• 1
    Barons R, Rawadi G. Targeting the Wnt/β-catenin pathway to regulate bone formation in the adults skeleton. Endocrinology. 2007; 148: 263543.
  • 2
    Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006; 116: 12029.
  • 3
    Yavropoulou MP, Yovos JG. The role of the Wnt signaling pathway in osteoblast commitment and differentiation. Hormones (Athens). 2007; 6: 27994.
  • 4
    Clevers H. Wnt/β-catenin signaling in development and disease. Cell. 2006; 127: 46980.
  • 5
    Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol. 2007; 19: 37682.
  • 6
    Spencer GJ, Utting JC, Etheridge SL, Arnett TR, Genever PG. Wnt signaling in osteoblasts regulates expression of the receptor activator of NFκB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci. 2006; 119: 128396.
  • 7
    He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: arrows point the way. Development. 2004; 131: 166377.
  • 8
    Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005; 280: 2677075.
  • 9
    Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R. Bone density ligand, sclerostin, directly interacts with LRP5 but not LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2006; 21: 173849.
  • 10
    Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005; 280: 1988387.
  • 11
    Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001; 68: 57789.
  • 12
    Balemans W, Ebeling M, Patel N, van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, van Den Ende J, Willems PJ, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers G, Stratakis C, Lindpainter K, Vickery B, Foernzler D, van Hul W. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001; 10: 53743.
  • 13
    Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmely P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, Papapoulos S, Hamersma H, Brunkow ME. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002; 110: 14452.
  • 14
    Balemans W, Patel N, Ebeling M, van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, Verheij JB, Lindpaintner K, Vickery B, Foernzler D, van Hul W. Identification of a 52kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002; 39: 917.
  • 15
    Li X, Ominsky MS, Niu Q-T, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008; 23(6): 8609.
  • 16
    Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA. Osteocyte control of bone formation via sclerostin, a novel of BMP antagonist. EMBO J. 2003; 22: 626776.
  • 17
    Li X, Omnisky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shlhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C. Sclerostin antibody treatment increases bone formation, bone mass and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009; 24(4): 57888.
  • 18
    Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 2010; 25(5): 94859.
  • 19
    Ke HZ, Xiang JJ, Li X. “Inhibition of sclerostin by systemic treatment with a sclerostin monoclonal antibody enhances fracture healing in mice and rats,” in Proceedings of the 55th Annual Orthopedic Research Society Meeting, Las Vegas, USA, February 22–25, 2009.
  • 20
    Li X, Warmington K, Niu Q, Asuncion FJ, Barrero M, Xiz X, Grisauti M, Lee E, Wronski T, Ominsky MS, Simonet WS, Paszty C, Ke HZ. Increased bone formation and bone mass by sclerostin antibody was not blunted by pretreatment with alendronate in ovariectomized rats with established osteopenia. J Bone Miner Res. (Suppl 1), 2010: 580.
  • 21
    Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011; 26(1): 1926.
  • 22
    Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010; 95: 19917.
  • 23
    Modder UI, Hoey KA, Amin S, Mc Cready LK, Achenbach SJ, Riggs BL, Melton LJ III, Khosla S. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res. 2011; 26(2): 3739.
  • 24
    Gaudio A, Pennisi P, Bratengeier C, Torrisi V, Linder B, Mangiafico RA, Pulvirenti I, Hawa G, Tringali G, Fiorce CE. Increased sclerostin serum levels associated with bone formation and resorption markers in patients with immobilization-induced bone loss. J Clin Endocrinol Metab. 2010; 95: 224853.
  • 25
    Ardawi M-SM, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Radaddi RM. Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study. Bone. 2010; 47: 80414.
  • 26
    Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006; 81: 35373.
  • 27
    World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical Report Series. Geneva: WHO; 1994 No. 843.
  • 28
    Cleveland WS. Robust locally weighted regression and smoothing scatterplots. JA Stat Assoc. 1979; 74: 82936.
  • 29
    Glover SJ, Garnero P, Naylor K, Rogers A, Eastell R. Establishing a reference range for bone turnover markers in young, healthy women. Bone. 2008; 42: 62330.
  • 30
    van Bezooijen RL, Roelen BAJ, Visser A, van der Wee-pals L, de Wilt E, Karperien M, Hamersma H, Papapoulos SE, ten Dijke P, Loqwik CW. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004; 199: 80514.
