical markers of collagenmetabolism. Int J Sports Med 1995; 16: 145–9
Brahm H, Piehl-Aulin K, Ljunghall S. Biochemical markers of bone metabolism during distance running in healthy,regularly exercising men and women. Scand J Med Sci Sports 1996; 6: 26–30
Welsh L, Rutherford OM, James I, et al. The acute effects of exercise on bone turnover. Int J Sports Med 1997; 18: 247–51
Thorsen K, Kristoffersson A, Hultdin J, et al. Effects of moderate exercise on calcium, parathyroid hormone, andmarkers of bone metabolism in young women. Calcif Tissue Int 1997; 60: 16–20
Ashizawa N, Ouchi G, Fujimura R, et al. Effects of a single bout of resistance exercise on calcium and bone metabolismin untrained young males. Calcif Tissue Int 1998; 62: 104–8
Langberg H, Skovgaard D, Asp S, et al. Time pattern of exercise-induced changes in type I collagen turnover afterprolonged endurance exercise in humans. Calcif Tissue Int 2000; 67: 41–4
Rudberg A, Magnusson P, Larsson L, et al. Serum isoforms of bone alkaline phosphatase increase during physical exercisein women. Calcif Tissue Int 2000; 66: 342–7
Guillemant J, Accarie C, Peres G, et al. Acute effects of an oral calcium load on markers of bone metabolism duringendurance cycling exercise in male athletes. Calcif Tissue Int 2004; 74: 407–14
Gomez-Ambrosi J, Rodriguez A, Catalan V, et al. The boneadipose axis in obesity and weight loss. Obes Surg 2008; 18: 1134–43
Banfi G, Iorio EL, Corsi MM. Oxidative stress, free radicals, and bone remodelling. Clin Chem Lab Med 2008; 46: 1550–5
Whipple TJ, Le BH, Demers LM, et al. Acute effects of moderate intensity resistance exercise on bone cell activity. Int J Sports Med 2004; 25: 496–501
Herrmann M, Muller M, Scharhag J, et al. The effect of endurance exercise-induced lactacidosis on biochemicalmarkers of bone turnover. Clin Chem Lab Med 2007; 45: 1381–9
Mouzopoulos G, Stamatakos M, Tzurbakis M, et al. Changes of bone turnover markers after marathon runningover 245 km. Int J Sports Med 2007; 28: 576–9
Lippi G, Schena F, Schena F, et al. Acute variation of osteocalcin and parathyroid hormone in athletes afterrunning a half-marathon. Clin Chem 2008; 54: 1093–5
Pomerants T, Tillmann V, Tillmann V, et al. Impact of acute exercise on bone turnover and growth hormone/insulinlikegrowth factor axis in boys. J Sports Med Phys Fitness 2008; 48: 266–71
Salvesen H, Piehl-Aulin K, Ljunghall S. Changes in level of the carboxyterminal propeptide of type I procollagen: thecarboxyterminal cross-linked telopeptide of type I collagenand osteocalcin in response to exercise in well-trained menand women. Scand J Med Sci Sports Exerc 1994; 4: 186–90
Ratamess NA, Hoffman JR, Faigenbaum AD, et al. The combined effects of protein intake and resistance trainingon serum osteocalcin concentrations in strength and powerathletes. J Strength Cond Res 2007; 21: 1197–203
Eliakim A, Raisz LG, Brasel JA, et al. Evidence for increased bone formation following a brief endurance-typetraining intervention in adolescent males. J Bone Miner Res 1997; 12: 1708–13
Woitge HW, Friedmann B, Suttner S, et al. Changes in bone turnover induced by aerobic and anaerobic exercise inyoung males. J Bone Miner Res 1998; 13: 1797–804
Eliakim A, Brasel JA, Mohan S, et al. Physical fitness, endurance training, and the GH-IGF1 system in adolescentfemales. J Clin Endocrinol Metab 1996; 81: 3986–92
Maimoun L, Galy O, Manetta J, et al. Competitive season of triathlon does not alter bone metabolism and bone mineralstatus in male triathletes. Int J Sports Med 2004; 25: 230–4
Jürimä e, Purge P, Jürimä e, et al. Bone metabolism in elite male rowers: adaptation to Vol.-extended training. Eur J Appl Physiol 2006; 97: 127–32
McClanahan B, Ward KD, Vukadinovich C, et al. Bone mineral density in triathletes over a competitive season. J Sports Sci 2002; 20: 463–9
Beck BR, Doecke JD. Seasonal bone mass of college and senior female field hockey players. J Sports Med Phys Fitness 2005; 45: 347–54
Barry DW, Kohrt WM. BMD decreases over the course of a year in competitive male cyclists. J Bone Miner Res 2008; 23: 484–91
Rector RS, Rogers R, Ruebel M, et al. Participation in road cycling vs running is associated with lower bone mineraldensity in men. Metab Clin Exp 2008; 57: 226–32
Herrmann M, Herrmann W. The assessment of bone metabolism in female elite endurance athletes by biochemicalbone markers. Clin Chem Lab Med 2004; 42: 1384–9
Russell M, Stark J, Shriddha N, et al. Peptide YY in adolescent athletes with amenorrhea: eumenorrheic athletesand non-athletic controls. Bone 2009; 45: 104–9
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: 255–60
Bennell KL, Malcolm SA, Khan KM, et al. Bone mass and bone turnover in power athletes, endurance athletes, andcontrols: a 12-month longitudinal study. Bone 1997; 20: 477–84
Matsumoto T, Nakagawa S, Nishida S, et al. Bone density and bone metabolic markers in active collegiate athletes:findings in long-distance runners, judoists, and swimmers. Int J Sports Med 1997; 18: 408–12
Bemben DA, Buchanan TD, Bemben MG, et al. Influence of type of mechanical loading, menstrual status, and trainingseason on bone density in young women athletes. J Strength Cond Res 2004; 18: 220–6
O’Kane JW, Hutchinson E, Atley LM, et al. Sport-related differences in biomarkers of bone resorption and cartilagedegradation in endurance athletes. Osteoarthritis Cartil 2006; 14: 71–6
Morel J, Combe B, Francisco J, et al. Bone mineral density of 704 amateur sportsmen involved in different physicalactivities. Osteoporosis Int 2001; 12: 152–7
Creighton DL, Morgan AL, Boardley D, et al. Weight bearing exercise and markers of bone turnover in femaleathletes. J Appl Physiol 2001; 90: 565–70
Maimoun L, Mariano-Goulart D, Couret I, et al. Effects of physical activities that induce moderate external loading onbone metabolism in male athletes. J Sports Sci 2004; 22: 875–83
Maimoun L, Coste O, Puech AM. No negative impact of reduced leptin secretion on bone metabolism in male decathletes. Eur J Appl Physiol 2008; 102: 343–51
Ryan AS, Elahi D. Loss of bone mineral density in women athletes during aging. Calcif Tissue Int 1998; 63: 287–92
Karlsson KM, Karlsson C, Ahlborg HG, et al. The duration of exercise as a regulator of bone turnover. Calcif Tissue Int 2003; 73: 350–5
Acknowledgements
We are indebted to Mr Kenneth Britsch, who reviewed the manuscript for style. No funding was used in the preparation of this review. The authors have no conflicts of interest directly relevant to the content of the review.
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Banfi, G., Lombardi, G., Colombini, A. et al. Bone Metabolism Markers in Sports Medicine. Sports Med 40, 697–714 (2010). https://doi.org/10.2165/11533090-000000000-00000
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DOI: https://doi.org/10.2165/11533090-000000000-00000