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The Belgian Bone Club 2020 guidelines for the management of osteoporosis in postmenopausal women

  • D. Sanchez-Rodriguez
    Correspondence
    Corresponding author at: WHO Collaborating Center for Public Health aspects of musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU - Sart Tilman, Quartier Hôpital Avenue Hippocrate 13 (Bât. B23), 4000 Liège, Belgium. Tel.: +32 43 66 25 19.
    Affiliations
    WHO Collaborating Center for Public Health aspects of musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium

    Geriatrics Department, Rehabilitation Research Group, Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
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  • P. Bergmann
    Affiliations
    Department of Radioisotopes, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
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  • J.J. Body
    Affiliations
    Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
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  • E. Cavalier
    Affiliations
    Department of Clinical Chemistry, UnilabLg, University of Liège, CHU de Liège, Liège, Belgium
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  • E. Gielen
    Affiliations
    Gerontology and Geriatrics Section, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, University Hospitals, Leuven, Belgium
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  • S. Goemaere
    Affiliations
    Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium
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  • B. Lapauw
    Affiliations
    Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium
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  • MR Laurent
    Affiliations
    Geriatrics Department, Imelda Hospital, Bonheiden, Belgium
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  • S. Rozenberg
    Affiliations
    Department of Gynaecology-Obstetrics, Université Libre de Bruxelles, Brussels, Belgium
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  • G. Honvo
    Affiliations
    WHO Collaborating Center for Public Health aspects of musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
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  • C. Beaudart
    Affiliations
    WHO Collaborating Center for Public Health aspects of musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
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  • O. Bruyère
    Affiliations
    WHO Collaborating Center for Public Health aspects of musculo-skeletal health and ageing, Division of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
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      Highlights

      • A systematic methodology has been followed to construct the Belgian Bone Club 2020 guidelines.
      • The guideline has been produced taking all management of osteoporosis into account, from screening to monitoring.
      • The BBC 2020 guidelines provide updated algorithms for evidence and consensus-based clinical management of osteoporosis in postmenopausal women.

      Abstract

      Purpose

      To provide updated evidence-based guidelines for the management of osteoporosis in postmenopausal women in Belgium.

      Methods

      The Belgian Bone Club (BBC) gathered a guideline developer group. Nine “Population, Intervention, Comparator, Outcome” (PICO) questions covering screening, diagnosis, non-pharmacological and pharmacological treatments, and monitoring were formulated. A systematic search of MEDLINE, the Cochrane Database of Systematic Reviews, and Scopus was performed to find network meta-analyses, meta-analyses, systematic reviews, guidelines, and recommendations from scientific societies published in the last 10 years. Manual searches were also performed. Summaries of evidence were provided, and recommendations were further validated by the BBC board members and other national scientific societies’ experts.

      Results

      Of the 3840 references in the search, 333 full texts were assessed for eligibility, and 129 met the inclusion criteria. Osteoporosis screening using clinical risk factors should be considered. Patients with a recent (<2 years) major osteoporotic fracture were considered at very high and imminent risk of future fracture. The combination of bone mineral density measured by dual-energy X-ray absorptiometry and 10-year fracture risk was used to categorize patients as low or high risk. Patient education, the combination of weight-bearing and resistance training, and optimal calcium intake and vitamin D status were recommended. Antiresorptive and anabolic osteoporosis treatment should be considered for patients at high and very high fracture risk, respectively. Follow-up should focus on compliance, and patient-tailored monitoring should be considered.

      Conclusion

      BBC guidelines and 25 guideline recommendations bridge the gap between research and clinical practice for the screening, diagnosis, and management of osteoporosis.

