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      Management of patients at very high risk of osteoporotic fractures through sequential treatments

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          Abstract

          Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an “anabolic first” approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.

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          Most cited references132

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          Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

          Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.
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            Osteoporosis in the European Union: medical management, epidemiology and economic burden

            Summary This report describes the epidemiology, burden, and treatment of osteoporosis in the 27 countries of the European Union (EU27). Introduction Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures which represent the main clinical consequence of the disease. Fragility fractures are associated with substantial pain and suffering, disability and even death for affected patients and substantial costs to society. The aim of this report was to characterize the burden of osteoporosis in the EU27 in 2010 and beyond. Methods The literature on fracture incidence and costs of fractures in the EU27 was reviewed and incorporated into a model estimating the clinical and economic burden of osteoporotic fractures in 2010. Results Twenty-two million women and 5.5 million men were estimated to have osteoporosis; and 3.5 million new fragility fractures were sustained, comprising 610,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures (i.e. fractures of the pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum and other femoral fractures). The economic burden of incident and prior fragility fractures was estimated at € 37 billion. Incident fractures represented 66 % of this cost, long-term fracture care 29 % and pharmacological prevention 5 %. Previous and incident fractures also accounted for 1,180,000 quality-adjusted life years lost during 2010. The costs are expected to increase by 25 % in 2025. The majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are untreated and the number of patients on treatment is declining. Conclusions In spite of the high social and economic cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by the aging populations, the use of pharmacological interventions to prevent fractures has decreased in recent years, suggesting that a change in healthcare policy is warranted.
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              European guidance for the diagnosis and management of osteoporosis in postmenopausal women

              Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting. Methods Systematic reviews were updated. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.
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                Author and article information

                Contributors
                cc@mrc.soton.ac.uk
                Journal
                Aging Clin Exp Res
                Aging Clin Exp Res
                Aging Clinical and Experimental Research
                Springer International Publishing (Cham )
                1594-0667
                1720-8319
                24 March 2022
                24 March 2022
                2022
                : 34
                : 4
                : 695-714
                Affiliations
                [1 ]GRID grid.5491.9, ISNI 0000 0004 1936 9297, MRC Lifecourse Epidemiology Centre, , University of Southampton, ; Southampton, UK
                [2 ]WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
                [3 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Department of Public Health, Epidemiology and Health Economics, , University of Liège, CHU Sart Tilman B23, ; 4000 Liège, Belgium
                [4 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Biochemistry Department, College of Science, , King Saud University, ; 11451 Riyadh, Kingdom of Saudi Arabia
                [5 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Division of Bone Diseases, Department of Medicine, Faculty of Medicine, , Geneva University Hospitals, University of Geneva, ; Geneva, Switzerland
                [6 ]F.I.R.M.O, Italian Foundation for the Research on Bone Diseases, Florence, Italy
                [7 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Department of Clinical Chemistry, , University of Liege, CHU de Liège, ; Liège, Belgium
                [8 ]Center of Bone Health, Frankfurt, Germany
                [9 ]GRID grid.10253.35, ISNI 0000 0004 1936 9756, Philipps-University of Marburg, ; Marburg, Germany
                [10 ]International Osteoporosis Foundation, Nyon, Switzerland
                [11 ]GRID grid.430506.4, ISNI 0000 0004 0465 4079, NIHR Southampton Biomedical Research Centre, , University of Southampton and University Hospital Southampton NHS Foundation Trust, ; Southampton, UK
                [12 ]GRID grid.5012.6, ISNI 0000 0001 0481 6099, Department of Health Services Research, , Care and Public Health Research Institute (CAPHRI), Maastricht University, ; Maastricht, The Netherlands
                [13 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, NDORMS, University of Oxford, ; Windmill Road, Oxford, UK
                [14 ]GRID grid.411958.0, ISNI 0000 0001 2194 1270, Mary McKillop Institute for Health Research, Australian Catholic University, ; Melbourne, Australia
                [15 ]GRID grid.11835.3e, ISNI 0000 0004 1936 9262, Centre for Metabolic Bone Diseases, , University of Sheffield Medical School, ; Beech Hill Road, Sheffield, UK
                [16 ]GRID grid.410566.0, ISNI 0000 0004 0626 3303, Department of Endocrinology, , Ghent University Hospital, ; Gent, Belgium
                [17 ]GRID grid.9851.5, ISNI 0000 0001 2165 4204, University of Lausanne, UNIL, CHUV, ; Lausanne, Switzerland
                [18 ]GRID grid.10822.39, ISNI 0000 0001 2149 743X, Faculty of Medicine, , University of Novi Sad, ; Novi Sad, Serbia
                [19 ]GRID grid.418664.9, ISNI 0000 0004 0586 9514, Clinical Center of Vojvodina, Clinic for Orthopedic Surgery, ; Novi Sad, Serbia
                [20 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Department of Internal Medicine, , Hospital del Mar-IMIM, Autonomous University of Barcelona and CIBERFES, Instituto Carlos III, ; Madrid, Spain
                [21 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Department of Diabetes, Nutrition and Metabolic Disorders, Clinical Pharmacology, , University of Liege, CHU de Liège, ; Liège, Belgium
                [22 ]GRID grid.9983.b, ISNI 0000 0001 2181 4263, Faculty of Medicine, , University of Lisboa, ; Lisbon, Portugal
                [23 ]GRID grid.412954.f, ISNI 0000 0004 1765 1491, Department of Rheumatology, , Hôpital Nord, CHU Saint-Etienne, ; Saint-Etienne, France
                [24 ]GRID grid.6279.a, ISNI 0000 0001 2158 1682, INSERM U1059, Université de Lyon, Université Jean Monnet, ; Saint-Etienne, France
                [25 ]GRID grid.410563.5, ISNI 0000 0004 0621 0092, Medical Faculty, Department of Pharmacology and Toxicology, , Medical University Sofia, ; Sofia, Bulgaria
                [26 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, NIHR Oxford Biomedical Research Centre, University of Oxford, ; Oxford, UK
                Author information
                https://orcid.org/0000-0002-5147-0550
                https://orcid.org/0000-0001-6290-752X
                https://orcid.org/0000-0001-5472-1725
                https://orcid.org/0000-0001-6174-1951
                https://orcid.org/0000-0002-8741-0592
                https://orcid.org/0000-0003-0947-2226
                https://orcid.org/0000-0003-4787-3151
                https://orcid.org/0000-0002-8194-2512
                https://orcid.org/0000-0003-4274-9258
                https://orcid.org/0000-0001-7985-0048
                https://orcid.org/0000-0002-3129-4326
                https://orcid.org/0000-0002-1400-6812
                https://orcid.org/0000-0002-4993-9399
                https://orcid.org/0000-0002-2866-8171
                https://orcid.org/0000-0001-5959-9183
                https://orcid.org/0000-0002-1537-422X
                http://orcid.org/0000-0003-3510-0709
                Article
                2100
                10.1007/s40520-022-02100-4
                9076733
                35332506
                78214dd5-b5b5-4fdd-8e1e-1cbb4cc8f587
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 February 2022
                : 18 February 2022
                Funding
                Funded by: no funding source
                Categories
                Review
                Custom metadata
                © Springer Nature Switzerland AG 2022

                osteoporosis,epidemiology,imminent,fracture,anabolic,antiresorptive

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