Recommendations on the management of fragility fracture risk in women younger than 70 years

Gynecological Endocrinology

Volumn 28, Issue 10, 2012, Pages 770-786

  Palacios, Santiago ^a   Christiansen, Claus ^b   Sánchez Borrego, Rafael ^c   Gambacciani, Marco ^d   Hadji, Payman ^e   Karsdal, Morten ^f   Lambrinoudaki, Irene ^g   Lello, Stefano ^g   O'beirne, Barbara ^f   Romao, Fatima ^h   Rozenberg, Serge ⁱ   Stevenson, John C ^j   Ben Rafael, Zion ^k  

^a Instituto Palacios de Salud Y Medicina de la Mujer   (Spain)

^b NORDIC BIOSCIENCE A S   (Denmark)

^c DIATROS Clínica de Atención a la Mujer   (Spain)

^d UNIVERSITY HOSPITAL OF PISA   (Italy)

^e UNIVERSITY HOSPITAL MARBURG   (Germany)

^f UNIVERSITY OF ATHENS   (Greece)

^g LABORATORIO DI PATOLOGIA VASCOLARE   (Italy)

^h SAINT PIERRE UNIVERSITY HOSPITAL   (Belgium)

ⁱ ROYAL BROMPTON HOSPITAL   (United Kingdom)

^j TEL AVIV UNIVERSITY   (Israel)

^k IVF Unit Department of OBGYN   (Israel)

more..

Author keywords

Detection and treatment; Recommendations; Risk of fragility fractures; Women younger than 70

Indexed keywords

25 HYDROXYVITAMIN D; AROMATASE INHIBITOR; BAZEDOXIFENE; BISPHOSPHONIC ACID DERIVATIVE; CALCITONIN; CALCIUM; CORTICOSTEROID; DENOSUMAB; ESTRADIOL RECEPTOR; ESTROGEN; IBANDRONIC ACID; PARATHYROID HORMONE; PARATHYROID HORMONE[1-34]; PLACEBO; PREDNISOLONE; RALOXIFENE; STRONTIUM RANELATE; TAMOXIFEN; TIBOLONE; VITAMIN D; ZOLEDRONIC ACID;

ARTICLE; BONE DENSITOMETRY; BONE DENSITY; BONE MASS; BONE REMODELING; BREAST CANCER; CLINICAL DECISION MAKING; DAIRY PRODUCT; ECHOGRAPHY; ENDOCRINE DISEASE; ENDOTHELIAL DYSFUNCTION; EVIDENCE BASED PRACTICE; FALLING; FAMILY HISTORY; FRAGILITY FRACTURE; HORMONE SUBSTITUTION; HUMAN; LIFESTYLE; LIVER DISEASE; LOW DRUG DOSE; MEDICAL HISTORY; METASTASIS; MORBIDITY; MORTALITY; MULTIPLE MYELOMA; OSSIFICATION; OSTEOLYSIS; OSTEOPOROSIS; PHYSICAL ACTIVITY; POSTMENOPAUSE; PRIORITY JOURNAL; RADIOGRAPHY; RESPIRATORY TRACT DISEASE; RISK ASSESSMENT; RISK FACTOR; SMOKING CESSATION; SUN EXPOSURE; TREATMENT DURATION; VERTEBRA FRACTURE; VITAMIN SUPPLEMENTATION;

AGED; ANTINEOPLASTIC AGENTS; BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; BREAST NEOPLASMS; ESTROGENS; EVIDENCE-BASED MEDICINE; FEMALE; HUMANS; MIDDLE AGED; OSTEOPOROSIS, POSTMENOPAUSAL; OSTEOPOROTIC FRACTURES; POSTMENOPAUSE; PRACTICE GUIDELINES AS TOPIC; RISK FACTORS; WORLD HEALTH;

EID: 84866431689     PISSN: 09513590     EISSN: 14730766     Source Type: Journal    
DOI: 10.3109/09513590.2012.679062     Document Type: Article

References (152)

