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Background: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk.Objective: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines.Design: Systematic review and meta-analysis.Data sources and methods: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in 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 fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change.Results: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site.Conclusion: The Task Force formulated recommendations on sequential therapy, which is the fi

Purpose: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. Results: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9–16] and 6 (95% CI 5–8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. Conclusion: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures.

Summary : Randomized clinical trials and observational studies on the implementation of clinical governance models, in patients who had experienced a fragility fracture, were examined. Literature was systematically reviewed and summarized by a panel of experts who formulated recommendations for the Italian guideline. Purpose: After experiencing a fracture, several strategies may be adopted to reduce the risk of recurrent fragility fractures and associated morbidity and mortality. Clinical governance models, such as the fracture liaison service (FLS), have been introduced for the identification, treatment, and monitoring of patients with secondary fragility fractures. A systematic review was conducted to evaluate the association between multidisciplinary care systems and several outcomes in patients with a fragility fracture in the context of the development of the Italian Guidelines. Methods: PubMed, Embase, and the Cochrane Library were investigated up to December 2020 to update the search of the Scottish Intercollegiate Guidelines Network. Randomized clinical trials (RCTs) and observational studies that analyzed clinical governance models in patients who had experienced a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in 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 bone mineral density values, antiosteoporotic therapy initiation, adherence to antiosteoporotic medications, subsequent fracture, and mortality risk, while secondary outcomes were quality of life and physical performance. Results: Fifteen RCTs and 62 observational studies, ranging from very low to low quality for bone mineral density values, antiosteoporotic initiation, adherence to antiosteoporotic medications, subsequent fracture, mortality, met

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 t

Purpose: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. Methods: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. Conclusion: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

Background: Fragility 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. Purpose: This 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. Methods: The 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. Results: Overall, 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. Conclusions: The 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 r

Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints). Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization. Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45–4.77; 2.16, 1.43–3.26; 2.83, 1.74–4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93–3.49; 1.84, 1.26–2.69; 4.15, 1.76–9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32–2.13; 1.83, 1.43–2.33; 1.49, 1.16–1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63–3.85; 2.38, 1.56–3.63; 1.82, 1.43–2.33). Considering specific subgroups (i.e., Caucasian patients, high quality stu