  • 31
    van Bezooijen RL, ten-Dijke P, Papapoulos SE, Lowik CW. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev. 2005; 16: 31927.
  • 32
    Polyzos SA, Anastasilakis AD, Bratengeier C, Woloszczuk W, Papatheodorou A, Terpos E. Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women—the six-month effect of risedronate and teriparatide. Osteoporos Int. 2011; 10.1007/s00198-010-1525-6.
  • 33
    Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996; 11: 33749.
  • 34
    Overlie I, Morkrid L, Andersson AM, Skakebaek NE, Moen MH, Holte A. Inhibin A and B as markers of menopause: a five-year prospective longitudinal study of hormonal changes during the menopausal transition. Acta Obstet Gynecol Scand. 2005; 84: 2815.
  • 35
    Rico H, Arribas U, Casanova FJ, Duce AM, Hernandez ER, Cortes-Prieto J. Bone mass, bone metabolism, gonadal status and body mass index. Osteoporos Int. 2002; 13: 37987.
  • 36
    Reid IR. Relationships among body mass, its components and bone. Bone. 2002; 31: 54755.
  • 37
    Burger HG, Dudley EC, Hopper JL, Groome N, Guthrie JR, Green A, Dennerstein L. Prospectively measured levels of serum follicle-stimulating hormone, estradiol, and the dimeric inhibins during the menopausal transition in a population-based cohort of women. J Clin Endocrinol Metab. 1999; 84: 402530.
  • 38
    Melton LJ III, Looker AC, Shepherd JA, O'Connor MK, Achenbach SJ, Riggs BL, Khosla S. Osteoporosis assessment by whole body region vs. site-specific DXA. Osteoporos Int. 2005; 16: 155864.
  • 39
    Randolph JF Jr, Sowers M, Gold EB, Mohr BA, Luborsky J, Santoro N, McConnell DS, Finkelstein JS, Korenman SG, Matthews KA, Sternfeld B, Lasley BL. Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size and menopausal status. J Clin Endocrinol Metab. 2003; 88: 151622.
  • 40
    Wu X-Y, Wu X-P, Xie H, Zhang H, Peng Y-Q, Yuan L-Q, Su X, Luo X-H, Liao E-Y. Age-related changes in biochemical markers of bone turnover and gonadotropin levels and their relationship among Chinese adult women. Osteoporos Int. 2010; 21: 27585.
  • 41
    Vural F, Vural B, Yucesoy I, Badur S. Ovarian aging and bone metabolism in menstruating women aged 35–50 years. Maturitas. 2005; 52: 14753.
  • 42
    Iqbal J, Sun L, Kumar TR, Blair HC, Zaidi M. Follicle-stimulating hormone stimulates TNF production from immune cells to enhance osteoblasts and osteoclast formation. Proc Natl Acad Sci USA. 2006; 103: 1492530.
  • 43
    Zaidi M, Blair HC, Iqbal J, Zhu LL, Kumar TR, Zallone A, Sun L. Prospective actions of FSH and bone loss. Ann NY Acad Sci. 2007; 116: 37681.
  • 44
    Drake MT, McCready LK, Hoey KA, Atkinson EJ, Khosla S. Effects of suppression of follicle-stimulating hormone secretion on bone resorption markers in postmenopausal women. J Clin Endocrinol Metab. 2010; 95(11): 50638.
  • 45
    Modder UIL, Clowes JA, Hoey K, Peterson JM, McCready L, Oursler MJ, Riggs BL, Khosla S. Regulation of circulating sclerostin levels by sex steroids in women and men. J Bone Miner Res. 2011; 26(1): 2734.
  • 46
    Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, Manolagas SC, Jilka RL. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a noval mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005; 146: 457783.
  • 47
    O'Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, Robling AG, Bouxsein M, Schipani E, Turner CH, Jilka RL, Weinstein RS, Manolagas SC, Bellido T. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS ONE. 2008; 3: e2942.
  • 48
    van Lierop AH, Witteveen JE, Hamdy NAT, Papapoulos SE. Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls. Euro J Endocrinol. 2010; 163: 8337.
  • 49
    Drake MT, Srinivasan B, Modder UI, Peterson JM, McCready LK, Riggs BL, Dwyer D, Stolina M, Kostenuik D, Khosla S. Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women. J Bone Miner Res. 2010; 95(11): 505662.