46Hanna Styczyńska et al.similar, what suggests that OPG levels gradually increasedas gestational age progressed [18,23]. Thismay be related with the increasing level of estradiolfound during pregnancy. In postmenopausal womena significant, positive relationship between OPG <strong>and</strong>estradiol was found [24,25], but such a correlation wasnot confirmed in pregnant women [19]. Contrary to theothers [18,19] we found a weak positive correlationbetween OPG <strong>and</strong> OC but only at the 1 st trimester.We noticed a significant increase in OPG duringpregnancy. It is consistent with previous observationsin women [18,19]. Similarly to earlier findings [18],we observed much higher rise in OPG at the end of 3 rdtrimester with concomitant decline of serum calcium.Data on bone turnover markers during pregnancyare inconsistent. Among bone formation markers bonealkaline phosphatase was shown to rise with gestationalage [10,18,19] whereas osteocalcin did notchange or similarly to N-terminal propeptide of collagentype I showed a biphasic pattern with decreasefrom 1 st to second trimester, followed by increase inthe 3 rd [10,16,18]. We have measured biochemicalmarkers in fasting morning samples only twice, at 1 st<strong>and</strong> 3 rd trimester <strong>and</strong> observed the elevation in OCduring pregnancy, especially at 36-37 wks.Bone resorption, reflected by serum CTx, increasedsignificantly during pregnancy with peak levels at theend of 3 rd trimester that confirms data by other authors[5, 10, 11, 19]. This was accompanied by a decreasein serum calcium, especially before the delivery(36-37wks).Serum CTx <strong>and</strong> OPG seemed to be the only parametersto indicate elevated bone turnover. The nomogramproposed for the Polish premenopausalwomen indicated that serum CTx value over 0,490ng/ml <strong>and</strong> OC > 34 ng/ml (>95 th percentile) reflect theelevated bone turnover [26]. From our data it may beconcluded that, at least, increrased CTx during 1 sttrimester may be a good predictor for faster bone lossduring pregnancy.Our results confirm that serum OPG <strong>and</strong> bone turnovermarkers levels increase during pregnancy <strong>and</strong>clearly show that bone resorption precedes bone formation.In pregnancy many factors known to influence onthe bone mass undergo changes: increased calciumdem<strong>and</strong>, change in nutritional habits, changes in bodyweight <strong>and</strong> fat content, changed levels of physicalactivity <strong>and</strong> hormones with potential to affect bonemetabolism [27]. This may be the main reason fordifficulties in finding the exact role of OPG in relationto bone turnover during pregnancy. While the determinationof osteocalcin at the beginning of pregnancy,seems to be of limited clinical use, measuring OPG asa factor related to bone turnover or a bone resorptionmarker, such as CTx, may have a good predictive valuefor later pregnancy-associated bone loss or osteoporosis.This work was supported by grant BW 17/2002from The Nicolaus Copernicus University in Torun.CopernicusUniversity NICOLAUSCOPERNICUS UNIVERSITY NICOLAUSREFERENCES1. Tudor-Locke C, McColl RS. Factors related to variation inpremenopausal bone mineral status: a health promotionapproach. Osteoporos Int 2000; 11: 1-24.2. Stumpf UC, Kurth AA, Windolf J, Fassbender WJ. Pregnancy-associatedosteoporosis : an underestimated <strong>and</strong>underdiagnosed severe disease. A review of two cases inshort- <strong>and</strong> long-term follow-up. Adv Med Sci 2007; 52:94-97.3. Laktasic-Zerjavic N., Curkovic B., Babic-Naglic D., PotockiK., Prutki M., Soldo-Juresa D.: Transient osteoporosisof the hip in pregnancy. Successful treatment withcalcitonin. Z.Rheumatol 2007, 66, 510-34. Sowers M. Pregnancy <strong>and</strong> lactation as risk factors forsubsequent bone loss <strong>and</strong> osteoporosis. J Bone MinerRes1996; 11: 1052-1060.5. Yoon BK, Lee JW, Choi D, Roh CR, Lee JH. Changes inbone markers during pregnancy <strong>and</strong> puerperium. J KoreanMed Sci 2001; 15: 189-193.6. Kovacs C,Kronenberg M. Maternal-fetal calcium <strong>and</strong> bonemetabolism during pregnancy, puerperium, <strong>and</strong> lactation.Endocrine Rev 1997; 18(6): 832-837.7. Kent G, Price R, Gutteridge D, et al. Effect of pregnancy<strong>and</strong> lactation matrnal bone mass <strong>and</strong> calcium metabolism.Osteoporos Int 1993; Suppl. 