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Licensed Unlicensed Requires Authentication Published by De Gruyter June 1, 2005

The assessment of bone metabolism in female elite endurance athletes by biochemical bone markers

  • Markus Herrmann and Wolfgang Herrmann

Abstract

Purpose: Premature osteoporosis is a frequent problem in female athletes. Current concepts suggest that a disruption of the hypothalamic-pituitary axis leads to hypoestrogenism, which then causes amenorrhea and osteoporosis. However, the underlying mechanisms have been insufficiently investigated. Osteoprotegerin (OPG) and soluble TNF-α receptor antagonist ligand (sRANKL) regulate the balance of osteoblasts and osteoclasts. Their role in the pathogenesis of osteoporosis in female athletes has not been studied yet.

Methods: We measured OPG and sRANKL in relation to biochemical bone markers [osteocalcin (OC), bone alkaline phosphatase (BAP), serum β-crosslaps (CTx)] and female sex hormones [estradiol (E2) and luteinizing hormone (LH)] in fastening blood samples from 25 female elite endurance athletes and 25 matched controls.

Results: Athletes exhibited significantly higher levels of the bone resorption marker CTx than controls (0.61±0.26 vs. 0.44±0.15ng/ml). OPG and sRANKL were not changed. Subgroup analysis revealed that athletes using oral contraceptives [A-OCC(−)] had significantly higher levels of CTx (0.82±0.20 vs. 0.50±0.14ng/ml), BAP [37.3 (23.2–54.4) U/l vs. 25.2 (20.3–35.6) U/l] and OPG (3.4±0.8 vs. 2.7±0.8ng/ml) than controls who did not use oral contraceptives [C-OCC(−)]. While the difference for CTx exceeded the least significant change in this marker by approximately 30%, the differences for the bone formation markers OC and BAP were close to the least significant change. In athletes using oral contraceptives [A-OCC(+)] we found no differences compared to controls.

Conclusions: A-OCC(−) athletes have increased bone turnover with a particular stimulation of bone resorption. The increased bone resorption is not accompanied by a shift of the OPG/sRANKL relationship towards an osteoclastogenic constellation. Since increased bone resorption was not detectable in A-OCC(+) athletes, it can be suggested that OCC use might protect bone health in female athletes.


Corresponding author: Prof. Dr. Wolfgang Herrmann, Department of Laboratory Medicine, University Hospital of Saarland, 66421 Homburg/Saar, Germany Phone: +49-6841-1623070, Fax: +49-6841-1623109,

References

1 Yeager KK, Agostini R, Nattiv A, Drinkwater B. The female athlete triad: disordered eating, amenorrhea, osteoporosis. Med Sci Sports Exerc 1993; 25:775–7.10.1249/00005768-199307000-00003Search in Google Scholar PubMed

2 Otis CL, Drinkwater B, Johnson M, Loucks A, Wilmore J. American College of Sports Medicine position stand. The Female Athlete Triad. Med Sci Sports Exerc 1997; 29:i–ix.10.1097/00005768-199705000-00037Search in Google Scholar PubMed

3 Golden NH. A review of the female athlete triad (amenorrhea, osteoporosis and disordered eating). Int J Adolesc Med Health 2002; 14:9–17.10.1515/IJAMH.2002.14.1.9Search in Google Scholar

4 Kazis K, Iglesias E. The female athlete triad. Adolesc Med 2003; 14:87–95.Search in Google Scholar

5 Warren MP, Perlroth NE. The effects of intense exercise on the female reproductive system. J Endocrinol 2001; 170:3–11.10.1677/joe.0.1700003Search in Google Scholar PubMed

6 Lindberg JS, Fears WB, Hunt MM, Powell MR, Boll D, Wade CE. Exercise-induced amenorrhea and bone density. Ann Intern Med 1984; 101:647–8.10.7326/0003-4819-101-5-647Search in Google Scholar PubMed

7 Lindberg JS, Powell MR, Hunt MM, Ducey DE, Wade CE. Increased vertebral bone mineral in response to reduced exercise in amenorrheic runners. West J Med 1987; 146:39–42.Search in Google Scholar

8 Marcus R, Cann C, Madvig P, Minkoff J, Goddard M, Bayer M, et al. Menstrual function and bone mass in elite women distance runners. Endocrine and metabolic features. Ann Intern Med 1985; 102:158–63.10.7326/0003-4819-102-2-158Search in Google Scholar PubMed

9 Pafumi C, Ciotta L, Farina M, Bosco P, Chiarenza M, Pernicone G, et al. Evaluation of bone mass in young amenorrheic women with anorexia nervosa. Minerva Ginecol 2002; 54:487–91.Search in Google Scholar

10 Drinkwater BL, Nilson K, Chesnut CH, III, Bremner WJ, Shainholtz S, Southworth MB. Bone mineral content of amenorrheic and eumenorrheic athletes. N Engl J Med 1984; 311:277–81.10.1056/NEJM198408023110501Search in Google Scholar PubMed

11 Drinkwater BL, Nilson K, Ott S, Chesnut CH, III. Bone mineral density after resumption of menses in amenorrheic athletes. J Am Med Assoc 1986; 256:380–2.10.1001/jama.1986.03380030082032Search in Google Scholar

12 Warren MP, Shantha S. The female athlete. Baillieres Best Pract Res Clin Endocrinol Metab 2000; 14:37–53.10.1053/beem.2000.0052Search in Google Scholar PubMed

13 Cann CE, Martin MC, Genant HK, Jaffe RB. Decreased spinal mineral content in amenorrheic women. J Am Med Assoc 1984; 251:626–9.10.1001/jama.1984.03340290040017Search in Google Scholar

