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Review Article| Volume 37, ISSUE 3, P323-336, August 2011

Duration of Treatment in Postmenopausal Osteoporosis: How Long to Treat and What are the Consequences of Cessation of Treatment?

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      References

        • Russell R.G.
        • Watts N.B.
        • Ebetino F.H.
        • et al.
        Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy.
        Osteoporos Int. 2008; 19: 733-759
        • Kennel K.A.
        • Drake M.T.
        Adverse effects of bisphosphonates: implications for osteoporosis management.
        Mayo Clin Proc. 2009; 84 ([quiz: 638]): 632-637
        • Nancollas G.H.
        • Tang R.
        • Phipps R.J.
        • et al.
        Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite.
        Bone. 2006; 38: 617-627
        • Seeman E.
        To stop or not to stop, that is the question.
        Osteoporos Int. 2009; 20: 187-195
        • Watts N.B.
        • Diab D.L.
        Long-term use of bisphosphonates in osteoporosis.
        J Clin Endocrinol Metab. 2010; 95: 1555-1565
        • Grey A.
        • Bolland M.
        • Wattie D.
        • et al.
        Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial.
        J Bone Miner Res. 2010; 25: 2251-2255
        • Bone H.G.
        • Hosking D.
        • Devogelaer J.P.
        • et al.
        Ten years’ experience with alendronate for osteoporosis in postmenopausal women.
        N Engl J Med. 2004; 350: 1189-1199
        • Black D.M.
        • Schwartz A.V.
        • Ensrud K.E.
        • et al.
        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: 2927-2938
        • Stock J.L.
        • Bell N.H.
        • Chesnut 3rd, C.H.
        • et al.
        Increments in bone mineral density of the lumbar spine and hip and suppression of bone turnover are maintained after discontinuation of alendronate in postmenopausal women.
        Am J Med. 1997; 103: 291-297
        • Rossini M.
        • Gatti D.
        • Zamberlan N.
        • et al.
        Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis.
        J Bone Miner Res. 1994; 9: 1833-1837
        • Greenspan S.L.
        • Emkey R.D.
        • Bone H.G.
        • et al.
        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: 875-883
        • Miller P.D.
        • Bolognese M.A.
        • Lewiecki E.M.
        • et al.
        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
        • Watts N.B.
        • Chines A.
        • Olszynski W.P.
        • et al.
        Fracture risk remains reduced one year after discontinuation of risedronate.
        Osteoporos Int. 2008; 19: 365-372
        • Black D.
        • Reid I.
        • Cauley J.
        • et al.
        The effect of 3 versus 6 years of zoledronic acid treatment in osteoporosis: a randomized extension to the HORIZON-pivotal fracture trial.
        J Bone Miner Res. 2010; 25 ([abstract:1070]): S22
        • Liberman U.A.
        • Weiss S.R.
        • Broll J.
        • et al.
        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
        • Tonino R.P.
        • Meunier P.J.
        • Emkey R.
        • et al.
        Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group.
        J Clin Endocrinol Metab. 2000; 85: 3109-3115
        • Harris S.T.
        • Watts N.B.
        • Genant H.K.
        • et al.
        Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.
        JAMA. 1999; 282: 1344-1352
        • Black D.M.
        • Delmas P.D.
        • Eastell R.
        • et al.
        Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.
        N Engl J Med. 2007; 356: 1809-1822
        • Lindsay R.
        • Miller P.
        • Pohl G.
        • et al.
        Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis.
        Osteoporos Int. 2009; 20: 943-948
        • Black D.
        • Reid I.
        • Cauley J.
        • et al.
        The effect of 3 versus 6 years of zolendronic acid treatment in osteoporosis: a randomized extension in the HORIZON-pivotal fracture trial (PFT).
        J Bone Miner Res. 2010;
        • Christiansen C.
        • Christensen M.S.
        • Transbol I.