      Keywords

      1. Background

      Osteoporotic fractures are a major cause of functional impairment, disability, pain, and mortality. However, the incidence and intensity of these adverse outcomes might be reduced if targeted state-of-the-art management of osteoporosis is applied. Comprehensive guidelines in osteoporosis should include recommendations about screening, diagnosis, treatment, and monitoring to allow their implementation in clinical practice [
      • Kanis J.A.
      • Cooper C.
      • Rizzoli R.
      • Reginster J.-Y.Y.
      Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF), European guidance for the diagnosis and management of osteoporosis in postmenopausal women.
      ]. Moreover, there is a need for country-specific guidelines because of differences in the epidemiology of the disease, health-care costs, and healthcare systems among countries.
      The Belgian Bone Club (BBC) is a multidisciplinary group of professionals that aims to address current unmet needs and improve quality of care for patients with osteoporosis and other metabolic bone diseases in Belgium (http://www.bbcbonehealth.org/). Herein, we provide an updated version of the previous BBC guidelines published in 2010 [
      • Body J.-J.
      • Bergmann P.
      • Boonen S.
      • Boutsen Y.
      • Devogelaer J.-P.
      • Goemaere S.
      • Kaufman J.-M.
      • Rozenberg S.
      • Reginster J.-Y.
      Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.
      ]. This update is necessary because new evidence has become available.

      2. Objective

      Our objective was to develop updated evidence-based guidelines for the screening, diagnosis, and management of osteoporosis in postmenopausal women in Belgium.

      3. Methods

      The BBC gathered a multidisciplinary group of specialists in clinical chemistry, endocrinology, epidemiology, gerontology and geriatrics, gynecology, internal medicine, nephrology, radiology, rheumatology, physiotherapy, primary care, and public health focused on updating the current existing guidelines for the management of postmenopausal osteoporosis [
      • Body J.-J.
      • Bergmann P.
      • Boonen S.
      • Boutsen Y.
      • Devogelaer J.-P.
      • Goemaere S.
      • Kaufman J.-M.
      • Rozenberg S.
      • Reginster J.-Y.
      Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.
      ]. The target end-users are primary care physicians as well as specialists involved in osteoporosis care in Belgium.

      3.1 Population, Intervention, Comparator, Outcome (PICO) questions

      Nine PICO questions covering screening, diagnosis, non-pharmacological and pharmacological treatments, monitoring, etc. were formulated and discussed among the BBC board members for approval (Table 1S).
      The BBC Guidelines Developer Group was composed of:
      • -
        A Working Group (CB, DSR, GH, OB) to propose a methodology, draft the 9 PICO questions, review the literature, and draft the synthesis of the literature.
      • -
        An Expert Panel (the Working Group and the BBC board members) to supervise the scope, draft the PICO questions, modify and approve the synthesis of the literature, propose recommendations and supervise the implementation of the project.
      • -
        A Voting Panel (8 BBC board members, and 28 Belgian expert clinicians selected by the BBC board to vote on the final recommendations.
      The Working Group decided to focus the literature search on network meta-analyses (NMA), meta-analyses (MA), systematic review (SR), guidelines and recommendations from scientific societies. This choice was made because NMA, MA, and SR are considered the highest level of categories of evidence [
      Explanation of the 2011 oxford centre for evidence-based medicine (OCEBM) levels of evidence (Background document).
      ]. A preliminary search confirmed that at least one MA or SR was available for each PICO question. This preliminary search found a substantial number of guidelines and recommendations: The Working Group decided to focus the search on guidelines from international scientific societies, the United States, and European countries, whose sociodemographic characteristics and perspective were considered most likely to be similar to those of Belgium.

      3.2 Systematic literature search

      The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed [
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gøtzsche P.C.
      • Ioannidis J.P.A.
      • Clarke M.
      • Devereaux P.J.
      • Kleijnen J.
      • Moher D.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
      ]. The 9 PICO questions (Table 1S) were used to conduct the literature search in MEDLINE (via Ovid), the Cochrane Database of Systematic Reviews (Ovid CDSR), and Scopus to find articles published in the last 10 years, since the publication of the current existing guidelines for the management of osteoporosis in Belgium [
      • Body J.-J.
      • Bergmann P.
      • Boonen S.
      • Boutsen Y.
      • Devogelaer J.-P.
      • Goemaere S.
      • Kaufman J.-M.
      • Rozenberg S.
      • Reginster J.-Y.
      Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.
      ]. NMA, MA, SR, and recommendations from scientific societies were identified. The search strategy was built, including the terms “Osteoporosis” AND (SR/MA OR “guideline”), and was limited to the period from 01/01/2010 to 22/06/2019 (Table 2S). The language was limited to English for pragmatic reasons. A manual search in the reference section of the selected papers and in the websites of the World Health Organization (WHO), the International Classification of Diseases (ICD), the International Osteoporosis Foundation (IOF), the European Medicines Agency (EMA), the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (ESCEO), and the BBC was performed to find additional information and more recent original studies if they were considered relevant. The Expert Panel was free to propose additional references, regardless of the study design, to answer the research questions.

