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      Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

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          Abstract

          Introduction

          This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into 4 distinct themes:

          1. Case-finding and management of individuals at high risk of fracture

          2. Public awareness of osteoporosis and fragility fractures

          3. Reimbursement and health system policy

          4. Epidemiology of fracture in the developing world

          Methods

          Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all.

          Results

          Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case-finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health, and people who have diseases whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored.

          Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries, but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long-term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment.

          With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development.

          Conclusion

          As the aging of the Baby Boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all.

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          Most cited references86

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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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            Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture.

            The authors conducted a systematic review of published data on the association between diabetes mellitus and fracture. The authors searched MEDLINE through June 2006 and examined the reference lists of pertinent articles (limited to studies in humans). Summary relative risks and 95% confidence intervals were calculated with a random-effects model. The 16 eligible studies (two case-control studies and 14 cohort studies) included 836,941 participants and 139,531 incident cases of fracture. Type 2 diabetes was associated with an increased risk of hip fracture in both men (summary relative risk (RR) = 2.8, 95% confidence interval (CI): 1.2, 6.6) and women (summary RR = 2.1, 95% CI: 1.6, 2.7). Results were consistent between studies of men and women and between studies conducted in the United States and Europe. The association between type of diabetes and hip fracture incidence was stronger for type 1 diabetes (summary RR = 6.3, 95% CI: 2.6, 15.1) than for type 2 diabetes (summary RR = 1.7, 95% CI: 1.3, 2.2). Type 2 diabetes was weakly associated with fractures at other sites, and most effect estimates were not statistically significant. These findings strongly support an association between both type 1 and type 2 diabetes and increased risk of hip fracture in men and women.
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              Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.

              Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.
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                Author and article information

                Journal
                9100105
                2061
                Osteoporos Int
                Osteoporos Int
                Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
                0937-941X
                1433-2965
                15 February 2017
                07 February 2017
                May 2017
                01 November 2017
                : 28
                : 5
                : 1507-1529
                Affiliations
                [1 ]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
                [2 ]NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, UK
                [3 ]MRC ARUK Centre for Integrated Research in Musculoskeletal Ageing, Metabolic Bone Centre, Northern General Hospital, Sheffield, UK
                [4 ]Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK
                [5 ]Synthesis Medical NZ Ltd, Auckland, New Zealand
                [6 ]University of Notre Dame Australia, Sydney, Australia
                [7 ]Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
                [8 ]International Osteoporosis Foundation (IOF), Nyon, Switzerland
                [9 ]Department of Public Health, Epidemiology and Health Economics, University of Liège, Belgium
                [10 ]Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
                [11 ]NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
                [12 ]Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK
                [13 ]Institute for Health and Aging, Catholic University of Australia, Melbourne, Australia
                Author notes
                Corresponding author: Professor Eugene V. McCloskey, Address: MRC ARUK Centre for Integrated Research in Musculoskeletal Ageing, Metabolic Bone Centre, Northern General Hospital, Sheffield, UK, e.v.mccloskey@ 123456sheffield.ac.uk , Tel: +44 (0)114 271 4705, Fax: +44 (0)114 261 8775
                [*]

                Nicholas Harvey and Eugene McCloskey are joint first authors.

                Article
                PMC5392413 PMC5392413 5392413 ems71530
                10.1007/s00198-016-3894-y
                5392413
                28175979
                f2960fac-9a53-46c5-86f3-17904d28f369
                History
                Categories
                Article

                policy,prioritization,secondary prevention,primary prevention,Fragility fracture,osteoporosis,case-finding,disease awareness

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