1. Consensus Development Conference. Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1991; 90:107-110.
2. Ben Sedrine W, Radican L, Reginster JY. On conducting burden-ofosteoporosis studies: A review of the core concepts and practical issues. A study carried out under the auspices of a WHO Collaborating Center. Rheumatology (Oxford) 2001;40:7-14.
3. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-1733.
4. http://www.iofbonehealth.org/facts-and-statistics/references.html 5. Magaziner J, Lydick E, Hawkes W, Fox KM, Zimmerman SI, Epstein RS, Hebel Jr. Excess mortality attributable to hip fracture in white women aged 70 years and older. Am J Public Health 1997;87:1630-1636.
5. Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis? J Bone Miner Res 1992;7:1005-1010.
6. Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002;359:1929-1936.
7. Palacios S, Schez-Borrego R, Neyro JL, Quereda F, Vquez F, Pez M, Pez M. Knowledge and compliance from patients with postmenopausal osteoporosis treatment. Menopause Int 2009;15:113-119.
8. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center Jr. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009;301:513-521.
9. Leboime A, Confavreux CB, Mehsen N, Paccou J, David C, Roux C. Osteoporosis and mortality. Joint Bone Spine 2010;77 Suppl 2:S107-S112.
10. Kanis JA, Johnell O, Oden A, Borgstrom F, Zethraeus N, De Laet C, Jonsson B. The risk and burden of vertebral fractures in Sweden. Osteoporos Int 2004;15:20-26.
11. Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, Licata A, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001;285:320-323.
12. Briggs AM, Greig AM, Wark JD. The vertebral fracture cascade in osteoporosis: A review of aetiopathogenesis. Osteoporos Int 2007;18:575-584.
13. Kanis JA, Johnell O. Requirements for DXA for the management of osteoporosis in Europe. Osteoporos Int 2005;16:229-238.
14. Str O, Borgstrom F, Zethraeus N, Johnell O, Lidgren L, Ponzer S, Svensson O, et al. Long-term cost and effect on quality of life of osteoporosis-related fractures in Sweden. Acta Orthop 2008;79:269-280.
15. Heinrich S, Rapp K, Rissmann U, Becker C, Kig HH. Cost of falls in old age: A systematic review. Osteoporos Int 2010;21:891-902.
16. Landfeldt E, Lundkvist J, Str O. The societal burden of poor persistence to treatment of osteoporosis in Sweden. Bone 2011;48:380-388.
17. Lindsay R (1995) Estrogen deficiency. In: Riggs BL, Melton LJ III (eds.), Osteoporosis: Etiology, Diagnosis, and Management, 2nd edition. Philadelphia: Lippincott-Raven Publishers, pp. 133-160.
18. Compston JE. Osteoporosis. Clin Endocrinol (Oxf) 1990;33:653-682.
19. Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, Riggs BL. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 1988;241:84-86.
20. Vidal O, Kindblom LG, Ohlsson C. Expression and localization of estrogen receptor-beta in murine and human bone. J Bone Miner Res 1999;14:923-929.
21. Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M, Nakamaru Y, et al. Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med 1997;186:489-495.
22. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF. Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta. Nat Med 1996;2:1132-1136.
23. Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 2000;21:115-137.
24. Srivastava S, Toraldo G, Weitzmann MN, Cenci S, Ross FP, Pacifici R. Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. J Biol Chem 2001;276:8836-8840.
25. Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: Dissociation from transcriptional activity. Cell 2001;104:719-730.
26. Manolagas SC, Kousteni S, Jilka RL. Sex steroids and bone. Recent Prog Horm Res 2002;57:385-409.
27. Stevenson JC. Does estrogen therapy reduce coronary artery calcification in postmenopausal women? Nat Clin Pract Cardiovasc Med 2007;4:654-655.
28. Kanis JA, Johansson H, Oden A, Johnell O, De Laet C, Eisman JA, McCloskey EV, et al. A family history of fracture and fracture risk: A meta-analysis. Bone 2004;35:1029-1037.
29. van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM 2000;93:105-111.
30. Muscat Baron Y, Brincat MP, Galea R, Calleja N. Low intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures compared to hormone-treated and untreated postmenopausal women and premenopausal women without fractures. Climacteric 2007;10:314-319.
31. Wyshak G. Teenaged girls, carbonated beverage consumption, and bone fractures. Arch Pediatr Adolesc Med 2000;154:610-613.
32. De Laet C, Kanis JA, Od A, Johanson H, Johnell O, Delmas P, Eisman JA, et al. Body mass index as a predictor of fracture risk: A metaanalysis. Osteoporos Int 2005;16:1330-1338.
33. Berg KM, Kunins HV, Jackson JL, Nahvi S, Chaudhry A, Harris KA Jr, Malik R, Arnsten JH. Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med 2008;121:406-418.
