Discontinuation of denosumab and associated fracture incidence: Analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) Trial

Journal of Bone and Mineral Research

Volumn 28, Issue 4, 2013, Pages 746-752

  Brown, Jacques P ^a   Roux, Christian ^b   Törring, Ove ^c   Ho, Pei Ran ^d   Beck Jensen, Jens Erik ^e   Gilchrist, Nigel ^f   Recknor, Christopher ^g   Austin, Matt ^d   Wang, Andrea ^d   Grauer, Andreas ^d   Wagman, Rachel B ^d  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c KAROLINSKA INSTITUTE   (Sweden)

^d AMGEN INC   (United States)

^e HVIDOVRE HOSPITAL   (Denmark)

^f Canterbury Geriatric Medical Research Trust   (New Zealand)

^g United Osteoporosis Centers   (United States)

Author keywords

Denosumab; discontinuation; fracture; off treatment; postmenopausal osteoporosis

Indexed keywords

AROMATASE INHIBITOR; BISPHOSPHONIC ACID DERIVATIVE; CALCITONIN; CALCIUM; CORTICOSTEROID DERIVATIVE; DENOSUMAB; PLACEBO; STRONTIUM RANELATE; VITAMIN D;

ADULT; AGED; ARTICLE; BONE DENSITOMETRY; BREAST CANCER; CONFIDENCE INTERVAL; CONTROLLED STUDY; DIET SUPPLEMENTATION; DRUG FATALITY; DRUG WITHDRAWAL; FEMALE; FRACTURE; HAZARD RATIO; HIP; HUMAN; INCIDENCE; LUMBAR SPINE; MAJOR CLINICAL STUDY; PATIENT COMPLIANCE; POSTMENOPAUSE OSTEOPOROSIS; CLINICAL TRIAL; COMPLICATION; DEMOGRAPHY; DOSE RESPONSE; MULTICENTER STUDY; OSTEOPOROSIS; OSTEOPOROTIC FRACTURES; RANDOMIZED CONTROLLED TRIAL; TREATMENT WITHDRAWAL;

AGED; DEMOGRAPHY; DENOSUMAB; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; INCIDENCE; OSTEOPOROSIS; OSTEOPOROTIC FRACTURES; WITHHOLDING TREATMENT;

EID: 84875313834     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.1808     Document Type: Article

References (31)

1. Greendale GA, Espeland M, Slone S, Marcus R, Barrett-Connor E., Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study. Arch Intern Med. 2002; 162: 665-72.
2. Neele SJ, Evertz R, De Valk-De Roo G, Roos JC, Netelenbos JC., Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women. Bone. 2002; 30: 599-603.
3. Tremollieres FA, Pouilles JM, Ribot C., Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women. Osteoporos Int. 2001; 12: 385-90.
4. Ettinger B, Grady D., The waning effect of postmenopausal estrogen therapy on osteoporosis. N Engl J Med. 1993; 329: 1192-3.
5. Felson DT, Zhang Y, Hannan MT, Kiel DP, Wilson PW, Anderson JJ., The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med. 1993; 329: 1141-6.
6. Thomsen K, Riis BJ, Johansen JS, Christiansen C, Rodbro P., Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy. Gynecol Endocrinol. 1987; 1: 169-75.
7. Ascott-Evans BH, Guanabens N, Kivinen S, Stuckey BG, Magaril CH, Vandormael K, Stych B, Melton ME., Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Arch Intern Med. 2003; 163: 789-94.
8. Gallagher JC, Rapuri PB, Haynatzki G, Detter JR., Effect of discontinuation of estrogen, calcitriol, and the combination of both on bone density and bone markers. J Clin Endocrinol Metab. 2002; 87: 4914-23.
9. Greenspan SL, Emkey RD, Bone HG, Weiss SR, Bell NH, Downs RW, McKeever C, Miller SS, Davidson M, Bolognese MA, Mulloy AL, Heyden N, Wu M, Kaur A, Lombardi A., Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002; 137: 875-83.
10. Sornay-Rendu E, Garnero P, Munoz F, Duboeuf F, Delmas PD., Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study. Bone. 2003; 33: 159-66.
11. Wasnich RD, Bagger YZ, Hosking DJ, McClung MR, Wu M, Mantz AM, Yates JJ, Ross PD, Alexandersen P, Ravn P, Christiansen C., Santora AC 2nd. Changes in bone density and turnover after alendronate or estrogen withdrawal. Menopause. 2004; 11: 622-30.
12. Schneider DL, Barrett-Connor EL, Morton DJ., Timing of postmenopausal estrogen for optimal bone mineral density. The Rancho Bernardo Study. JAMA. 1997; 277: 543-7.
13. Banks E, Beral V, Reeves G, Balkwill A, Barnes I., Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women. JAMA. 2004; 291: 2212-20.
14. Barrett-Connor E, Wehren LE, Siris ES, Miller P, Chen YT, Abbott TA 3rd, Berger ML, Santora AC, Sherwood LM., Recency and duration of postmenopausal hormone therapy: effects on bone mineral density and fracture risk in the National Osteoporosis Risk Assessment (NORA) study. Menopause. 2003; 10: 412-9.
15. Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES., Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004; 103: 440-6.
16. Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, Chlebowski RT, Gass M, LaCroix A, Manson JE, Prentice RL, Rossouw J, Stefanick ML., Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008; 299: 1036-45.
17. Lindsay R, Scheele WH, Neer R, Pohl G, Adami S, Mautalen C, Reginster JY, Stepan JJ, Myers SL, Mitlak BH., Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Intern Med. 2004; 164: 2024-30.
18. Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, Halse J, Lindsay R, Dalsky GP, Mitlak BH., Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res. 2005; 20: 1507-13.
19. Miller PD., Bisphosphonates: pharmacology and use in the treatment of osteoporosis In:, Marcus RFD, Nelson DA, Rosen CJ, editors. Osteoporosis, 3rd edition. Burlington, MA: Elsevier Academic Press; p. 1725-42. 2008.
20. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH., Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006; 38: 617-27.
21. Russell RG, Watts NB, Ebetino FH, Rogers MJ., Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008; 19: 733-59.
22. Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, Grauer A., Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int. 2008; 19: 365-72.
23. Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA, Satterfield S, Wallace RB, Bauer DC, Palermo L, Wehren LE, Lombardi A, Santora AC, Cummings SR., 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: 2927-38.
24. Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez R, Tan M, Ruzycky ME, Su G, Eastell R., 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: 243-54.
25. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C., Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361: 756-65.
26. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC., Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011; 96: 972-80.
27. Brown JP, Dempster DW, Ding B, Dent-Acosta R, San Martin J, Grauer A, Wagman RB, Zanchetta J., Bone remodeling in postmenopausal women who discontinued denosumab treatment: off-treatment biopsy study. J Bone Miner Res. 2011; 26: 2737-44.
28. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J., 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: 222-9.
29. Andersen PK, Gill RD., Cox's regression model for counting processes: a large sample study. Ann Stat. 1982; 10: 1100-20.
30. Prolia® (denosumab) prescribing information version 4 (May 2012) [Internet]. Thousand Oaks, CA, USA: Amgen Inc; 2012. [cited 2012 Nov 2]. Available from: http://pi.amgen.com/united-states/prolia/prolia-pi.pdf.
31. Prolia® (denosumab) summary of product characteristics [Internet]. Europe: Amgen Inc; 2010. [cited 2012 Nov 2]. Available from: http://ec.europa.eu/health/documents/community-register/2010/2010052679008/ anx-79008-en.pdf.