Abstract
The purpose of this study was to explore whether mechanical loading by exercise over a 1–year period in postmenopausal women had an effect on the receptor activator for nuclear factor kappa B ligand/osteoprotegerin (RANKL/OPG) system or the levels of the Wnt-signaling antagonist sclerostin. A total of 112 postmenopausal were randomized to either sedentary life (controls) or physical activity (training group). Ninety-two women fulfilled the study protocol. The training program consisted of three fast 30-min walks and one or two 1-h aerobic training sessions per week. The effect on the bone mineral density of the hip assessed with dual X-ray absorptiometry was positive as reported earlier. Blood samples were taken from participants at baseline and after 1 year and serum levels of OPG, RANKL and sclerostin were quantified together with the bone metabolism markers C-terminal telopeptide of collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results were analyzed using an analysis of covariance model using baseline values as the covariate. The training group displayed a clear mean increase of OPG +7.55 pg/ml compared to controls (p = 0.007). The mean changes for RANKL +0.19 pg/ml (square-root transformed data) and sclerostin +0.62 pmol/l were non-significant (p = 0.13 and p = 0.34). The changes in bone turnover markers CTX and BALP showed a tendency to decrease in the training group versus controls but the changes were small and non-significant. Although our study is limited in number of participating women, we have been able to show an OPG-associated, and RANKL- and sclerostin-independent, training-induced inhibition of postmenopausal bone loss.
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References
Prince RL, Draper C (2000) Bone and calcium. In: Lobo RA, Kelsey J, Marcus R (eds) Menopause. Academic Press, USA, pp 287–294
Lian JB, Stein GS (2001) Osteoblast biology. In: Marcus R, Feldman D, Kelsey J (eds) Osteoporosis. Academic Press, San Diego, pp 33–35
Kim CH, You L, Yellowley CE, Jacobs CR (2006) Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling. Bone 39:1043–1047
You L, Temiyasathit S, Lee P, Kim CH, Tummala P, Yao W, Kingery W, Malone AM, Kwon RY, Jacobs CR (2008) Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone 42:172–179
Vega D, Maalouf NM, Sakhaee K (2007) CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab 92:4514–4521
Garnero P (2009) Bone markers in osteoporosis. Curr Osteoporos Rep 7:84–90
Avbersek-Luznik I, Gmeiner Stopar T, Marc J (2007) Activity or mass concentration of bone-specific alkaline phosphatase as a marker of bone formation. Clin Chem Lab Med 45:1014–1018
Pacifici R (1996) Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11:1043–1051
Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, Holmes GB, Dunstan CR, DePaoli AM (2004) A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19:1059–1066
Samelson EJ, Broe KE, Demissie S, Beck TJ, Karasik D, Kathiresan S, Kiel DP (2008) Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip. J Clin Endocrinol Metab 93:1789–1795
Saunders MM, Taylor AF, Du C, Zhou Z, Pellegrini VD Jr, Donahue HJ (2006) Mechanical stimulation effects on functional end effectors in osteoblastic MG-63 cells. J Biomech 39:1419–1427
Mehrotra M, Saegusa M, Wadhwa S, Voznesensky O, Peterson D, Pilbeam C (2006) Fluid flow induces Rankl expression in primary murine calvarial osteoblasts. J Cell Biochem 98:1271–1283
Tang L, Lin Z, Li YM (2006) Effects of different magnitudes of mechanical strain on Osteoblasts in vitro. Biochem Biophys Res Commun 344:122–128
Kusumi A, Sakaki H, Kusumi T, Oda M, Narita K, Nakagawa H, Kubota K, Satoh H, Kimura H (2005) Regulation of synthesis of osteoprotegerin and soluble receptor activator of nuclear factor-kappaB ligand in normal human osteoblasts via the p38 mitogen-activated protein kinase pathway by the application of cyclic tensile strain. J Bone Miner Metab 23:373–381
West SL, Scheid JL, De Souza MJ (2009) The effect of exercise and estrogen on osteoprotegerin in premenopausal women. Bone 44:137–144
Ziegler S, Niessner A, Richter B, Wirth S, Billensteiner E, Woloszczuk W, Slany J, Geyer G (2005) Endurance running acutely raises plasma osteoprotegerin and lowers plasma receptor activator of nuclear factor kappa B ligand. Metabolism 54:935–938
Noble BS (2008) The osteocyte lineage. Arch Biochem Biophys 473:106–111
Piters E, Boudin E, Van Hul W (2008) Wnt signaling: a win for bone. Arch Biochem Biophys 473:112–116
Moustafa A, Sugiyama T, Saxon LK, Zaman G, Sunters A, Armstrong VJ, Javaheri B, Lanyon LE, Price JS (2009) The mouse fibula as a suitable bone for the study of functional adaptation to mechanical loading. Bone 44:930–935
Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283:5866–5875
Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Lindner B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiore CE. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab 95; 2248−2253
Bergstrom I, Landgren B, Brinck J, Freyschuss B (2008) Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density. Osteoporos Int 19:177–183
Bergstrom I, Lombardo C, Brinck J (2009) Physical training decreases waist circumference in postmenopausal borderline overweight women. Acta Obstet Gynecol Scand 88:308–313
Price JS, Sugiyama T, Galea GL, Meakin LB, Sunters A, Lanyon LE. Role of endocrine and paracrine factors in the adaptation of bone to mechanical loading. Curr Osteoporos Rep 9; 76−82
Bergstrom I, Freyschuss B, Landgren BM (2005) Physical training and hormone replacement therapy reduce the decrease in bone mineral density in perimenopausal women: a pilot study. Osteoporos Int 16:823–828
Reid IR (2008) Relationships between fat and bone. Osteoporos Int 19:595–606
Acknowledgments
We wish to thank Ingela Arvidsson and Lilian Larsson for excellent technical assistance. This study was supported by grants from the Stockholm County Council (ALF) and Swedish Research Council (VR-M K2009-52X-10363-17-3).
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G. Andersson and J. Brinck contributed equally to this work.
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Bergström, I., Parini, P., Gustafsson, S.A. et al. Physical training increases osteoprotegerin in postmenopausal women. J Bone Miner Metab 30, 202–207 (2012). https://doi.org/10.1007/s00774-011-0304-6
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DOI: https://doi.org/10.1007/s00774-011-0304-6