1: 44-47.8. Ensom M, Liu P, Stephenson M. Effect of pregnancy onbone mineral density in healthy women. Obstet Gynecol2002;57(12): 99-111.9. Holmberg-Marttila D, Sievanen H, Tuimala R. Changes inbone mineral density during pregnancy <strong>and</strong> postpartum:prospective data on five women. Osteoporos Int 1999;10:41-46.10. Hellmeyer L, Ziller V, Anderer G, Ossendorf A, SchmidtS, Hadji P. Biochemical markers of bone turnover duringpregnancy : a longitudinal study. Exp Clin EndocrinolDiabetes 2006, 114:506-510.11. Black AJ, Topping J, Durham B, Farquharson RG, FraserWD. A detailed assessment of alterations in bone turnover,calcium homeostasis, <strong>and</strong> bone density in normalpregnancy. J Bone Miner Res 2000; 15(3): 557-563.12. Krieger I. Odrowąż-Sypniewska G. Osteoprotegeryna.Ortop Traumatol Rehab 2004; 6(1): 123-129.13.Philips TA, Ni J, Hunt JS. Death-inducing TNF superfamilylig<strong>and</strong>s <strong>and</strong> receptors are transcribed in human
Bone turnover during pregnancy 47placenta, cytotrophoblasts, placental macrophages <strong>and</strong>placental cell lines. Placenta 2002; 22: 663-672 .14. Hofbauer L, Heufelder A. Role of receptor activator ofnuclear factor-kappaB lig<strong>and</strong> <strong>and</strong> osteoprotegerin in bonecell biology. J Mol Med 2001; 79(5-6): 243-253.15. Naylor KE, Iqbal P, Fledelius C, Fraser RB, Eastell R.The effects of pregnancy on bone density <strong>and</strong> bone turnover.J Bone Miner Res 2000; 15: 129-137.16. Kaur M, Pearson D, Gogber I, et al. Longitudinal changesin bone mineral density during normal pregnancy. Bone2003; 32: 449-454.17. Di Gregorio S, Danilowicz K, Rubin Z, Mautalen C.Osteoporosis with vertebral fractures associated withpregnancy <strong>and</strong> lactation. Nutrition 2000; 12: 1052-1055.18. Uemura H, Yasui T, Kiyokawa M, et al. Serum osteoprotegerin//osteoclastogenesis –inhibitory factor duringpregnancy <strong>and</strong> lactation <strong>and</strong> their relationships with calciumregulating hormones <strong>and</strong> bone turnover markers. JEndocrinol 2002; 174: 353-359.19. Naylor K, Rogers A, Fraser R, et al. Serum osteoprotegerinas determinant of bone metabolism in a longitudinalstudy of human pregnancy <strong>and</strong> lactation. J Clin EndorinolMetab 2003; 88(11): 5361-5365.20. Fata J, Kong Y, Li Y, et al. The osteoclasts differentiationfactor osteoprotegerin-lig<strong>and</strong> is essential for mammarygl<strong>and</strong> development. Cell 2002; 103: 41-50.21. Theil L, Boyle W, Penninger J. T cells, bone loss <strong>and</strong>mammalian evolution. Annu Rev Immunol 2002; 20:795-823.22. Kanczler J, Bodamyali T, Millar T, et al. Human <strong>and</strong>bovine milk contains the osteoclastogenesis inhibitoryfactor, osteoprotegerin. J Bone Miner Res 2001; 16:1176.23. Hong I, Santalaya-Forgas I, Rouero R, et al. Maternalplasma osteoprotegerin contretration in normal pregnancy.Am J Obstet Gynecol 2005; 193(3 Pt 2): 1011-1015.24. Rogers A, Saleh G, Hannon R, et al. Circulating estradiol<strong>and</strong> osteoprotegerin as determinants of bone turnover <strong>and</strong>bone density in postmenopausal women. J Clin EndocrinolMetab 2002; 87: 4470-4475.25. Roger A, Eastell R, Circulating osteoprotegerin <strong>and</strong>receptor activator for nuclear factor kappaB lig<strong>and</strong>: clinicalutility in metabolic bone disease assessment. J ClinEndocrinol Metab 2005; 90(11): 6323-6331.26. Lukaszkiewicz J., Karczmarewicz E., Pludowski P.,Jaworski M., Czerwinski E., Lewinski A., Marcinowska-Suchowierska E., Milewicz A., Spaczynski M, LorencR.: Feasibility of simultaneous measurement of boneformation <strong>and</strong> bone resorption markers to assess boneturnover rate in postmenopausal women: An EPOLOSstudy. Med Sci Monit 2008, 14, PH65-7027. Karlsson M, Ahlborg H, Karlsson C, Pregnancy <strong>and</strong>lactation are not risk factors for osteoporosis <strong>and</strong> fractures.Lakartidningen 2005; 102(5): 290-293.Address for correspondence:Department of Laboratory MedicineNicolaus Copernicus University<strong>Collegium</strong> <strong>Medicum</strong>Sklodowskiej-Curie 985-094 BydgoszczPol<strong>and</strong>e-mail: kizdiagn@cm.umk.plReceived: 9.12.2008Accepted for publication: 16.01.2009
- Page 8: 8Wojciech J. Baranowskirating) move
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