• Non ci sono risultati.

vitamina D 3 (1,25vitD) (B) nel gruppo dei soggetti con IPP.

A

-2 0 2 4 6 8 10 12 14 16 DKK -1 1,3 1,4 1,5 1,6 1,7 1,8 1,9 2 2,1 2,2 Ca2+ DKK-1 = -2,283 + 5,609 * Ca2+; R^2 = ,077

B

2 4 6 8 10 12 14 16 DK K -1 0 10 20 30 40 50 60 70 80 90 100 1,25 VitD DKK-1 = 9,069 - ,034 * 1,25 VitD; R^2 = ,156 r = 0,278, p = 0,075 r = -0,395, p=0,085

75

Figura 19. Confronto tra i livelli sierici di β-catenina (β-C) nei due gruppi.

p=0,505

β-C (pg/ml)

76

Figura 20. Correlazione tra i livelli sierici di β-catenina (β-c) (pg/ml) e la BSP nel gruppo dei soggetti con IPP.

0 5 10 15 20 25 30 35 40 45 5 10 15 20 25 30 35 40 45 50 55 BALP r=0,511, p=0,035 β-c

77

Figura 21. Correlazione tra i livelli sierici di β-catenina (β-c) ed il T- (A) e Z- (B) score a livello del collo femorale (FNBMD).

0 5 10 15 20 25 30 35 40 45 -3,5 -3 -2,5 -2 -1,5 -1 -,5 0 T-FN ? catenin = 2,031 - 4,403 * T-FN; R^2 = ,221 0 5 10 15 20 25 30 35 40 45 -2,5 -2 -1,5 -1 -,5 0 ,5 1 Z-FN ? catenin = 6,359 - 4,643 * Z-FN; R^2 = ,233

A

B

β-c

β-c

r=-0,470 p=0,0657 r=-0,0483 p=0,0575

78

BIBLIOGRAFIA

1. Sundeep Khosla,1 Jennifer J. Westendorf,2 and Merry Jo Oursler1. Building bone to reverse osteoporosis and repair fractures. The Journal of Clinical Investigation. Volume 118 Number 2 February 2008

2. Bryan T. MacDonald1, Keiko Tamai2, and Xi He1 Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009 July ; 17(1): 9– 26

3. Peyman Bjorklund, Goran Åkerstrom, and Gunnar Westin Accumulation of Nonphosphorylated _-Catenin andc-myc in Primary and Uremic Secondary Hyperparathyroid Tumors. The Journal of Clinical Endocrinology & Metabolism 92(1):338–344. 2007.

4. Julian Heuberger and Walter Birchmeier.Interplay of Cadherin-Mediated Cell Adhesion and Canonical Wnt Signaling Cold Spring Harb Perspect Biol 2010

5. D.W. Dempster1,2, R. Müller3, H. Zhou1, T. Kohler3, E. Shane2, M. Parisien2, S.J. Silverberg2, and J.P. Bilezikian2Preserved Three- dimensional Cancellous Bone Structure in Mild Primary Hyperparathyroidism. Bone. 2007 July ; 41(1): 19–24.

6. Erming Tian, B.S., Fenghuang Zhan, Ph.D., Ronald Walker, M.D., Erik Rasmussen, M.S., Yupo Ma, M.D., Ph.D. et al. Role of the Wnt-Signaling Antagonist DKK1 in the Development of Osteolytic Lesions in Multiple Myeloma. NEJM 2003(349); 29.

79

7. Joseph J. Pinzone, Brett M. Hall, Nanda K. Thudi, Martin Vonau, Ya-Wei Qiang, Thomas J. Rosol John D. Shaughnessy Jr. The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood, 2009;(113): n°3.

8. Gill Holdsworth1, Patrick Slocombe1, Carl Doyle1, Bernadette Sweeney1, Vaclav Veverka4, 5, Kelly Le Riche1, Richard J. Franklin2, et al. Characterization of the interaction of sclerostin with the LRP family of Wnt co-receptors. JBC Papers in Press. Published on June 13, 2012 as Manuscript M112.350108.

9. Ulrike IL Mo¨ dder, Jackie A Clowes, Kelley Hoey, James M Peterson, Louise McCready, Merry Jo Oursler, B Lawrence Riggs, and Sundeep Khosla. Regulation of Circulating Sclerostin Levels by Sex Steroids in Women and in Men. JBMR, Vol. 26, No. 1, January 2011, pp 27–34

10. Ulrike I Mo¨ dder, Kelley A Hoey, Shreyasee Amin, Louise K McCready, Sara J Achenbach, B Lawrence Riggs, L Joseph Melton III, and Sundeep Khosla Relation of Age, Gender, and Bone Mass to Circulating Sclerostin Levels in Women and Men. JBMR Vol. 26, No. 2, February 2011, pp 373– 379.

11. Fei Liu, Sean Kohlmeier, and Cun-Yu Wang. Wnt Signaling and Skeletal Development. Cell Signal. 2008 June ; 20(6): 999–1009.

80

12. Yingzi Yang. Wnt signaling in development and disease.Cell & Bioscience 2012, 2:14.

13. Robling AG, Kedlaya R, Ellis SN, Childress PJ, Bidwell JP, Bellido T, Turner CH. Anabolic and catabolic regimens of human parathyroid hormone 1-34 elicit bone- and envelope-specific attenuation of skeletal effects in Sost- deficient mice..Endocrinology. 2011 Aug;152(8):2963-75.