      3.3 Eligibility criteria

      3.3.1 Inclusion criteria

      • -
        SR and/or MA about screening, monitoring or diagnostic tools in postmenopausal women diagnosed/at risk of osteoporosis (PICO 1–4 and 7–9).
      • -
        NMA and MA about the efficacy of pharmacological treatments, calcium, and vitamin D that include placebo-controlled studies and that have fracture as an outcome. Pharmacological interventions were selected on the basis of the National Institute of Health and Care Excellence recommendations regarding the drugs available for treating osteoporosis in Belgium (alendronate, bazedoxifene, denosumab, ibandronate, menopausal hormone therapy, raloxifene, risedronate, teriparatide, and zoledronate), combination therapy, and the investigational treatments abaloparatide and romosozumab (PICO 5–6).
      • -
        MA about the safety of pharmacological treatments, calcium, and vitamin D (all study designs and all outcomes were allowed for safety) (PICO 5–6).
      • -
        MA about physical activity in osteoporosis that have fracture, effects on BMD, physical function, activities of daily living (ADL), and falls as outcomes (PICO 5).
      • -
        Guidelines and recommendations from international scientific societies, the United States, and European countries (PICO 1–9).

      3.3.2 Exclusion criteria

      Studies on the following topics were excluded: acute fracture care, high-energy fractures, fracture healing, surgery and dental procedures, secondary osteoporosis, male sex, glucocorticoid-induced, cancer therapy-induced or premenopausal osteoporosis, and studies in languages other than English.
      All references were first screened on title/abstract by two independent reviewers (DSR and OB) who decided to include or exclude references based on the eligibility criteria. Interrater agreement was calculated to verify that the eligibility criteria were applied correctly and to increase the quality of the search. The two independent reviewers screened and discussed together the first 100 references. Agreement between the two reviewers was determined with kappa (k) statistics, where 0.81–1 was considered almost perfect agreement [
      • Landis J.R.
      • Koch G.G.
      An application of hierarchical kappa-type statistics in the assessment of majority agreement among multiple observers.
      ]. The results showed almost perfect agreement (k = 0.826, asymptotic standard error 0.098, p = 0.000). A consensus was reached for the 3 articles about which the 2 reviewers disagreed. The rest of the references were screened by the two reviewers independently.
      Selection of the full texts of the articles retrieved from the screening was also performed by the two independent reviewers. Any discrepancies of opinion between the two reviewers were solved by discussion and consensus and by the intervention of a third reviewer (CB) if necessary. Reasons for the exclusion of full-text papers were collected.

      3.4 Summaries of evidence

      According to the Oxford Centre for Evidence-Based Medicine Standards [
      Explanation of the 2011 oxford centre for evidence-based medicine (OCEBM) levels of evidence (Background document).
      ], we prioritized data from NMA, then MA, then SR, and then the guidelines. For pharmacological treatments, we were interested in evidence of their efficacy but also in their safety, with effect sizes where available. For screening and diagnosis tools, we were interested in metrological properties, benefits, and harms, if available. The different types of physical activity were categorized according to the Prevention of Falls Network Europe project (ProFANE) taxonomies for physical activity interventions [
      • Lamb S.E.
      • Jørstad-Stein E.C.
      • Hauer K.
      • Becker C.
      Development of a common outcome data set for fall injury prevention trials: the Prevention of Falls Network Europe consensus.
      ]. For guidelines, if more than one edition was available (same society and topic), the most updated version was selected. The best evidence retrieved from the literature review was written as a summary of evidence for each PICO question, and a first draft was sent to the Expert Panel. Comments from the panel about the summaries and additional studies provided by the panel were taken into account and compiled into a final version.