        Bone mass after withdrawal of oestrogen replacement.
        Lancet. 1981; 1: 1053-1054
        • Christiansen C.
        • Christensen M.S.
        • Transbol I.
        Bone mass in postmenopausal women after withdrawal of oestrogen/gestagen replacement therapy.
        Lancet. 1981; 1: 459-461
        • Neele S.J.
        • Evertz R.
        • De Valk-De Roo G.
        • et al.
        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
        • Ettinger B.
        • Grady D.
        The waning effect of postmenopausal estrogen therapy on osteoporosis.
        N Engl J Med. 1993; 329: 1192-1193
        • Felson D.T.
        • Zhang Y.
        • Hannan M.T.
        • et al.
        The effect of postmenopausal estrogen therapy on bone density in elderly women.
        N Engl J Med. 1993; 329: 1141-1146
        • Tremollieres F.A.
        • Pouilles J.M.
        • Ribot C.
        Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women.
        Osteoporos Int. 2001; 12: 385-390
        • Naylor K.E.
        • Clowes J.A.
        • Finigan J.
        • et al.
        The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women.
        Bone. 2010; 46: 592-597
        • Bone H.G.
        • Bolognese M.A.
        • Yuen C.K.
        • et al.
        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: 972-980
        • Prince R.
        • Sipos A.
        • Hossain A.
        • et al.
        Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment.
        J Bone Miner Res. 2005; 20: 1507-1513
        • Lindsay R.
        • Scheele W.H.
        • Neer R.
        • et al.
        Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis.
        Arch Intern Med. 2004; 164: 2024-2030
        • Kaufman J.M.
        • Orwoll E.
        • Goemaere S.
        • et al.
        Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy.
        Osteoporos Int. 2005; 16: 510-516
        • Gallagher A.M.
        • Rietbrock S.
        • Olson M.
        • et al.
        Fracture outcomes related to persistence and compliance with oral bisphosphonates.
        J Bone Miner Res. 2008; 23: 1569-1575
        • Curtis J.R.
        • Westfall A.O.
        • Cheng H.
        • et al.
        Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday.
        Osteoporos Int. 2008; 19: 1613-1620
        • Park-Wyllie L.Y.
        • Mamdani M.M.
        • Juurlink D.N.
        • et al.
        Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women.
        JAMA. 2011; 305: 783-789
        • Schwartz A.V.
        • Bauer D.C.
        • Cummings S.R.
        • et al.
        Efficacy of continued alendronate for fractures in women with and without prevalent vertebral fracture: the FLEX trial.
        J Bone Miner Res. 2010; 25: 976-982
        • Shifren J.L.
        • Schiff I.
        Role of hormone therapy in the management of menopause.
        Obstet Gynecol. 2010; 115: 839-855
        • Rossouw J.E.
        • Anderson G.L.
        • Prentice R.L.
        • et al.
        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
        • Wasnich R.D.
        • Bagger Y.Z.
        • Hosking D.J.
        • et al.
        Changes in bone density and turnover after alendronate or estrogen withdrawal.
        Menopause. 2004; 11: 622-630
        • Ascott-Evans B.H.
        • Guanabens N.
        • Kivinen S.
        • et al.
        Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial.
        Arch Intern Med. 2003; 163: 789-794
        • Yates J.
        • Barrett-Connor E.
        • Barlas S.
        • et al.
        Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment.
        Obstet Gynecol. 2004; 103: 440-446
        • Martino S.
        • Disch D.
        • Dowsett S.A.
        • et al.
        Safety assessment of raloxifene over eight years in a clinical trial setting.
        Curr Med Res Opin. 2005; 21: 1441-1452
        • Olevsky O.M.
        • Martino S.
        Randomized clinical trials of raloxifene: reducing the risk of osteoporosis and breast cancer in postmenopausal women.
        Menopause. 2008; 15: 790-796
        • Briot K.
        • Tremollieres F.