34. Smith R. Idiopathic juvenile osteoporosis: Experience of twenty-one patients. Br J Rheumatol 1995;34:68-77.
35. Smith R, Stevenson JC, Winearls CG, Woods CG, Wordsworth BP. Osteoporosis of pregnancy. Lancet 1985;1:1178-1180.
36. Aebi S, Davidson T, Gruber G, Castiglione M; ESMO Guidelines Working Group. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21 Suppl 5:v9-14.
37. Guise TA. Bone loss and fracture risk associated with cancer therapy. Oncologist 2006;11:1121-1131.
38. Hadji P. Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol 2009;69:73-82.
39. Hadji P, Aapro MS, Body JJ, Bundred NJ, Brufsky A, Coleman RE, Gnant M, et al. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: Practical guidance for prevention and treatment. Ann Oncol 2011;22:2546-2555.
40. Reid DM, Doughty J, Eastell R, Heys SD, Howell A, McCloskey EV, Powles T, et al. Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK Expert Group. Cancer Treat Rev 2008;34 Suppl 1:S3-18.
41. NIH Consensus Development Panel. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285:785-795.
42. Kanis JA; on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary health-care level. Technical Report. University of Sheffield. UK: WHO Collaborating Centre, 2008.
43. Berry SD, Kiel DP, Donaldson MG, Cummings SR, Kanis JA, Johansson H, Samelson EJ. Application of the National Osteoporosis Foundation Guidelines to postmenopausal women and men: The Framingham Osteoporosis Study. Osteoporos Int 2010;21:53-60.
44. Cauley JA, El-Hajj Fuleihan G, Arabi A, Fujiwara S, Ragi-Eis S, Calderon A, Chionh SB, et al.; FRAX Position Conference Members. Official Positions for FRAX clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX. J Clin Densitom 2011;14:240-262.
45. Blake GM, Fogelman I. Role of dual-energy X-ray absorptiometry in the diagnosis and treatment of osteoporosis. J Clin Densitom 2007;10:102-110.
46. Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster JY, Borgstrom F, Rizzoli R; European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008;19:399-428.
47. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312:1254-1259.
48. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, et al. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 1993;341:72-75.
49. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical Report Series 843. Geneva: WHO, 1994
50. Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Lewiecki EM, Silverman S. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 2008;11:75-91.
51. Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 2000;85:231-236.
52. Sarkar S, Mitlak BH, Wong M, Stock JL, Black DM, Harper KD. Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy. J Bone Miner Res 2002;17:1-10.
53. Glr CC. Quantitative ultrasound techniques for the assessment of osteoporosis: Expert agreement on current status. The International Quantitative Ultrasound Consensus Group. J Bone Miner Res 1997;12:1280-1288.
54. Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS, Dooley KC, et al. Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 2009;42:929-942.
55. Delmas PD, Licata AA, Reginster JY, Crans GG, Chen P, Misurski DA, Wagman RB, Mitlak BH. Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover. Bone 2006;39:237-243.
56. Seibel MJ, Naganathan V, Barton I, Grauer A. Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal osteoporotic women treated with risedronate. J Bone Miner Res 2004;19:323-329.
57. Seibel MJ, Lang M, Geilenkeuser WJ. Interlaboratory variation of biochemical markers of bone turnover. Clin Chem 2001;47:1443-1450.
58. Clowes JA, Peel NF, Eastell R. The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: A randomized controlled trial. J Clin Endocrinol Metab 2004;89:1117-1123.
59. Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: The OFELY study. J Bone Miner Res 2007;22:425-433.
60. Garnero P, Dargent-Molina P, Hans D, Schott AM, Brrt G, Meunier PJ, Delmas PD. Do markers of bone resorption add to bone mineral density and ultrasonographic heel measurement for the prediction of hip fracture in elderly women? The EPIDOS prospective study. Osteoporos Int 1998;8:563-569.
61. Rosen CJ, Chesnut CH 3rd, Mallinak NJ. The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J Clin Endocrinol Metab 1997;82:1904-1910.
62. Chestnut CH 3rd, Bell N, Clark G, et al. Hormone replacement therapy in postmenopausal women; Urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med 1997; 102:29-37.
63. Christiansen C, Riis BJ, Rbro P. Prediction of rapid bone loss in postmenopausal women. Lancet 1987;1:1105-1108.
64. Cosman F, Nieves J, Wilkinson C, Schnering D, Shen V, Lindsay R. Bone density change and biochemical indices of skeletal turnover. Calcif Tissue Int 1996;58:236-243.