      3.5 Recommendations

      The Working Group prepared a draft for the recommendations that was modified by the Expert Panel through repeated comment rounds. The proposed recommendations were proposed to the Voting Panel by e-mail, asking the Voting Panel to vote on the recommendations considering benefits/risks, balance, cost (if possible), and their values and preferences.
      Each recommendation was presented with the question: Do you agree with the recommendation?” and 4 possible answers: “Strong do, Weak do, Weak don’t, and Strong don’t”. There was also a possibility to abstain due to a conflict of interest or insufficient expertise to judge a recommendation. Consensus on each recommendation (in favour or against) was defined as at least 75 % of the Voting Panel being either “weak” or “strong” in favour of or against a recommendation. If this criterion was not met, a consensus was not reached, and no recommendation was made. The strength of a recommendation was determined as “strong” if at least 75 % of the Voting Panel members rated a recommendation as “strong”. After the voting process, a summary of all votes was obtained. The manuscript was drafted by the Working Group and shared with the Expert Panel for review through repeated comment rounds. All read and approved the final version of the manuscript before submission.

      3.6 Conflicts of interest (COI)

      A specific strategy to avoid COI among BBC board members, Expert, and Voting Panel members was applied. All COI were collected prospectively, and those members with any COI relevant to a specific question were asked not to vote on that topic.

      4. Results

      The search strategy identified 5196 references, which resulted in 3840 studies after deleting duplicates obtained from the three databases. Following screening based on titles and abstracts according to the eligibility criteria, 333 papers were selected. After screening the full texts, 129 articles matched the inclusion criteria: 11 NMA [
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      The effect of combined resistance exercise training and vitamin D 3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis.
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      Effects of ground and joint reaction force exercise on lumbar spine and femoral neck bone mineral density in postmenopausal women: a meta-analysis of randomized controlled trials.
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      ] were included from the manual search.
      Fig. 1
      Fig. 1Detailed flow diagram of the literature search.

      Q1. HOW should osteoporosis be screened in postmenopausal women?

