Bisphosphonate drug holidays – when, why and for how long?

References

• Watts NB, Bilezikian JP, Camacho PM, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract 2010;16(Suppl 3):1–37
   PubMedGoogle Scholar
• Khosla S, Bilezikian JP, Dempster DW, et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J Clin Endocrinol Metab 2012;97:2272–82
   PubMed Web of Science ®Google Scholar
• Jansen JP, Bergman GJ, Huels J, Olson M. The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis. Semin Arthritis Rheum 2011;40:275–84
   PubMed Web of Science ®Google Scholar
• Chen L, Wang G, Zheng F, Zhao H, Li H. Efficacy of bisphosphonates against osteoporosis in adult men: a meta-analysis of randomized controlled trials. Osteoporos Int 2015;26:2355–63
   PubMed Web of Science ®Google Scholar
• Kanis JA, Adams J, Borgström F, et al. The cost-effectiveness of alendronate in the management of osteoporosis. Bone 2008;42:4–15
   PubMed Web of Science ®Google Scholar
• Bolland MJ, Grey AB, Gamble GD, Reid IR. Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol Metab 2010;95:1174–81
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Miller PD, Bolognese MA, Lewiecki EM, 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;43:222–9
   PubMed Web of Science ®Google Scholar
• Greenspan SL, Emkey RD, Bone HG, 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;137:875–83
   PubMed Web of Science ®Google Scholar
• Khan AA, Morrison A, Hanley DA, et al.; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 2015;30:3–23
   PubMed Web of Science ®Google Scholar
• Khan AA, Sándor GK, Dore E, et al.; Canadian Association of Oral and Maxillofacial Surgeons. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 2008;35:1391–7
   PubMed Web of Science ®Google Scholar
• Goss AN. Bisphosphonate-associated osteonecrosis of the jaws. Climacteric 2007;10:5–8
   PubMed Web of Science ®Google Scholar
• Barasch A, Cunha-Cruz J, Curro FA, et al. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. J Dent Res 2011;90:439–44
   PubMed Web of Science ®Google Scholar
• Hoff AO, Toth BB, Altundag K, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 2008;23:826–36
   PubMed Web of Science ®Google Scholar
• Pazianas M, Miller P, Blumentals WA, Bernal M, Kothawala P. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther 2007;29:1548–58
   PubMed Web of Science ®Google Scholar
• Reid IR, Cornish J. Epidemiology and pathogenesis of osteonecrosis of the jaw. Nat Rev Rheumatol 2011;8:90–6
   PubMed Web of Science ®Google Scholar
• Hikita H, Miyazawa K, Tabuchi M, Kimura M, Goto S. Bisphosphonate administration prior to tooth extraction delays initial healing of the extraction socket in rats. J Bone Miner Metab 2009;27:663–72
   PubMed Web of Science ®Google Scholar
• Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: a second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014;29:1–23
   PubMed Web of Science ®Google Scholar
• Schilcher J, Michaëlsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011;364:1728–37
   PubMed Web of Science ®Google Scholar
• Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. J Bone Miner Res 2013;28:1729–37
   PubMed Web of Science ®Google Scholar
• Lee S, Yin RV, Hirpara H, et al. Increased risk for atypical fractures associated with bisphosphonate use. Fam Pract 2015;32:276–81
   PubMed Web of Science ®Google Scholar
• Meier RPH, Perneger TV, Stern R, Rizzoli R, Peter RE. Increasing occurrence of atypical femoral fractures associated with bisphosphonate use. Arch Intern Med 2012;172:930–6
   PubMed Web of Science ®Google Scholar
• Kwek EB, Koh JS, Howe TS. More on atypical fractures of the femoral diaphysis. N Engl J Med 2008;359:316–17
   PubMed Web of Science ®Google Scholar
• Goh SK, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br 2007;89:349–53
   PubMed Web of Science ®Google Scholar
• Rizzoli R, Akesson K, Bouxsein M, et al. Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report. Osteoporos Int 2011;22:373–90
   PubMed Web of Science ®Google Scholar
• 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;296:2927–38
   PubMed Web of Science ®Google Scholar
• 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;28:1319–27
   PubMed Web of Science ®Google Scholar
• 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;25:976–82
   PubMed Web of Science ®Google Scholar
• Black DM, Kelly MP, Genant HK, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur; Fracture Intervention Trial Steering Committee; HORIZON Pivotal Fracture Trial Steering Committee. N Engl J Med 2010;362:1761–71
   PubMed Web of Science ®Google Scholar
• 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;366:2051–3
   PubMed Web of Science ®Google Scholar
• Black DM, Reid IR, Boonen S, 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;27:243–54
   PubMed Web of Science ®Google Scholar
• Black DM, Reid IR, Cauley JA, et al. The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 2015;30:934–44
   PubMed Web of Science ®Google Scholar
• Watts NB, Chines A, Olszynski WP, et al. Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 2008;19:365–72
   PubMed Web of Science ®Google Scholar
• Eastell R, Hannon RA, Wenderoth D, Rodriguez-Moreno J, Sawicki A. Effect of stopping risedronate after long-term treatment on bone turnover. J Clin Endocrinol Metab 2011;96:3367–73
   PubMed Web of Science ®Google Scholar
• Frost ML, Siddique M, Blake GM, et al. Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women. Osteoporos Int 2012;23:2107–16
   PubMed Web of Science ®Google Scholar
• Bauer DC, Schwartz A, Palermo L, et al. Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study. JAMA Intern Med 2014;174:1126–34
   PubMed Web of Science ®Google Scholar
• Cosman F, Cauley JA, Eastell R, et al. Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J Clin Endocrinol Metab 2014;99:4546–54
   PubMed Web of Science ®Google Scholar
• McNabb B, Vittinghoff E, Eastell R, et al. A model of BMD changes after alendronate discontinuation to guide post alendronate BMD monitoring. J Clin Endocrinol Metab 2014;99:4094–100
   PubMed Web of Science ®Google Scholar
• Heiss G, Wallace R, Anderson GL, et al. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA 2008;299:1036–45
   PubMed Web of Science ®Google Scholar
• Bone HG, Bolognese MA, Yuen CK, 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;96:972–80
   PubMed Web of Science ®Google Scholar
• Fraser LA, Vogt KN, Adachi JD, Thabane L. Fracture risk associated with continuation versus discontinuation of bisphosphonates after 5 years of therapy in patients with primary osteoporosis: a systematic review and meta-analysis. Ther Clin Risk Manag 2011;7:157–66
   PubMed Web of Science ®Google Scholar
• Compston JE, Bilezikian JP. Bisphosphonate therapy for osteoporosis: the long and short of it. J Bone Miner Res 2012;27:240–2
   PubMed Web of Science ®Google Scholar
• Diab DL, Watts NB. Postmenopausal osteoporosis. Curr Opin Endocrinol Diabetes Obes 2013;20:501–9
   PubMed Web of Science ®Google Scholar
• Compston J, Bowring C, Cooper A, et al.; National Osteoporosis Guideline Group. Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update 2013. Maturitas 2013;75:392–6
   PubMed Web of Science ®Google Scholar