This systematic review will be reported according to the recommended items in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) checklist [14]. This protocol for this systematic review is registered with International Prospective Register for Systematic Reviews (PROSPERO) database (Registration Number: CRD42021245075).
Eligibility Criteria:
Studies will be included in the systematic review according to the following PICO criteria: participants (population), intervention, comparison, outcome(s) of interest, and study design.
Participants (Population):
Studies involving patients aged ≥ 50 years (regardless of sex), with any type of fragility or osteoporotic fracture will be included in the systematic review. The reason for the inclusion of a specific age group is that, by definition, an FLS targets this age group [15]. We will exclude studies involving patients with fractures associated with trauma or road traffic accidents. Studies involving other bone-associated diseases such as osteomyelitis, tumors, and gout will be excluded.
Intervention:
The systematic review will examine studies that evaluated the Fracture Liaison Service program/ secondary fracture prevention program implemented at any healthcare setting (hospitals and/or community). We will also include studies that implemented FLS/secondary fracture prevention programs as digital health or telemedicine intervention. In addition, FLS with geriatric assessment programs will also be included in the current systematic review. However, studies involving geriatric assessment programs alone and trauma care programs will be excluded from the review.
Comparison:
The comparison group is usual care (non-FLS care) for fragility fracture patients practiced in any healthcare setting.
Outcome(s) of Interest:
The primary outcome will be the proportion of fragility fracture patients evaluated for subsequent fracture risk. This is often indicated by the number of fracture patients that were assessed for future fracture risk divided by the total number of fracture patients recruited in the study. Measurement of proportion of fracture risk assessment in study arms (FLS vs. non-FLS care) is also reported using crude and adjusted prevalence ratios, odds ratios, and relative risk based on study design. Secondary outcomes will be types of fracture risk prediction tools used to predict subsequent fracture risk. Potential fracture risk assessment tools may include the following: FRAX tool, QFracture, DeFRA, or Garvan. Another secondary outcome will be rates of bone mineral density (BMD) testing (a radiological test to measure bone density and predict the risk of bone fracture) performed as a part of fracture risk assessment protocol within the FLS program.
Study design:
Eligible studies will be randomized controlled trials and non-randomized experimental study design (quasi-experimental, pre-post designs, time-series analysis) reporting on the outcomes of the FLS program. Observational studies with a control group (case-control, prospective, and retrospective cohort) will also be included to determine the proportion of fragility fracture patients assessed for subsequent fracture risk. We will exclude qualitative studies, scoping reviews, narrative reviews, editorials, protocols, case reports, case series, cross-sectional studies, conference abstract, opinion articles, systematic reviews, and meta-analyses. Studies published in languages other than English will also be excluded. The literature search will not be restricted to the context and year of publication.
Information sources and search strategy:
A systematic electronic literature search will be conducted to assess the effect of FLS in improving fracture risk assessment among fragility fracture patients. We will search four major electronic databases including PubMed, Cochrane Library, EBSCO CINAHL Plus, and Embase. Non-published gray literature (conference papers, student thesis, and public repositories) will also be explored to extract relevant literature. We will also appraise the reference list of included studies to identify potentially relevant articles. A detailed search strategy will be used to explore these databases. The search strategy will be designed and carried out by both the reviewers with the help of an information scientist at Gerstein Library. The key search terms will be clustered into four categories of interest: Population (Patients aged ≥ 50 years with fragility fractures), intervention (Fracture Liaison Service or secondary fracture prevention Program), comparison (non-FLS or standard care), and outcome (a measurement of the proportion of fracture risk assessment performed and BMD testing). Additionally, we will use indexed keywords in Medical Subject Headings (MeSH) to ensure uniformity of search terms (Appendix 1). Appendix 2 illustrates the preliminary search strategy carried out on Embase.
Selection of studies:
All the articles extracted from the electronic databases will be uploaded into Endnote [14]. The references from Endnote will then be imported into Covidence software to streamline the process of the systematic review. The articles will be screened by two reviewers (A.A and J.S) independently. In the first step, the articles will be screened by study titles using the Covidence software. Then, the abstract of shortlisted studies will be screened. In the second step, full texts of selected articles will be retrieved and examined against the eligibility criteria. At last, the references of selected studies will be hand-searched to extract any potentially relevant studies missed in the initial searched strategy. A pre-structured screening form will be designed, and pilot tested to ensure the uniformity and reliability of screened studies among two reviewers. Both reviewers will define the intervention and outcomes of interest after screening the articles to verify the relevance of the studies. Each reviewer will provide a strong justification for excluding full-text articles. The disagreement between the two reviewers will be resolved by negotiation and discussion in a consensus meeting. The selection process of studies will be reported using a PRISMA flow diagram (Appendix 3).
Data Collection process:
Data extraction will be performed onto a customized excel sheet by two reviewers (A.A and J.S) independently. The data extraction tables completed by both the reviewers will be matched to confirm that the main findings are documented. A third reviewer in the data extraction process will be involved if any discordant information is witnessed. The preliminary table for data extraction is illustrated in Appendix 4. The table includes the title of the study, primary author, date of publication, date of extraction, country of study, reviewer name, the objective of the study, study population, type of fracture prevention program, study outcomes (proportions, prevalence ratios, odds ratios, and relative risks for improvement in fracture risk assessment and BMD testing), eligibility criteria, reasons for exclusion, and quality appraisal of selected studies. The data extraction tables will also provide a summary of all the included studies. A preliminary data extraction table is presented in Appendix 3.
Quality Assessment:
The quality of the selected studies will be assessed by standardized quality assessment tools which will be performed by the two reviewers (A.A and J.S) independently. The JBI critical appraisal tools will be used to assess methodological quality of all the included studies [16]. We selected JBI because the tool has a separate checklist for different study designs and assesses multiple aspects of methodological quality such as eligibility criteria, study subjects and setting, the validity of outcome measurement, confounding factors and strategies to account for confounding, and appropriateness of statistical analysis. Each component of the checklist is judged as either the information is present in sufficient detail or not and classified as “yes”, “no”, “Unclear”, and “not applicable”. The reviewer will assign a score of 1 for “yes”. The sum of scores for each “yes” in the checklist will be used to judge the risk of bias. We will not exclude any study with a high risk of bias (low “yes” counts); instead, we will report methodological quality for each included study in the review.
Synthesis of included studies:
In the first step, a brief quantitative summary of demographic variables such as year of publication, study setting, study design, sample size, types of FLS program, and fracture risk assessment tools will also be performed. These findings will be presented in the descriptive table of the result section. Later, the rates of BMD testing will be reported. The meta-analysis will be carried out if ≥ 2 studies can be pooled, with consideration of statistical and clinical heterogeneity. All the meta-analyses will be performed in Review Manager Software [17]. The studies included in the systematic review will be reviewed for inclusion in the meta-analysis. Studies with no denominator data or control group or pre-post experimental design will be excluded from the meta-analysis. Since heterogeneity in the data is expected a priori, we will use the random effects model to estimate the pooled effects. Forest plots will be utilized to demonstrate the extent of heterogeneity among selected studies. Statistical heterogeneity will be quantified by estimating I2 statistic. Also, potential sources of heterogeneity will be investigated further by subgroup analyses according to type of FLS model and baseline characteristics. In the second step, the findings from the articles will be synthesized descriptively to report on common results among the selected articles including types of secondary fracture prevention programs, qualitative and quantitative tools used for fracture risk assessment, and types of healthcare settings implementing FLS.