65. Chopin F, Hopp E, Morel G, Biver E, Borg S, Thomas T. Selecting the optimal treatment for glucocorticoid-induced osteoporosis. Joint Bone Spine 2011;78 Suppl 2:S218-S221.
66. Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 2011;49:1271-1274.
67. Palacios S, Castelo-Branco C, Cifuentes I, von Helde S, Bar L, Tapia-Ruano C, Mendez C, Rueda C. Changes in bone turnover markers after calcium-enriched milk supplementation in healthy postmenopausal women: A randomized, double-blind, prospective clinical trial. Menopause 2005;12:63-68.
68. Smith GI, Atherton P, Villareal DT, Frimel TN, Rankin D, Rennie MJ, Mittendorfer B. Differences in muscle protein synthesis and anabolic signaling in the postabsorptive state and in response to food in 65-80 year old men and women. PLoS ONE 2008;3:e1875.
69. Sinaki M, Brey RH, Hughes CA, Larson DR, Kaufman KR. Significant reduction in risk of falls and back pain in osteoporotic-kyphotic women through a Spinal Proprioceptive Extension Exercise Dynamic (SPEED) program. Mayo Clin Proc 2005;80:849-855.
70. Hackney ME, Kantorovich S, Levin R, Earhart GM. Effects of tango on functional mobility in Parkinson's disease: A preliminary study. J Neurol Phys Ther 2007;31:173-179.
71. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-281.
72. Zhang J, Chen F, Yun F, Chen J. Low level nicotine: A novel approach to reduce osteoporosis incidence. Med Hypotheses 2010;74:1067-1068.
73. Cummings-Vaughn LA, Gammack JK. Falls, osteoporosis, and hip fractures. Med Clin North Am 2011;95:495-506, x.
74. Robinovitch SN, Evans SL, Minns J, Laing AC, Kannus P, Cripton PA, Derler S, et al. Hip protectors: Recommendations for biomechanical testing - An international consensus statement (part I). Osteoporos Int 2009;20:1977-1988.
75. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: A meta-analysis. Lancet 2007;370:657-666.
76. Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: Evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 2007;92:1415-1423.
77. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, et al.; Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-683.
78. Quesada JM, Mata JM, Delgadillo J, et al. Low calcium intake and insufficient serum vitamin D status in treated and non-treated postmenopausal osteoporotic women in Spain. J Bone Miner Metab. 2007;22:S309.
79. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477-501.
80. Bukhari M. The National Osteoporosis Guideline Group's new guidelines: What is new? Rheumatology (Oxford) 2009;48:327-329.
81. Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010;17(1):25-54; quiz 55-6.
82. Palacios S. Bazedoxifene acetate for the management of postmenopausal osteoporosis. Drugs Today 2011;47:187-195.
83. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, et al.; Women's Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: The Women's Health Initiative randomized trial. JAMA 2003;290: 1729-1738.
84. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, et al.; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.
85. Banks E, Beral V, Reeves G, Balkwill A, Barnes I; Million Women Study Collaborators. Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women. JAMA 2004;291: 2212-2220.
86. Gallagher JC, Levine JP. Preventing osteoporosis in symptomatic postmenopausal women. Menopause 2011;18:109-118.
87. Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, Mol-Arts M, et al.; LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359: 697-708.
88. Archer DF, Hendrix S, Gallagher JC, Rymer J, Skouby S, Ferenczy A, den Hollander W, et al. Endometrial effects of tibolone. J Clin Endocrinol Metab 2007;92:911-918.
89. Bhuriya R, Singh M, Molnar J, Arora R, Khosla S. Bisphosphonate use in women and the risk of atrial fibrillation: A systematic review and meta-analysis. Int J Cardiol 2010;142:213-217.
90. Green J, Czanner G, Reeves G, Watson J, Wise L, Beral V. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: Case-control analysis within a UK primary care cohort. BMJ 2010;341:c4444.
91. Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA 2010;304: 657-663.
92. Papapoulos SE. Use of bisphosphonates in the management of postmenopausal osteoporosis. Ann N Y Acad Sci 2011;1218:15-32.
93. Schilcher J, Michasson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011;364:1728-1737.
94. Borgstr F, Str O, Coelho J, Johansson H, Oden A, McCloskey EV, Kanis JA. The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX. Osteoporos Int 2010;21:495-505.
95. Schousboe JT, Nyman JA, Kane RL, Ensrud KE. Cost-effectiveness of alendronate therapy for osteopenic postmenopausal women. Ann Intern Med 2005;142:734-741.
96. Chestnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin inpostmenopausal women with established osteoporosis: The Prevent Recurrence of Osteoporotic Fractures study. PROOF Study Group. Am J Med 2000;109:267-276.
97. Muz-Torres M, Alonso G, Raya MP. Calcitonin therapy in osteoporosis. Treat Endocrinol 2004;3:117-132.
98. .Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 1998;351:1451-1467.
99. Grey AB, Stapleton JP, Evans MC, Tatnell MA, Ames RW, Reid IR. The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women. Am J Med 1995;99:636-641.
100. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, et al. 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.
101. Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia A, Cummings S; Multiple Outcomes of Raloxifene Evaluation Investigators. Safety and adverse effects associated with raloxifene: Multiple outcomes of raloxifene evaluation. Obstet Gynecol 2004;104:837-844.
102. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, et al.; National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:2727-2741.
103. Miller PD, Chines AA, Christiansen C, et al. Effects of Bazedoxifene on BMD and bone turnover in postmenopausal women: 2 yr results of a randomized, double blind, placebo and active controlled study. J Bone Miner Res 2008, 23:525-535.
104. Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, Constantine GD, Chines AA. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: Results from a 3-year, randomized, placebo-, and activecontrolled clinical trial. J Bone Miner Res 2008;23:1923-1934.
105. Silverman SL, Chines AA, Kendler DL, Kung AW, Teglbjg CS, Felsenberg D, Mairon N, et al.; Bazedoxifene Study Group. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: Results of a 5-year, randomized, placebo-controlled study. Osteoporos Int 2012;23:351-363.
106. Christiansen C, Chesnut CH 3rd, Adachi JD, Brown JP, Fernandes CE, Kung AW, Palacios S, et al. Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled Phase 3 study of postmenopausal women with osteoporosis. BMC Musculoskelet Disord 2010;11:130.
107. Kharode Y, Bodine PV, Miller CP, Lyttle CR, Komm BS. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology 2008;149:6084-6091.
108. Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009;92:1045-1052.
109. Pinkerton JV, Gass ML, Dorin MH, et al. Evaluation of Bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009;92:1025-1038
110. Kagan R, Williams RS, Pan K, Mirkin S, Pickar JH. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause 2010;17:281-289.
111. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-342.
112. Delmas PD. Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases. J Clin Densitom 2008;11:325-338.
113. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J; Amg Bone Loss Study Group. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: A randomized blinded phase 2 clinical trial. Bone 2008;43:222-229.
114. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008;93:2149-2157.
115. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, et al.; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-765.
116. Neuprez A, Hiligsmann M, Scholtissen S, Bruyere O, Reginster JY. Strontium ranelate: The first agent of a new therapeutic class in osteoporosis. Adv Ther 2008;25:1235-1256.
117. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350:459-468.
118. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 2005;90:2816-2822.
119. Reginster JY, Felsenberg D, Boonen S, Diez-Perez A, Rizzoli R, Brandi ML, Spector TD, et al. Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: Results of a five-year, randomized, placebo-controlled trial. Arthritis Rheum 2008;58:1687-1695.
120. Reginster JY, Bruye O, Sawicki A, Roces-Varela A, Fardellone P, Roberts A, Devogelaer JP. Long-term treatment of postmenopausal osteoporosis with strontium ranelate: Results at 8 years. Bone 2009;45:1059-1064.
121. Reginster JY, Kaufman JM, Devogelaer JP, et al. Long-term efficacy and safety of strontium ranelate in postmenopausal osteoporotic women: Results over 10 years. Osteoporosis Int. 2011;22:S110-111.
122. Pernicova I, Middleton ET, Aye M. Rash, strontium ranelate and DRESS syndrome put into perspective. European Medicine Agency on the alert. Osteoporos Int 2008;19:1811-1812.
123. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, et al. 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.
124. Gallagher JC, Rosen CJ, Chen P, Misurski DA, Marcus R. Response rate of bone mineral density to teriparatide in postmenopausal women with osteoporosis. Bone 2006;39:1268-1275.
125. Geusens P, Sambrook P, Lems W. Fracture prevention in men. Nat Rev Rheumatol 2009;5:497-504.
126. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, et al.; PaTH Study Investigators. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 2005;353:555-565.
