Osteoporosis is a chronic disease, for which effective drugs are available. These drugs have reduced the risk of osteoporosis-related fractures in robust trials of 3–5 years duration. There is no evidence of anti-fracture efficacy for treatments of longer duration. The consequences of stopping treatments are very different for the different molecules. Bisphosphonates can be safely discontinued after 3–5 years of treatment if there was optimal adherence and if patients are no longer osteoporotic. This discontinuation cannot be applied in patients with recent fractures or for other treatments. Safety of prolonged treatment is a huge concern which must be managed appropriately. The decision of a prolonged treatment is driven by the underlying risk of fracture. This risk must be assessed regularly in order to share with the patient the benefit-risk ratio of prolonged treatment.
KeywordsAtypical fractures Benefit-risk ratio Bisphosphonates Fractures Long-term treatments Osteoporosis Osteonecrosis of the jaw Stopping treatment
Conflicts of Interest
Christian Roux: research grants and/or honoraria from AMGEN, LILLY, MSD, NOVARTIS, PFIZER, ROCHE, SERVIER, and UCB. Karine Briot: research grants and/or honoraria from AMGEN, LILLY, MSD, NOVARTIS, PFIZER, ROCHE, and SERVIER.
- 6.Melton III LJ et al (2013) Long-term mortality following fractures at different skeletal sites: a population-based cohort study. Osteoporos Int 24:1689–1696Google Scholar
- 24.Pazianas M, Abrahamsen B, Wang Y, Russell RG (2012) Incidence of fractures of the femur, including subtrochanteric, up to 8 years since initiation of oral bisphosphonate therapy: a register-based cohort study using the US MarketScan claims databases. Osteoporos Int 23:2873–2884PubMedCrossRefGoogle Scholar
- 27.Greenspan SL, Emkey RD, Bone HG III et al (2002) 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 137:875–883PubMedCrossRefGoogle Scholar
- 31.Brown JP et al (2012) Discontinuation of denosumab and associated fracture incidence: analysis from the FREEDOM trial. J Bone Miner Res 746–752Google Scholar
- 34.Cosman F, Caulin F, Eastell R, Boos N, Palermo L, Reid KR et al (2011) Who is at highest risk for new vertebral fractures after 3 years of annual zoledronic acid and who should remain on treatment? (internet). J Bone Miner Res; 26(suppl 1):Abstract 1248 cited 2012 Feb 12)Google Scholar
- 40.Sun K et al (2013) Bisphosphonate treatment and risk of esophageal cancer: a meta-analysis of observational studies. Osteoporos Int 24:279–286Google Scholar
- 42.Felsenberg D, Hoffmeister B, Amling M (2006) Bisphosphonattherapie assoziierte. Kiefernedrosen Deutsches Arzteblatt 46:A3078–A3080Google Scholar
- 45.Hellstein JW, Adler RA, Edwards B, Jacobsen PL, Kalmar JR, Koka S et al. Managing the care of patients receiving antiresorptive therapy for prevention and treatement of osteoporosis. Recommendations from the American Dental Association Council on Scientific Affairs. November 2011 (www.ada.org)
- 48.Beaudouin-Bazire Cet al (2013) Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis. Joint Bone Spine 80:201–205Google Scholar
- 51.Bone HG, Chapurlat R, Brandi ML, Brown JP, Czerwinski E, Krieg MA, et al. The effect of 3 or 6 years of denosumab exposure in women with postmenopausal osteoporosis: result from the FREEDOM extension. SubmittedGoogle Scholar
- 54.Bliuc D, Nguyen ND, Nguyen TV, Eisman JA, Center JR (2013) Compound risk of high mortality following osteoporotic fracture and re-fracture in elderly women and men. J Bone Miner Res 28:2317-2324Google Scholar
- 57.Jacques RM, Boonen S, Cosman F, Reid IR, Bauer DC, Black DM et al (2012) Relationship of changes in total hip bone mineral density to vertebral and non vertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5mg: the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 1627–1634Google Scholar