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Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a ‘medication holiday,’ should be planned by healthcare professionals. Objectives: We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Design: Systematic review. Data Sources and Methods: We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events. Results: Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20–0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25–0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous versus discontinuous treatment. Conclusion: Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur.

Supplemental material, sj-docx-2-tab-10.1177_1759720X231177110 for Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on ‘Diagnosis, risk stratification, and continuity of care of fragility fractures’ based on a systematic literature review by Silvia Migliaccio, Antimo Moretti, Annalisa Biffi, Raffaella Ronco, Gloria Porcu, Giovanni Adami, Rosaria Alvaro, Riccardo Bogini, Achille Patrizio Caputi, Luisella Cianferotti, Bruno Frediani, Davide Gatti, Stefano Gonnelli, Andrea Lenzi, Salvatore Leone, Tiziana Nicoletti, Marco Paoletta, Annalisa Pennini, Eleonora Piccirilli, Raffaella Michieli, Umberto Tarantino, Maurizio Rossini, Giovanni Corrao, Maria Luisa Brandi and Giovanni Iolascon in Therapeutic Advances in Musculoskeletal Disease

Supplemental material, sj-docx-3-tab-10.1177_1759720X231177110 for Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on ‘Diagnosis, risk stratification, and continuity of care of fragility fractures’ based on a systematic literature review by Silvia Migliaccio, Antimo Moretti, Annalisa Biffi, Raffaella Ronco, Gloria Porcu, Giovanni Adami, Rosaria Alvaro, Riccardo Bogini, Achille Patrizio Caputi, Luisella Cianferotti, Bruno Frediani, Davide Gatti, Stefano Gonnelli, Andrea Lenzi, Salvatore Leone, Tiziana Nicoletti, Marco Paoletta, Annalisa Pennini, Eleonora Piccirilli, Raffaella Michieli, Umberto Tarantino, Maurizio Rossini, Giovanni Corrao, Maria Luisa Brandi and Giovanni Iolascon in Therapeutic Advances in Musculoskeletal Disease

BackgroundFragility fractures are a major public health concern owing to their worrying and growing burden and their onerous burden upon health systems. There is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at a greater risk for further fractures, thus suggesting the potential for secondary prevention in this field.PurposeThis guideline aims to provide evidence-based recommendations for recognizing, stratifying the risk, treating, and managing patients with fragility fracture. This is a summary version of the full Italian guideline.MethodsThe Italian Fragility Fracture Team appointed by the Italian National Health Institute was employed from January 2020 to February 2021 to (i) identify previously published systematic reviews and guidelines on the field, (ii) formulate relevant clinical questions, (iii) systematically review literature and summarize evidence, (iv) draft the Evidence to Decision Framework, and (v) formulate recommendations.ResultsOverall, 351 original papers were included in our systematic review to answer six clinical questions. Recommendations were categorized into issues concerning (i) frailty recognition as the cause of bone fracture, (ii) (re)fracture risk assessment, for prioritizing interventions, and (iii) treatment and management of patients experiencing fragility fractures. Six recommendations were overall developed, of which one, four, and one were of high, moderate, and low quality, respectively.ConclusionsThe current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture to benefit from secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost.

Supplemental material, sj-docx-4-tab-10.1177_1759720X231177110 for Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on ‘Diagnosis, risk stratification, and continuity of care of fragility fractures’ based on a systematic literature review by Silvia Migliaccio, Antimo Moretti, Annalisa Biffi, Raffaella Ronco, Gloria Porcu, Giovanni Adami, Rosaria Alvaro, Riccardo Bogini, Achille Patrizio Caputi, Luisella Cianferotti, Bruno Frediani, Davide Gatti, Stefano Gonnelli, Andrea Lenzi, Salvatore Leone, Tiziana Nicoletti, Marco Paoletta, Annalisa Pennini, Eleonora Piccirilli, Raffaella Michieli, Umberto Tarantino, Maurizio Rossini, Giovanni Corrao, Maria Luisa Brandi and Giovanni Iolascon in Therapeutic Advances in Musculoskeletal Disease

Supplemental material, sj-docx-5-tab-10.1177_1759720X231177110 for Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on ‘Diagnosis, risk stratification, and continuity of care of fragility fractures’ based on a systematic literature review by Silvia Migliaccio, Antimo Moretti, Annalisa Biffi, Raffaella Ronco, Gloria Porcu, Giovanni Adami, Rosaria Alvaro, Riccardo Bogini, Achille Patrizio Caputi, Luisella Cianferotti, Bruno Frediani, Davide Gatti, Stefano Gonnelli, Andrea Lenzi, Salvatore Leone, Tiziana Nicoletti, Marco Paoletta, Annalisa Pennini, Eleonora Piccirilli, Raffaella Michieli, Umberto Tarantino, Maurizio Rossini, Giovanni Corrao, Maria Luisa Brandi and Giovanni Iolascon in Therapeutic Advances in Musculoskeletal Disease

Supplemental material, sj-docx-1-tab-10.1177_1759720X231177110 for Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on ‘Diagnosis, risk stratification, and continuity of care of fragility fractures’ based on a systematic literature review by Silvia Migliaccio, Antimo Moretti, Annalisa Biffi, Raffaella Ronco, Gloria Porcu, Giovanni Adami, Rosaria Alvaro, Riccardo Bogini, Achille Patrizio Caputi, Luisella Cianferotti, Bruno Frediani, Davide Gatti, Stefano Gonnelli, Andrea Lenzi, Salvatore Leone, Tiziana Nicoletti, Marco Paoletta, Annalisa Pennini, Eleonora Piccirilli, Raffaella Michieli, Umberto Tarantino, Maurizio Rossini, Giovanni Corrao, Maria Luisa Brandi and Giovanni Iolascon in Therapeutic Advances in Musculoskeletal Disease