14. Holdsworth G, Slocombe P, Doyle C, Sweeney B, Veverka V, Le Riche K, Franklin RJ, Compson J, Brookings D, Turner J, Kennedy J, Garlish R, Shi J, Newnham L, McMillan D, Muzylak M, Carr MD, Henry AJ, Ceska T, Robinson MK. Characterization of the interaction of sclerostin with the LRP family of Wnt co-receptors..J Biol Chem. 2012 Jun 13.

15. Voskaridou E, Christoulas D, Plata E, Bratengeier C, Anastasilakis A, Komninaka V, Kaliontzi D, Gkotzamanidou M, Polyzos SA, Dimopoulou M, Terpos E. High Circulating Sclerostin is Present in Patients with Thalassemia-associated Osteoporosis and Correlates with Bone Mineral Density. Horm Metab Res. 2012 May 11.

16. Yavropoulou MP, van Lierop AH, Hamdy NA, Rizzoli R, Papapoulos SE. Serum sclerostin levels in Paget's disease and prostate cancer with bone metastases with a wide range of bone turnover..Bone. 2012 Jul;51(1):153-7.

17. Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, Bouwmeester T, Schirle M, Bueno-Lozano M, Fuentes FJ, Itin PH, Boudin E, de Freitas F,

81

Jennes K, Brannetti B, Charara N, Ebersbach H, Geisse S, Lu CX, Bauer A, Van Hul W, Kneissel M.Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011 Jun 3;286(22):19489-500.

18. Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ, Bonewald LF, Kneissel M.Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol. 2010 Jun;30(12):3071-85.

19. Kramer I, Keller H, Leupin O, Kneissel M. Does osteocytic SOST suppression mediate PTH bone anabolism? Trends Endocrinol Metab. 2010 Apr;21(4):237-44.

20. Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH. Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol. 2011 Apr;6(4):877-82.

21. Onal M, Galli C, Fu Q, Xiong J, Weinstein RS, Manolagas SC, O'Brien CA. The RANKL distal control region is required for the increase in RANKL expression, but not the bone loss, associated with hyperparathyroidism or lactation in adult mice. Mol Endocrinol. 2012 Feb;26(2):341-8.

22. Yao GQ, Wu JJ, Troiano N, Insogna K. Targeted overexpression of Dkk1 in osteoblasts reduces bone mass but does not impair the anabolic response to intermittent PTH treatment in mice..J Bone Miner Metab. 2011 Mar;29(2):141-8.

82

23. Anastasilakis AD, Polyzos SA, Avramidis A, Toulis KA, Papatheodorou A, Terpos E. The effect of teriparatide on serum Dickkopf-1 levels in postmenopausal women with established osteoporosis..Clin Endocrinol (Oxf). 2010, Jun;72(6):752-7.

24. Cejka D, Jäger-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, Diarra D, Patsch JM, Kainberger F, Bohle B, Haas M. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients..Nephrol Dial Transplant. 2012 Jan;27(1):226- 30.

25. Butler JS, Murray DW, Hurson CJ, O'Brien J, Doran PP, O'Byrne JM.The role of Dkk1 in bone mass regulation: correlating serum Dkk1 expression with bone mineral density. J Orthop Res. 2011 Mar;29(3):414-8.

26. Silva BC, Costa AG, Cusano NE, Kousteni S, Bilezikian JP Catabolic and anabolic actions of parathyroid hormone on the skeleton..J Endocrinol Invest. 2011 Nov;34(10):801-10.

27. Costa AG, Cremers S, Rubin MR, McMahon DJ, Sliney J Jr, Lazaretti-Castro M, Silverberg SJ, Bilezikian JP. Circulating sclerostin in disorders of parathyroid gland function.. J Clin Endocrinol Metab. 2011 Dec;96(12):3804-10.

83

28. Costa AG, Bilezikian JP. Sclerostin: therapeutic horizons based upon its actions..Curr Osteoporos Rep. 2012 Mar;10(1):64-72.

29. Lombardi G, Di Somma C, Rubino M, Faggiano A, Vuolo L, Guerra E, Contaldi P, Savastano S, Colao A.J The roles of parathyroid hormone in bone remodeling: prospects for novel therapeutics. Endocrinol Invest. 2011 Jul;34(7 Suppl):18-22.

30. Aslan D, Andersen MD, Gede LB, de Franca TK, Jørgensen SR, Schwarz P, Jørgensen NR. Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans..Scand J Clin Lab Invest. 2012 Feb;72(1):14-22.

31. van Lierop AH, Witteveen JE, Hamdy NA, Papapoulos SE. Patients with primary hyperparathyroidism have lower circulating sclerostin levels than euparathyroid controls..Eur J Endocrinol. 2010 Nov;163(5):833-7.

32. 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 novel mechanism for hormonal control of osteoblastogenesis. Endocrinology. 2005 Nov;146(11):4577-83.

33. Cejka D, Jäger-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, Diarra D, Patsch JM, Kainberger F, Bohle B, Haas M. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients..Nephrol Dial Transplant. 2012 Jan;27(1):226- 30.

84

34. Björklund P, Akerström G, Westin G.An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/beta-catenin signaling. PLoS Med. 2007 Nov 27;4(11).

35.

Björklund P, Svedlund J, Olsson AK, Akerström G, Westin G. The internally truncated LRP5 receptor presents a therapeutic target in breast cancer. PLoS One. 2009;4(1):e4243.

Documenti correlati