      Two MA [
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      Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density.
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      • Middleton J.C.
      • Nicholson W.K.
      • Kahwati L.C.
      Screening to prevent osteoporotic fractures.
      ], 3 SR [
      • Rubin K.H.
      • Friis-Holmberg T.
      • Hermann A.P.
      • Abrahamsen B.
      • Brixen K.
      Risk assessment tools to identify women with increased risk of osteoporotic fracture: complexity or simplicity? A systematic review.
      ,
      • Crandall C.J.
      Risk assessment tools for osteoporosis screening in postmenopausal women: a systematic review.
      ,
      • Nayak S.
      • Edwards D.L.
      • Saleh A.A.
      • Greenspan S.L.
      Performance of risk assessment instruments for predicting osteoporotic fracture risk: a systematic review.
      ], 7 guidelines [
      • Kanis J.A.
      • Cooper C.
      • Rizzoli R.
      • Reginster J.-Y.Y.
      Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF), European guidance for the diagnosis and management of osteoporosis in postmenopausal women.
      ,
      • Curry S.J.
      • Krist A.H.
      • Owens D.K.
      • Barry M.J.
      • Caughey A.B.
      • Davidson K.W.
      • Doubeni C.A.
      • Epling J.W.
      • Kemper A.R.
      • Kubik M.
      • Landefeld C.S.
      • Mangione C.M.
      • Phipps M.G.
      • Pignone M.
      • Silverstein M.
      • Simon M.A.
      • Tseng C.-W.
      • Wong J.B.
      Screening for osteoporosis to prevent fractures.
      ,
      • Brincat M.
      • Calleja-Agius J.
      • Erel C.T.
      • Gambacciani M.
      • Lambrinoudaki I.
      • Moen M.H.
      • Schenck-Gustafsson K.
      • Tremollieres F.
      • Vujovic S.
      • Rees M.
      • Rozenberg S.
      EMAS position statement: bone densitometry screening for osteoporosis.
      ,
      • Eastell R.
      • Rosen C.J.
      • Black D.M.
      • Cheung A.M.
      • Murad M.H.
      • Shoback D.
      • Hassan Murad M.
      • Shoback D.
      Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline.
      ,
      • Briot K.
      • Roux C.
      • Thomas T.
      • Blain H.
      • Buchon D.
      • Chapurlat R.
      • Debiais F.
      • Feron J.M.
      • Gauvain J.B.
      • Guggenbuhl P.
      • Legrand E.
      • Lehr-Drylewicz A.M.
      • Lespessailles E.
      • Tremollieres F.
      • Weryha G.
      • Cortet B.
      2018 update of French recommendations on the management of postmenopausal osteoporosis.
      ,
      • Camacho P.M.
      • Petak S.M.
      • Binkley N.
      • Clarke B.L.
      • Harris S.T.
      • Hurley D.L.
      • Kleerekoper M.
      • Lewiecki E.M.
      • Miller P.D.
      • Narula H.S.
      • Pessah-Pollack R.
      • Tangpricha V.
      • Wimalawansa S.J.
      • Watts N.B.
      American association of clinical endocrinologists and American college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis - 2016.
      ,
      • Compston J.
      • Cooper A.
      • Cooper C.
      • Gittoes N.
      • Gregson C.
      • Harvey N.
      • Hope S.
      • Kanis J.A.
      • McCloskey E.V.
      • Poole K.E.S.S.
      • Reid D.M.
      • Selby P.
      • Thompson F.
      • Thurston A.
      • Vine N.
      UK clinical guideline for the prevention and treatment of osteoporosis.
      ], and 1 articles from the manual search [
      • Merlijn T.
      • Swart K.M.A.
      • van der Horst H.E.
      • Netelenbos J.C.
      • Elders P.J.M.
      Fracture prevention by screening for high fracture risk: a systematic review and meta-analysis.
      ] contained relevant information for this PICO question.
      The SR and MA showed that more than 15 screening questionnaires composed of a varying number of clinical risk factors have been published. The diagnostic accuracy (i.e., sensitivity and specificity) of the screening tools for osteoporosis varied depending on the target populations assessed. However, none of the tools performed consistently better than the others [
      • Viswanathan M.
      • Reddy S.
      • Berkman N.
      • Cullen K.
      • Middleton J.C.
      • Nicholson W.K.
      • Kahwati L.C.
      Screening to prevent osteoporotic fractures.
      ,
      • Crandall C.J.
      Risk assessment tools for osteoporosis screening in postmenopausal women: a systematic review.
      ], and the number of risk factors assessed did not substantially influence performance, as questionnaires with more or fewer risk factors performed the same [
      • Nayak S.
      • Edwards D.L.
      • Saleh A.A.
      • Greenspan S.L.
      Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density.
      ,
      • Rubin K.H.
      • Friis-Holmberg T.
      • Hermann A.P.
      • Abrahamsen B.
      • Brixen K.
      Risk assessment tools to identify women with increased risk of osteoporotic fracture: complexity or simplicity? A systematic review.
