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Review
. 2023 Jun 19:15:1759720X231177110.
doi: 10.1177/1759720X231177110. eCollection 2023.

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  1 , Antimo Moretti  2 , Annalisa Biffi  3 , Raffaella Ronco  3 , Gloria Porcu  3 , Giovanni Adami  4 , Rosaria Alvaro  5 , Riccardo Bogini  6 , Achille Patrizio Caputi  7 , Luisella Cianferotti  8 , Bruno Frediani  9 , Davide Gatti  4 , Stefano Gonnelli  10 , Andrea Lenzi  11 , Salvatore Leone  12 , Tiziana Nicoletti  13 , Marco Paoletta  2 , Annalisa Pennini  5 , Eleonora Piccirilli  14   15 , Raffaella Michieli  16 , Umberto Tarantino  14   15 , Maurizio Rossini  4 , Giovanni Corrao  3 , Maria Luisa Brandi  8 , Giovanni Iolascon  17
Affiliations
Review

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 et al. Ther Adv Musculoskelet Dis. .

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.

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Conflict of interest statement

GA declares personal fees from Theramex, Amgen, BMS, Lilly, Fresenius Kabi and Galapagos. LC declares personal fees from UCB Pharma, Abiogen Pharma, Bruno Farmaceutici, Sandoz, Metagenics. DG has received honoraria as consultant for Eli-Lilly, Organon, MSD Italia. SG has received honoraria as consultant for UCB Pharma. SM has received honoraria as consultant for UCB, Eli-Lilly, Amgen. MLB has received (i) honoraria from Amgen, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, UCB, (ii) grants and/or speaker: Abiogen, Alexion, Amgen, Bruno Farmaceutici, Echolight, Eli Lilly, Kyowa Kirin, SPA, Theramex, UCB Pharma, (iii) consultant: Alexion, Amolyt, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, UCB Pharma. GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA), and the Italian Ministry for University and Research (MIUR). He took part to a variety of projects that were funded by pharmaceutical companies (i.e., Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as member of Advisory Board from Roche. No other potential conflicts of interest relevant to this article were disclosed. MR declares personal fees from Amgen, ABBvie, BMS, Eli Lilly, Galapagos, Menarini, Novartis, Pfizer, Sandoz, Theramex and UCB outside the submitted work. RM took part to a project funded by Abiogen Pharma. GI received honoraria as speaker by Eli-Lilly, Menarini, UCB Pharma. The other authors declare that they have no conflict of interest.

Figures

Figure 1.
Figure 1.
Flowchart of study selection.
Figure 2.
Figure 2.
Risk of nonvertebral fracture between adherent (MPR ⩾ 80%) and nonadherent (MPR < 80%) subjects. Source: Adjustments. Lin 2011: site of osteoporotic fracture, gender, age. Soong 2013: comorbidity, concomitant drugs, gender, age. Sheehy 2009: demographic and clinical characteristics. MPR, medication possession ratio.
Figure 3.
Figure 3.
Health-related quality of life scores between adherent (>80% of pills consumed) and nonadherent (⩽80% of pills consumed) subjects. Source: McAlister 2019. OptQoL, Osteoporosis-Targeted Quality of Life questionnaire; SF-12, Short Form Health Survey, Disabilities of the Arm, Shoulder.
Figure 4.
Figure 4.
Risk of nonvertebral fractures between persistent (⩾12 months) and nonpersistent subjects (<12 months). Source: Adjustments. Chan 2016: demographic variables at baseline (age, gender and previous fractures) and in the 12 months prior to the index prescription to teriparatide for concomitant antiosteoporotic drugs and other drugs that can affect bone health, and comorbidities. Adams 2018: recruitment year, recruitment site, history of previous fractures, 10-year fracture probability (FRAX score), baseline fall risk (modified FRAT score), baseline comorbidity (Quan-Charlson score), previous or concomitant exposure to proton pump inhibitors, histamine H2 receptor antagonists, statins, estrogens and thiazolidinedione. Hsu 2020: age, gender, geographic region, hospital level and Charlson score.
Figure 5.
Figure 5.
Risk of fracture between subjects in continuous versus discontinuous antiosteoporotic treatment. Source: Cosman 2014: risk of refracture; Miller 1997, Black 2006: risk of vertebral fracture.
See this image and copyright information in PMC

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