J Korean Soc Endocrinol.  2006 Apr;21(2):91-100. 10.3803/jkes.2006.21.2.91.

New Approaches to the Diagnosis and Treatment of Postmenopausal Osteoporosis

• Kim B

• KMID: 1511947
• DOI: http://doi.org/10.3803/jkes.2006.21.2.91

Abstract

No abstract available.

MeSH Terms

Diagnosis*
Female
Humans
Osteoporosis, Postmenopausal*

Figure

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  Fig. 1. The risk of fracture in untreated post-menopausal women in relation to polymorphism in the MTHFR-gene. The fracture risk in the TT-group was significantly increased (P < 0.02). Data shown as fracture incidence per 1000 person years. Figure compiled from Abrahamsen et al.[12].

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  Fig. 2. Molecular mechanisms of the effect of estrogen on bone. Compiled from the review of Pheilschifter[14].

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  Fig. 3. The design of phase-III trials on strontium ranelate in post-menopausal osteoporosis (see the text for further explanation)[40,41].

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  Fig. 4. The effect of strontium ranelate on BMD of the lumbar spine. Data from the SOTI and TROPOS trials[40,41].

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  Fig. 5. The effect of strontium ranelate on the risk of vertebral fractures[40].

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  Fig. 6. The effect of strontium ranelate on the risk of hip fractures in a pre-defined high-risk group (age 75+ years and T-score below -3.0).

Reference

References

1. Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int. 2005; 16(Suppl 2):S3–S7.

2. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993; 94:646–650.

3. Nguyen TV, Blangero J, Eisman JA. Genetic epidemiological approaches to the search for osteoporosis genes. J Bone Miner Res. 2000; 15:392–401.

4. Peacock M, Koller DL, Fishburn T, Krishnan S, Lai D, Hui S, Johnston CC, Foroud T, Econs MJ. Sex-specific and non-sex-specific quantitative trait loci contribute to normal variation in bone mineral density in men. J Clin Endocrinol Metab. 2005; 90:3060–3066.

5. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S. Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 1987; 80:706–710.

6. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, Lacombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, B Steinmann, B Sullivan, A Superti-Furga, W Swoboda, MJ van den Boogaard, W Van Hul, M Vikkula, M Votruba, B Zabel, T Garcia, R Baron, BR Olsen, ML Warman. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001; 107:513–523.

7. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002; 346:1513–1521.

8. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, A Bawa, B Franklin, S McGuire, X Nogues, G Gong, KM Allen, A Anisowicz, AJ Morales, PT Lomedico, SM Recker, P Van Eerdewegh, RR Recker, ML Johnson. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002; 70:11–19.

9. L Van Wesenbeeck, E Cleiren, J Gram, RK Beals, O Benichou, D Scopelliti, L Key, T Renton, C Bartels, Y Gong, ML Warman, MC De Vernejoul, J Bollerslev, W Van Hul. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 2003; 72:763–771.

10. Bollerslev J, Wilson SG, Dick IM, Islam FM, Ueland T, Palmer L, Devine A, Prince RL. LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women. Bone. 2005; 36:599–606.

11. Brixen K, Nielsen TL, Wraae K, Bathum L, Andersen M, Abrahamsen B. A polymorphism in the gene coding for low-density lipoprotein receptor-related protein-5 (LRP5) is associated with peak bone mass in men - Results from the Odense Androgen Study. J Bone Miner Res. 2005; 20(Suppl 1):S233.

12. Abrahamsen B, Madsen JS, Tofteng CL, Stilgren L, Bladbjerg EM, Kristensen SR, Brixen K, Mosekilde L. A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. J Bone Miner Res. 2003; 18:723–729.

13. Abrahamsen B, Jorgensen HL, Nielsen TL, Andersen M, Haug E, Schwarz P, Hagen C, Brixen K. MTHFR c. 677C>T polymorphism as an independent predictor of peak bone mass in Danish men-results from the Odense Androgen Study. Bone. 2005; 38:215–219.

14. Pfeilschifter J. Role of cytokines in postmenopausal bone loss. Curr Osteoporos Rep. 2003; 1:53–58.

15. Hoidrup S, Prescott E, Sorensen TI, Gottschau A, Lauritzen JB, Schroll M, Gronbaek M. Tobacco smoking and risk of hip fracture in men and women. Int J Epidemiol. 2000; 29:253–259.

16. Vestergaard P, Mosekilde L. Fracture risk associated with smoking: a meta-analysis. J Intern Med. 2003; 254:572–583.

17. Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res. 2004; 19:370–378.

18. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005; 293:2257–2264.

19. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321–333.

20. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, S Wassertheil-Smoller. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004; 291:1701–1712.

21. Komulainen MH, Kroger H, Tuppurainen MT, Heikkinen AM, Alhava E, Honkanen R, Saarikoski S. HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial. Maturitas. 1998; 31:45–54.

22. Mosekilde L, Beck-Nielsen H, Sorensen OH, Nielsen SP, Charles P, Vestergaard P, Hermann AP, Gram J, Hansen TB, Abrahamsen B, Ebbesen EN, Stilgren L, Jensen LB, Brot C, Hansen B, Tofteng CL, Eiken P, Kolthoff N. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women-results of the Danish Osteoporosis Prevention Study. Maturitas. 2000; 36:181–193.

23. Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA. 2004; 291:47–53.

24. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 1999; 282:637–645.

25. Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, Secrest RJ, Cummings SR. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004; 96:1751–1761.

26. Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med. 1990. 322:p. 1265–1271.

27. Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC, Yanover MJ. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med. 1990; 323:73–79.

28. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996; 348:1535–1541.

29. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998; 280:2077–2082.

30. Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RWJ, Dequeker J, Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995; 333:1437–1443.

31. Pols HA, Felsenberg D, Hanley DA, Stepan J, Munoz-Torres M, Wilkin TJ, Qin-sheng G, Galich AM, Vandormael K, Yates AJ, Stych B. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Foxamax International Trial Study Group. Osteoporos Int. 1999; 9:461–468.

32. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001; 344:333–340.

33. Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000; 11:83–91.

34. Chesnut III CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004; 19:1241–1249.

35. McCloskey E, Selby P, Davies M, Robinson J, Francis RM, Adams J, Kayan K, Beneton M, Jalava T, Pylkkanen L, Kenraali J, Aropuu S, Kanis JA. Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study. J Bone Miner Res. 2004; 19:728–736.

36. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001; 344:1434–1441.

37. McClung MR, San MJ, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med. 2005; 165:1762–1768.

38. Marie PJ. Strontium ranelate: a novel mode of action of optimizing bone formation and resorption. Osteoporos Int. 2005; 16(suppl 1):S7–S10.

39. Ammann P. Strontium ranelate: A novel mode of action leading to renewed bone quality. Osteoporos Int. 2005; 16(Suppl 1):S11–S15.

40. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004; 350:459–468.

41. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Diaz CM, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ. Strontium ranelate reduces the risk of nonvertebral fractures in post-menopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab. 2005; 90:2816–2822.