We have registered this study on INPLASY202040153. It is developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol statement guidelines .
Eligibility criteria for study selection
This study will only include randomized controlled trials (RCTs) of alendronate for the treatment of patients with AS. Besides RCTs, we will exclude any other studies, such as non-clinical trials, non-RCTs, and quasi-RCTs.
The experimental intervention are any forms of alendronate.
The control intervention could be any treatments, such as placebo, other medications, and alternative therapies. However, we will exclude studies using any types of alendronate, including its combination with other managements as their comparators.
Any adult participants (more than 18 years old) with a definite diagnosis of AS will be included in spite of their race, gender, educational background, and duration of AS.
Bone densitometry (as reported in the trials by any instruments or tools).
Pain intensity (as reported in the trial by any pain scales);
Quality of life (as reported in the trial by any tools, such as Ankylosing Spondylitis Quality of Life questionnaire);
Disease activity (as reported in the trial by any indexes, such as Bath Ankylosing Spondylitis Disease Activity Index);
Functional status (as reported in the trial by any scores, such as Bath Ankylosing Spondylitis Functional Index); and
Electronic databases search
Two authors will carry out a comprehensive literature search from the below electronic databases: PUBMED, EMBASE, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure. All these electronic databases will be searched from their commencement to the January 31, 2020 without language and publication status limitations. Any potential randomized controlled trials (RCTs) that explored the efficacy and safety of alendronate for the treatment of patients with AS will be included. An example of detailed search strategy for PUBMED is presented (table 1). We will modify similar search strategies for other electronic databases.
Other literature sources search
We will search other literature resources, such as Google Scholar, websites of clinical trial registry, dissertations, and reference lists of included trials.
Records from all literature source searches will be imported into EndNote X9 to remove all duplicated studies. Two authors will firstly identify records by scanning titles and abstracts, and unrelated studies will be eliminated. Then, full-text of remaining studies will be read cautiously based on the predefined eligibility criteria. Any divergences will be figured out with the help of a third author. The process of study selection will be exerted in a flow diagram (Figure 1).
Data collection and management
Two authors will independently extract data from each included trial in accordance with the predefined data collection form. Any uncertainties will be resolved by another author and a consensus will be reached finally. The collected information is as follows:
Study details: title, first author, publication date, location, et al.
Study methods: randomization specifics, blinding, allocation, follow-up information, et al.
Patient characteristics: age, sex, sample size, duration and severity of AS, et al.
Intervention and control details: treatment duration, dosage, frequency, et al.
Outcomes: outcome measurements reported in the trial, adverse events, et al.
Others: funding information, conflict of interest, et al.
Dealing with unclear or missing data
Any unclear or insufficient data will be obtained from original authors with email or phone. If it is not achievable, we will perform data analysis based on the available data, and will discuss its impacts on study findings.
Risk of bias assessment
Study quality of each included trial will be evaluated by two independent authors using Cochrane risk of bias tool, which examines 7 domains. We will rate each source of bias as low, unclear or high. Any different views will be worked out with the help of another author through discussion.
Treatment effect measurement
In this study, we will use mean difference or standardized mean difference and 95% confidence intervals (CIs) to evaluate the treatment effect for continuous data, and risk ratio and 95% CIs to appraise the treatment effect for dichotomous data.
RevMan 5.3 software will be employed for all data analysis and meta-analysis if it is possible. I² test will be used for heterogeneity identification. I² ≤50% suggests reasonable heterogeneity, and a fixed-effect model will be exerted. Otherwise, I² >50% means substantial heterogeneity, and a random-effect model will be employed. If ample data is extracted from sufficient trials with low heterogeneity, we will carry out meta-analysis to explain the results. On the other hand, we will perform subgroup analysis and sensitivity analysis to test possible sources of significant heterogeneity. If meta-analysis is deemed not to be conducted, we will elaborate study results using a narrative description.
Subgroup analysis will be developed to investigate the possible sources of significant heterogeneity according to the characteristics of study, types of intervention and controls, and different outcome measurements.
A sensitivity analysis will be carried out to test the robustness and stability of pooled results by taking away low quality trials or trials reporting data missing.
If it is possible to include at least 10 trials on one outcome, we will examine the possible reporting bias using funnel plot and Egger’s regression test [25-26].
This study will be disseminated at a peer-reviewed journal or will be presented a scientific conference.