        • Thomas T.
        • et al.
        How long should patients take medications for postmenopausal osteoporosis?.
        Joint Bone Spine. 2007; 74: 24-31
        • Cummings S.R.
        • San Martin J.
        • McClung M.R.
        • et al.
        Denosumab for prevention of fractures in postmenopausal women with osteoporosis.
        N Engl J Med. 2009; 361: 756-765
        • Miller P.D.
        • Wagman R.B.
        • Peacock M.
        • et al.
        Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial.
        J Clin Endocrinol Metab. 2011; 96: 394-402
        • Neer R.M.
        • Arnaud C.D.
        • Zanchetta J.R.
        • 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
        • Saag K.G.
        • Zanchetta J.R.
        • Devogelaer J.P.
        • et al.
        Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial.
        Arthritis Rheum. 2009; 60: 3346-3355
        • Schilcher J.
        • Aspenberg P.
        Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate.
        Acta Orthop. 2009; 80: 413-415
      1. Dell R, Greene D, Ott S, et al. A retrospective analysis of all atypical femur fractures seen in a large California HMO from the years 2007 to 2009. ASBMR Annual Meeting. Toronto, Canada, 2010. p. S61 [abstract: 1201].

        • Shane E.
        • Burr D.
        • Ebeling P.R.
        • et al.
        Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research.
        J Bone Miner Res. 2010; 25: 2267-2294
        • Black D.M.
        • Kelly M.P.
        • Genant H.K.
        • et al.
        Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur.
        N Engl J Med. 2010; 362: 1761-1771
        • Schilcher J.
        • Michaelsson K.
        • Aspenberg P.
        Bisphosphonate use and atypical fractures of the femoral shaft.
        N Engl J Med. 2011; 364: 1728-1737
        • Wang Z.
        • Bhattacharyya T.
        Trends in incidence of subtrochanteric fragility fractures and bisphosphonate use among the US elderly, 1996–2007.
        J Bone Miner Res. 2011; 26: 553-560
        • Peters E.
        • Hibbard J.
        • Slovic P.
        • et al.
        Numeracy skill and the communication, comprehension, and use of risk-benefit information.
        Health Aff (Millwood). 2007; 26: 741-748
        • Cohen J.T.
        • Neumann P.J.
        What’s more dangerous, your aspirin or your car? Thinking rationally about drug risks (and benefits).
        Health Aff (Millwood). 2007; 26: 636-646
        • Dobnig H.
        • Stepan J.J.
        • Burr D.B.
        • et al.
        Teriparatide reduces bone microdamage accumulation in postmenopausal women previously treated with alendronate.
        J Bone Miner Res. 2009; 24: 1998-2006
        • Stepan J.J.
        • Burr D.B.
        • Li J.
        • et al.
        Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis.
        Osteoporos Int. 2010; 21: 2027-2036
        • Misof B.M.
        • Paschalis E.P.
        • Blouin S.
        • et al.
        Effects of 1 year of daily teriparatide treatment on iliacal bone mineralization density distribution (BMDD) in postmenopausal osteoporotic women previously treated with alendronate or risedronate.
        J Bone Miner Res. 2010; 25: 2297-2303
        • Leslie W.D.
        • Morin S.
        • Lix L.M.
        A before-and-after study of fracture risk reporting and osteoporosis treatment initiation.
        Ann Intern Med. 2010; 153: 580-586
        • Davis S.R.
        • Kirby C.
        • Weekes A.
        • et al.
        Simplifying screening for osteoporosis in Australian primary care: the Prospective Screening for Osteoporosis; Australian Primary Care Evaluation of Clinical Tests (PROSPECT) study.
        Menopause. 2011; 18: 53-59
        • Sambrook P.
        Who will benefit from treatment with selective estrogen receptor modulators (SERMs)?.
        Best Pract Res Clin Rheumatol. 2005; 19: 975-981