Panagiotis Anagnostis1, Stavroula A Paschou2, Gesthimani Mintziori2, Iuliana Ceausu3, Herman Depypere4, Irene Lambrinoudaki5, Alfred Mueck6, Faustino R Pérez-López7, Margaret Rees8, Levent M Senturk9, Tommaso Simoncini10, John C Stevenson11, Petra Stute12, Florence A Trémollieres13, Dimitrios G Goulis2. 1. Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece. Electronic address: anagnwstis.pan@yahoo.gr. 2. Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece. 3. Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, and Department of Obstetrics and Gynecology, 'Dr. I. Cantacuzino' Hospital, Bucharest, Romania. 4. Breast Clinic and Menopause Clinic, University Hospital, De Pintelaan 185, 9000 Gent, Belgium. 5. Second Department of Obstetrics and Gynecology, National and Kapodestrian University of Athens, Greece. 6. University Women's Hospital of Tuebingen,Calwer Street 7, 72076 Tuebingen, Germany. 7. Department of Obstetrics and Gynecology, Zaragoza University Faculty of Medicine, Lozano-Blesa University Hospital, Zaragoza 50009, Spain. 8. Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. 9. Istanbul University Cerrahpasa School of Medicine, Dept. of Obstetrics and Gynecology, Division of Reproductive Endocrinology, IVF Unit, Istanbul, Turkey. 10. Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100, Pisa, Italy. 11. National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London SW3 6NP, UK. 12. Department of Obstetrics and Gynecology, University Women's Hospital, Bern, Switzerland. 13. Menopause and Metabolic Bone Disease Unit, Hôpital Paule de Viguier, CHU Toulouse, Toulouse, France.
Abstract
BACKGROUND: Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and non-vertebral fractures, their optimal duration of use has not been determined. The occurrence of adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), has raised the issue of bisphosphonate or denosumab discontinuation ("drug holiday") after a certain treatment period. AIM: To assess the effect of bisphosphonate and denosumab discontinuation on fracture risk, as well as its possible benefits in reducing the risk of adverse effects. METHODS: Systematic review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Discontinuation of bisphosphonates should be considered in all patients who have beentreated for more than five years with alendronate, risedronate or zoledronic acid. In view of the limited evidence, no robust recommendations can be made for ibandronate and denosumab. If the patient has not experienced fractures before or during therapy and the fracture risk is low, a "drug holiday" canbe recommended. Although there is no solid evidence, 1-2 years for risedronate, 3-5 years for alendronate and 3-6 years for zoledronic acid are suggested. After this time, the patient should be reassessed. If a new fracture is experienced, or fracture risk has increased or BMD remains low (femoral neck T-score ≤-2.5), anti-osteoporotic treatment should be resumed. In the case of denosumab discontinuation, close monitoring is suggested, due to the possibility of rebound fractures.
BACKGROUND:Bisphosphonates and denosumab are used extensively in the treatment of postmenopausal osteoporosis. Despite their proven efficacy in the reduction of vertebral and non-vertebral fractures, their optimal duration of use has not been determined. The occurrence of adverse effects, such as osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF), has raised the issue of bisphosphonate or denosumab discontinuation ("drug holiday") after a certain treatment period. AIM: To assess the effect of bisphosphonate and denosumab discontinuation on fracture risk, as well as its possible benefits in reducing the risk of adverse effects. METHODS: Systematic review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Discontinuation of bisphosphonates should be considered in all patients who have beentreated for more than five years with alendronate, risedronate or zoledronic acid. In view of the limited evidence, no robust recommendations can be made for ibandronate and denosumab. If the patient has not experienced fractures before or during therapy and the fracture risk is low, a "drug holiday" canbe recommended. Although there is no solid evidence, 1-2 years for risedronate, 3-5 years for alendronate and 3-6 years for zoledronic acid are suggested. After this time, the patient should be reassessed. If a new fracture is experienced, or fracture risk has increased or BMD remains low (femoral neck T-score ≤-2.5), anti-osteoporotic treatment should be resumed. In the case of denosumab discontinuation, close monitoring is suggested, due to the possibility of rebound fractures.
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