127. Greenspan SL, Bone HG, Ettinger MP, Hanley DA, Lindsay R, Zanchetta JR, Blosch CM, et al.; Treatment of Osteoporosis with Parathyroid Hormone Study Group. Effect of recombinant human parathyroid hormone (1-84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: A randomized trial. Ann Intern Med 2007;146:326-339.
128. Karsdal MA, Qvist P, Christiansen C, TankLB. Optimising antiresorptive therapies in postmenopausal women: Why do we need to give due consideration to the degree of suppression? Drugs 2006;66:1909-1918.
129. Karsdal MA, Qvist P, Christiansen C, et al. Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study. J Clin Endocrinol Metab. 1999; 84:2363-2368.
130. Karsdal MA, Martin TJ, Bollerslev J, Christiansen C, Henriksen K. Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res 2007;22:487-494.
131. Reszka AA, Rodan GA. Mechanism of action of bisphosphonates. Curr Osteoporos Rep 2003;1:45-52.
132. Rodan GA, Martin TJ. Therapeutic approaches to bone diseases. Science 2000;289:1508-1514.
133. Martin TJ, Seeman E. New mechanisms and targets in the treatment of bone fragility. Clin Sci 2007;112:77-91.
134. Bone HG, McClung MR, Roux C, Recker RR, Eisman JA, Verbruggen N, Hustad CM, et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: A two-year study in postmenopausal women with low bone density. J Bone Miner Res 2010;25:937-947.
135. Eisman JA, Bone HG, Hosking DJ, McClung MR, Reid IR, Rizzoli R, Resch H, et al. Odanacatib in the treatment of postmenopausal womenresolution of effect. J Bone Miner Res 2011;26:242-251.
136. Henriksen K, Bollerslev J, Everts V, Karsdal MA. Osteoclast activity and subtypes as a function of physiology and pathology-implications for future treatments of osteoporosis. Endocr Rev 2011;32:31-63.
137. Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, Holst JJ, Christiansen C. Disassociation of bone resorption and formation by GLP-2: A 14-day study in healthy postmenopausal women. Bone 2007;40:723-729.
138. Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, Holst JJ, Christiansen C. Four-month treatment with GLP-2 significantly increases hip BMD: A randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone 2009;45:833-842.
139. Henriksen DB, Alexandersen P, Byrjalsen I, Hartmann B, Bone HG, Christiansen C, Holst JJ. Reduction of nocturnal rise in bone resorption by subcutaneous GLP-2. Bone 2004;34:140-147.
140. Gottschalck IB, Jeppesen PB, Hartmann B, Holst JJ, Henriksen DB. Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and shortbowel syndrome. Scand J Gastroenterol 2008;43:1304-1310.
141. Gottschalck IB, Jeppesen PB, Holst JJ, Henriksen DB. Reduction in bone resorption by exogenous glucagon-like peptide-2 administration requires an intact gastrointestinal tract. Scand J Gastroenterol 2008;43:929-937.
142. Kornak U, Kasper D, Bl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, et al. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 2001;104:205-215.
143. Li YP, Chen W, Liang Y, Li E, Stashenko P. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nat Genet 1999;23:447-451.
144. Frattini A, Orchard PJ, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, et al. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet 2000;25:343-346.
145. Schaller S, Henriksen K, Sveigaard C, Heegaard AM, Hix N, Stahlhut M, Ovejero MC, et al. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation. J Bone Miner Res 2004;19:1144-1153.
146. Karsdal MA, Henriksen K, Sensen MG, Gram J, Schaller S, Dziegiel MH, Heegaard AM, et al. Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption. Am J Pathol 2005;166:467-476.
147. Visentin L, Dodds RA, Valente M, Misiano P, Bradbeer JN, Oneta S, Liang X, et al. A selective inhibitor of the osteoclastic V-H(+)-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats. J Clin Invest 2000;106:309-318.
148. Schaller S, Henriksen K, Sensen MG, Karsdal MA. The role of chloride channels in osteoclasts: ClC-7 as a target for osteoporosis treatment. Drug News Perspect 2005;18:489-495.
149. Brown EM. The calcium-sensing receptor: Physiology, pathophysiology and CaR-based therapeutics. Subcell Biochem 2007;45:139-167.
150. Horwitz MJ, Tedesco MB, Garcia-Oca A, Sereika SM, Prebehala L, Bisello A, Hollis BW, et al. Parathyroid hormone-related protein for the treatment of postmenopausal osteoporosis: Defining the maximal tolerable dose. J Clin Endocrinol Metab 2010;95:1279-1287.
151. Horwitz MJ, Tedesco MB, Gundberg C, Garcia-Ocana A, Stewart AF. Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2003;88:569-575.
152. Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebocontrolled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 2011;26:19-26.