Fracture prediction after discontinuation of 4 to 5 years of Alendronate therapy: The FLEX study

JAMA Internal Medicine

Volumn 174, Issue 7, 2014, Pages 1126-1134

  Bauer, Douglas C ^a   Schwartz, Ann ^a   Palermo, Lisa ^a   Cauley, Jane ^b   Hochberg, Marc ^c   Santora, Art ^d   Cummings, Steven R ^e   Black, Dennis M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^c UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^d MERCK RESEARCH LABORATORIES   (United States)

^e California Pacific Medical Research Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALENDRONIC ACID; ALKALINE PHOSPHATASE; AMINO TERMINAL TELOPEPTIDE; BIOCHEMICAL MARKER; BONE SPECIFIC ALKALINE PHOSPHATASE; CALCIUM; COLECALCIFEROL; COLLAGEN TYPE 1; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; ALKALINE PHOSPHATASE BLOOD LEVEL; ARTICLE; BONE TURNOVER; CONTROLLED STUDY; DIET SUPPLEMENTATION; DRUG WITHDRAWAL; DUAL ENERGY X RAY ABSORPTIOMETRY; FEMALE; FEMUR NECK FRACTURE; FOLLOW UP; FRACTURE; FRACTURE RISK; HIP FRACTURE; HUMAN; OSTEOLYSIS; POST HOC ANALYSIS; POSTMENOPAUSE; PREDICTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK; SPINE FRACTURE; VITAMIN SUPPLEMENTATION;

ABSORPTIOMETRY, PHOTON; AGED; AGED, 80 AND OVER; ALENDRONATE; ALKALINE PHOSPHATASE; BIOLOGICAL MARKERS; BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; FEMALE; FORECASTING; FRACTURES, BONE; HUMANS; MIDDLE AGED; PROSPECTIVE STUDIES; UNITED STATES;

EID: 84904116848     PISSN: 21686106     EISSN: None     Source Type: Journal    
DOI: 10.1001/jamainternmed.2014.1232     Document Type: Article

References (31)

1. Favus MJ. Bisphosphonates for osteoporosis. N Engl J Med. 2010;363(21):2027-2035.
2. Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010;95(4):1555-1565.
3. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. 2009;122(2)(suppl):S22-S32.
4. Barrett-Connor E, Swern AS, Hustad CM, et al. Alendronate and atrial fibrillation: ameta-analysis of randomized placebo-controlled clinical trials. Osteoporos Int. 2012;23(1):233-245.
5. Black DM, Schwartz AV, Ensrud KE, et al FLEX Research Group. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA. 2006;296(24):2927-2938. (Pubitemid 46021497)
6. Black DM, Cummings SR, Karpf DB, et al Fracture Intervention Trial Research Group. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet. 1996;348(9041):1535-1541. (Pubitemid 26411651)
7. Cummings SR, Black DM, Thompson DE, et al. 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(24):2077-2082. (Pubitemid 29014065)
8. Black DM, Reiss TF, Nevitt MC, Cauley J, Karpf D, Cummings SR. Design of the Fracture Intervention Trial. Osteoporos Int. 1993;3(suppl 3):S29-S39.
9. Ensrud KE, Barrett-Connor EL, Schwartz A, et al Fracture Intervention Trial Long-term Extension Research Group. Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension. J Bone Miner Res. 2004;19(8):1259-1269. (Pubitemid 41094366)
10. Looker AC, Wahner HW, Dunn WL, et al. Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int. 1998;8(5):468-489. (Pubitemid 28486716)
11. Garnero P, Delmas PD. Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease. J Clin Endocrinol Metab. 1993;77(4):1046-1053. (Pubitemid 23301484)
12. Rosen HN, Dresner-Pollak R, Moses AC, et al. Specificity of urinary excretion of cross-linked N-telopeptides of type I collagen as a marker of bone turnover. Calcif Tissue Int. 1994;54(1):26-29. (Pubitemid 24010512)
13. Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993;8(9):1137-1148. (Pubitemid 23261108)
14. Ivaska KK, Gerdhem P, Akesson K, Garnero P, Obrant KJ. Effect of fracture on bone turnover markers: a longitudinal study comparing marker levels before and after injury in 113 elderly women. J Bone Miner Res. 2007;22(8):1155-1164. (Pubitemid 351339697)
15. Eastell R, Vrijens B, Cahall DL, Ringe JD, Garnero P, Watts NB. Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J Bone Miner Res. 2011;26(7):1662-1669.
16. Black DM, Reid IR, Cauley JA, et al The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27(2):243-254.
17. Food and Drug Administration. Background Document for Meeting of Advisory Committee for Reproductive Health Drugs and Drug Safety and Risk Management Advisory Committee. http://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/ UCM270958.pdf. Published September 9, 2011. Accessed March 28, 2014.
18. Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis-where do we go from here? N Engl J Med. 2012;366(22):2048-2051.
19. Lewiecki EM. Bisphosphonates for the treatment of osteoporosis: insights for clinicians. Ther Adv Chronic Dis. 2010;1(3):115-128.
20. Boonen S, Ferrari S, Miller PD, et al. Postmenopausal osteoporosis treatment with antiresorptives: effects of discontinuation or long-term continuation on bone turnover and fracture risk - a perspective. J Bone Miner Res. 2012; 27(5):963-974.
21. McClung M, Harris ST, Miller PD, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am JMed. 2013;126(1):13-20.
22. Schwartz AV, Bauer DC, Cummings SR, et al FLEX Research Group. Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial. J Bone Miner Res. 2010;25(5):976-982.
23. McNabb BL, Vittinghoff E, Schwartz AV, et al. BMD changes and predictors of increased bone loss in postmenopausal women after a 5-year course of alendronate. J Bone Miner Res. 2013;28(6):1319-1327.
24. Qaseem A, Snow V, Shekelle P, Hopkins R Jr, Forciea MA, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149(6):404-415.
25. Bauer DC, Black DM, Garnero P, et al Fracture Intervention Trial Study Group. Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res. 2004;19(8):1250-1258. (Pubitemid 41094365)
26. Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res. 2003;18(6):1051-1056. (Pubitemid 37294942)
27. Delmas PD, Munoz F, Black DM, et al HORIZON-PFT Research Group. Effects of yearly zoledronic acid 5mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J Bone Miner Res. 2009;24(9):1544-1551.
28. Watts NB, Geusens P, Barton IP, Felsenberg D. Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in BMD. J Bone Miner Res. 2005;20(12):2097-2104. (Pubitemid 41698773)
29. Hochberg MC, Ross PD, Black D, et al Fracture Intervention Trial Research Group. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Arthritis Rheum. 1999;42(6):1246-1254. (Pubitemid 29268962)
30. Vasikaran S, Eastell R, Bruyère O, et al IOF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011;22(2):391-420.
31. Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis - for whom and for how long? N Engl J Med. 2012;366(22):2051-2053.