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

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; Giovanni Iolascon

doi:10.1177/1759720X231177110

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

Ther Adv Musculoskelet Dis. 2023 Jun 19:15:1759720X231177110. doi: 10.1177/1759720X231177110. eCollection 2023.

Authors

Silvia Migliaccio¹, Antimo Moretti², Annalisa Biffi³, Raffaella Ronco³, Gloria Porcu³, Giovanni Adami⁴, Rosaria Alvaro⁵, Riccardo Bogini⁶, Achille Patrizio Caputi⁷, Luisella Cianferotti⁸, Bruno Frediani⁹, Davide Gatti⁴, Stefano Gonnelli¹⁰, Andrea Lenzi¹¹, Salvatore Leone¹², Tiziana Nicoletti¹³, Marco Paoletta², Annalisa Pennini⁵, Eleonora Piccirilli^{14

15}, Raffaella Michieli¹⁶, Umberto Tarantino^{14

15}, Maurizio Rossini⁴, Giovanni Corrao³, Maria Luisa Brandi⁸, Giovanni Iolascon¹⁷

Affiliations

¹ Department of Movement, Human and Health Sciences, Foro Italico University, Rome, Italy.
² Department of Medical and Surgical Specialties and Dentistry, University of Campania "Luigi Vanvitelli," Napoli, Italy.
³ Unit of Biostatistics, Epidemiology, and Public Health, Department of Statistics and Quantitative Methods, National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy.
⁴ Rheumatology Unit, University of Verona, Verona, Italy.
⁵ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
⁶ Local Health Unit (USL) Umbria, Italy.
⁷ Department of Pharmacology, School of Medicine, University of Messina, Italy.
⁸ Italian Bone Disease Research Foundation (FIRMO), Florence, Italy.
⁹ Department of Medicine, Surgery and Neurosciences, Rheumatology Unit, Azienda Ospedaliero-Universitaria Senese, University of Siena, Siena, Italy.
¹⁰ Department of Medicine, Surgery and Neuroscience, Policlinico Le Scotte, University of Siena, Siena, Italy.
¹¹ Department of Experimental Medicine, Viale del Policlinico, Sapienza University of Rome, Rome, Italy.
¹² AMICI Onlus, Associazione nazionale per le Malattie Infiammatorie Croniche dell'Intestino, Milan, Italy.
¹³ CnAMC, Coordinamento nazionale delle Associazioni dei Malati Cronici e rari di Cittadinanzattiva, Rome, Italy.
¹⁴ Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata," Rome, Italy.
¹⁵ Department of Orthopedics and Traumatology, "Policlinico Tor Vergata" Foundation, Rome, Italy.
¹⁶ Italian Society of General Medicine and Primary Care (SIMG), Florence, Italy.
¹⁷ Department of Medical and Surgical Specialties and Dentistry, University of Campania "Luigi Vanvitelli," Via De Crecchio, 6, Napoli, Italy.

Abstract

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.

Keywords: adherence; bisphosphonates; compliance; discontinuation; fragility fractures; medication vacation; osteoporosis; persistence.

Publication types

Review