14 Kopp-Woodroffe SA, Manore MM, Dueck CA, Skinner JS, Matt KS. Energy and nutrient status of amenorrheic athletes participating in a diet and exercise training intervention program. Int J Sport Nutr 1999; 9:70–88.10.1123/ijsn.9.1.70Search in Google Scholar PubMed

15 Lindsay R. Sex steroids in the pathogenesis and prevention of osteoporosis. In: Riggs BL, Melton, RJ, editors. Osteoporosis: etiology, diagnosis and management. New York: Raven Press, 1988:333–59.Search in Google Scholar

16 Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332:305–11.10.1056/NEJM199502023320506Search in Google Scholar PubMed

17 Holmberg-Marttila D, Leino A, Sievanen H. Bone turnover markers during lactation, postpartum amenorrhea and resumption of menses. Osteoporos Int 2003; 14:103–9.10.1007/s00198-002-1320-0Search in Google Scholar PubMed

18 Shapiro CL, Manola J, Leboff M. Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 2001; 19:3306–11.10.1200/JCO.2001.19.14.3306Search in Google Scholar PubMed

19 Weisinger JR, Gonzalez L, Alvarez H, Hernandez E, Carlini RG, Capriles F, et al. Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women. Kidney Int 2000; 58:331–5.10.1046/j.1523-1755.2000.00170.xSearch in Google Scholar PubMed

20 Bjarnason NH, Hassager C, Christiansen C. Postmenopausal bone remodelling and hormone replacement. Climacteric 1998; 1:72–9.10.3109/13697139809080684Search in Google Scholar PubMed

21 Garnero P, Delmas PD. New developments in biochemical markers for osteoporosis. Calcif Tissue Int 1996; 59(Suppl 1):S2–9.10.1007/s002239900168Search in Google Scholar PubMed

22 Okano H, Mizunuma H, Soda M, Matsui H, Aoki I, Honjo S, Ibuki Y. Effects of exercise and amenorrhea on bone mineral density in teenage runners. Endocr J 1995; 42:271–6.10.1507/endocrj.42.271Search in Google Scholar PubMed

23 Zanker CL, Swaine IL. Bone turnover in amenorrhoeic and eumenorrhoeic women distance runners. Scand J Med Sci Sports 1998; 8:20–6.Search in Google Scholar

24 Zanker CL, Swaine IL. Relation between bone turnover, oestradiol, and energy balance in women distance runners. Br J Sports Med 1998; 32:167–71.10.1136/bjsm.32.2.167Search in Google Scholar PubMed PubMed Central

25 Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology 2001; 142:5050–5.10.1210/endo.142.12.8536Search in Google Scholar PubMed

26 Chambers TJ. Regulation of the differentiation and function of osteoclasts. J Pathol 2000; 192:4–13.10.1002/1096-9896(2000)9999:9999<::AID-PATH645>3.0.CO;2-QSearch in Google Scholar

27 Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, et al. Osteoclast differentiationfactor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998; 95:3597–602.10.1073/pnas.95.7.3597Search in Google Scholar

28 Takahashi N, Udagawa N, Suda T. A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun 1999; 256:449–55.10.1006/bbrc.1999.0252Search in Google Scholar

29 Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 2002; 22:549–53.10.1161/01.ATV.0000012303.37971.DASearch in Google Scholar

30 Greydanus DE, Patel DR. The female athlete. Before and beyond puberty. Pediatr Clin North Am 2002; 49:553–80, vi.10.1016/S0031-3955(02)00005-6Search in Google Scholar

31 Hannon R, Blumsohn A, Naylor K, Eastell R. Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Miner Res 1998; 13:1124–33.10.1359/jbmr.1998.13.7.1124Search in Google Scholar

32 Castelo-Branco C, Vicente JJ, Pons F, Martinez de Osaba MJ, Casals E, Vanrell JA. Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives. J Reprod Med 2001; 46:875–9.Search in Google Scholar

33 Nappi C, Di Spiezio SA, Acunzo G, Bifulco G, Tommaselli GA, Guida M, Di Carlo C. Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception 2003; 67:355–9.10.1016/S0010-7824(03)00025-8Search in Google Scholar

34 Garnero P, Sornay-Rendu E, Delmas PD. Decreased bone turnover in oral contraceptive users. Bone 1995; 16:499–503.10.1016/8756-3282(95)00075-OSearch in Google Scholar

35 Grinspoon SK, Friedman AJ, Miller KK, Lippman J, Olson WH, Warren MP. Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea. J Clin Endocrinol Metab 2003; 88:3651–6.10.1210/jc.2003-030033Search in Google Scholar

36 Ryan AS, Elahi D. Loss of bone mineral density in women athletes during aging. Calcif Tissue Int 1998; 63:287–92.10.1007/s002239900528Search in Google Scholar

37 Christenson RH. Biochemical markers of bone metabolism: an overview. Clin Biochem 1997; 30:573–93.10.1016/S0009-9120(97)00113-6Search in Google Scholar

38 Chapurlat RD, Garnero P, Breart G, Meunier PJ, Delmas PD. Serum type I collagen breakdown product (serum CTX) predicts hip fracture risk in elderly women: the EPIDOS study. Bone 2000; 27:283–6.10.1016/S8756-3282(00)00325-2Search in Google Scholar

39 White CM, Hergenroeder AC. Amenorrhea, osteopenia, and the female athlete. Pediatr Clin North Am 1990; 37:1125–41.10.1016/S0031-3955(16)36978-4Search in Google Scholar

Received: 2004-7-15
Accepted: 2004-9-21
Published Online: 2005-6-1
Published in Print: 2004-12-1

©2004 by Walter de Gruyter Berlin New York

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