      ]. Moreover, most of the risk assessment tools presented methodological issues and potentially lacked external validity outside of the cohorts in which they were developed [
      • Nayak S.
      • Edwards D.L.
      • Saleh A.A.
      • Greenspan S.L.
      Performance of risk assessment instruments for predicting osteoporotic fracture risk: a systematic review.
      ]. Therefore, insufficient evidence was found to recommend a particular osteoporosis screening tool over others.
      Two challenges underlie this lack of conclusive results: 1/ the existing tools assess different clinical outcomes, i.e., risk of low bone mineral density or risk of fracture [
      • Rubin K.H.
      • Friis-Holmberg T.
      • Hermann A.P.
      • Abrahamsen B.
      • Brixen K.
      Risk assessment tools to identify women with increased risk of osteoporotic fracture: complexity or simplicity? A systematic review.
      ,
      • Curry S.J.
      • Krist A.H.
      • Owens D.K.
      • Barry M.J.
      • Caughey A.B.
      • Davidson K.W.
      • Doubeni C.A.
      • Epling J.W.
      • Kemper A.R.
      • Kubik M.
      • Landefeld C.S.
      • Mangione C.M.
      • Phipps M.G.
      • Pignone M.
      • Silverstein M.
      • Simon M.A.
      • Tseng C.-W.
      • Wong J.B.
      Screening for osteoporosis to prevent fractures.
      ]; and 2/ the existing assessment tools do not exhibit a clear difference between their screening and diagnostic capabilities. These two terms are used indistinctly, and the lack of unified terminology may produce contradictory recommendations. For example, dual-energy X-ray absorptiometry (DXA) is considered a screening or diagnostic tool depending on the guideline assessed [
      • Curry S.J.
      • Krist A.H.
      • Owens D.K.
      • Barry M.J.
      • Caughey A.B.
      • Davidson K.W.
      • Doubeni C.A.
      • Epling J.W.
      • Kemper A.R.
      • Kubik M.
      • Landefeld C.S.
      • Mangione C.M.
      • Phipps M.G.
      • Pignone M.
      • Silverstein M.
      • Simon M.A.
      • Tseng C.-W.
      • Wong J.B.
      Screening for osteoporosis to prevent fractures.
      ,
      • Brincat M.
      • Calleja-Agius J.
      • Erel C.T.
      • Gambacciani M.
      • Lambrinoudaki I.
      • Moen M.H.
      • Schenck-Gustafsson K.
      • Tremollieres F.
      • Vujovic S.
      • Rees M.
      • Rozenberg S.
      EMAS position statement: bone densitometry screening for osteoporosis.
      ,
      • Compston J.
      • Cooper A.
      • Cooper C.
      • Gittoes N.
      • Gregson C.
      • Harvey N.
      • Hope S.
      • Kanis J.A.
      • McCloskey E.V.
      • Poole K.E.S.S.
      • Reid D.M.
      • Selby P.
      • Thompson F.
      • Thurston A.
      • Vine N.
      UK clinical guideline for the prevention and treatment of osteoporosis.
      ]. However, the screening and diagnosis of osteoporosis are considered different categories by the International Classification of Diseases 10 (ICD-10) and the World Health Organization (WHO) strategy, which recommend a two-step process to identify the disease: first, identification of risk factors, as a sensitive strategy for screening in large populations, and second, a diagnostic procedure using high specificity measurements from billable, technical devices that is applied in the population selected by the screening. The recommendations in the European guidance are aligned with the WHO’s strategy: risk factors are enumerated without mentioning any screening tool. Those women screened positively based on the presence of one or more risk factors should undergo a formal fracture risk evaluation (see Q3 and Q4).
      The major risk factors considered by the European guidance [
      • Kanis J.A.
      • Cooper C.
      • Rizzoli R.
      • Reginster J.-Y.Y.
      Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF), European guidance for the diagnosis and management of osteoporosis in postmenopausal women.
      ] and in the 7 guidelines [
      • Kanis J.A.
      • Cooper C.
      • Rizzoli R.
      • Reginster J.-Y.Y.
      Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF), European guidance for the diagnosis and management of osteoporosis in postmenopausal women.
      ,
      • Curry S.J.
      • Krist A.H.
      • Owens D.K.
      • Barry M.J.
      • Caughey A.B.
      • Davidson K.W.
      • Doubeni C.A.
      • Epling J.W.
      • Kemper A.R.
      • Kubik M.
      • Landefeld C.S.
      • Mangione C.M.
      • Phipps M.G.
      • Pignone M.
      • Silverstein M.
      • Simon M.A.
      • Tseng C.-W.
      • Wong J.B.
      Screening for osteoporosis to prevent fractures.
      ,
      • Brincat M.
      • Calleja-Agius J.
      • Erel C.T.
      • Gambacciani M.
      • Lambrinoudaki I.
      • Moen M.H.
      • Schenck-Gustafsson K.
      • Tremollieres F.
      • Vujovic S.
      • Rees M.
      • Rozenberg S.
      EMAS position statement: bone densitometry screening for osteoporosis.