View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Research Online @ ECU Edith Cowan University Research Online ECU Publications Post 2013 4-2-2019 Abdominal aortic calcification, bone mineral density and fractures: a systematic review and meta-analysis protocol Alexander J. Rodríguez Kevin Leow Pawel Szulc David Scott Peter Ebeling See next page for additional authors Follow this and additional works at: https://ro.ecu.edu.au/ecuworkspost2013 Part of the Medicine and Health Sciences Commons 10.1136/bmjopen-2018-026232 Rodríguez, A. J., Leow, K., Szulc, P., Scott, D., Ebeling, P., Sim, M., ... Lewis, J. R. (2019). Abdominal aortic calcification, bone mineral density and fractures: a systematic review and meta-analysis protocol. BMJ Open, 9(4), Article e026232. Available here This Journal Article is posted at Research Online. https://ro.ecu.edu.au/ecuworkspost2013/6124 Authors Alexander J. Rodríguez, Kevin Leow, Pawel Szulc, David Scott, Peter Ebeling, Marc Sim, Germaine Wong, Wai H. Lim, John T. Schousboe, Douglas P. Kiel, Richard L. Prince, and Joshua R. Lewis This journal article is available at Research Online: https://ro.ecu.edu.au/ecuworkspost2013/6124 Open access Protocol Abdominal aortic calcification, bone BMJ Open: first published as 10.1136/bmjopen-2018-026232 on 2 April 2019. Downloaded from mineral density and fractures: a systematic review and meta- analysis protocol Alexander J Rodríguez,1 Kevin Leow,2 Pawel Szulc,3 David Scott,1 Peter Ebeling,1 Marc Sim, 4,5 Germaine Wong,2 Wai H Lim,6,7 John T Schousboe,8 Douglas P Kiel,9 Richard L Prince,7,10 Joshua R Lewis2,4,5 To cite: Rodríguez AJ, Leow K, ABSTRACT Strengths and limitations of this study Szulc P, et al. Abdominal aortic Introduction Abdominal aortic calcification (AAC) is calcification, bone mineral associated with low bone mass and increased fracture density and fractures: a ► This study will use meta-regression to identify risk. Two previous meta-analyses have investigated the systematic review and meta- sources of heterogeneity and identify subgroups or analysis protocol. BMJ Open association between AAC and fracture. However, these subpopulations where abdominal aortic calcification 2019;9:e026232. doi:10.1136/ meta-analyses only identified articles until December (AAC) is more or less predictive of poorer outcomes. bmjopen-2018-026232 2016, undertook limited searches and did not explore ► To our knowledge, there has been no systematic potential sources of between-study heterogeneity. We aim ► Prepublication history and review and meta-analysis that has investigated the additional material for this to undertake a sensitive and comprehensive assessment of association between AAC and bone mineral density paper are available online. To the relationship between AAC, bone mineral density (BMD) as (BMD), which is along the hypothesised causal path- view these files, please visit well as prevalent and incident fractures. way to fracture. the journal online (http:// dx. doi. Methods We will search MEDLINE, EMBASE, Web of ► The main limitation of this review is that causality org/ 10. 1136/ bmjopen- 2018- Science core collection and Google Scholar (top 200 articles cannot be established due to the observational na- 026232). sorted by relevance) from their inception to 1 June 2018. ture of the studies. A further limitation is the differences in imaging Received 23 August 2018 Reference lists of included studies and previous systematic ► Revised 19 December 2018 reviews will be hand searched for additional eligible studies. modality, measurement and reporting of AAC across Accepted 31 January 2019 Retrospective and prospective cohort studies (cross- studies but we attempted to overcome this by ex- sectional, case–control and longitudinal) reporting the ploring these aspects in prespecified subanalyses. http://bmjopen.bmj.com/ association between AAC, BMD and fracture at any site will be included. At least two investigators will independently: (A) evaluate study eligibility and extract data, with a third INTRODUCTIOn investigator to adjudicate when discrepancies occur, (B) assess study quality by the Newcastle-Ottawa Scale for Vascular and bone diseases are both chronic each cohort/study. The meta-analysis will be reported in age-related disease that share many common adherence to the Meta-analysis of Observational Studies in dietary and lifestyle risk factors and cause 1 Epidemiology criteria. AAC will be grouped as either: (1) AAC considerable morbidity and mortality. on 26 May 2019 by guest. Protected copyright. present or absent, (2) AAC categorised as ‘low’ (referent— Atherosclerotic lesions in the abdominal lowest reported group) versus ‘high’ (all other groups) or aorta generally begin around the major vessel (3) dose–response when AAC was assessed in ≥3 groups. bifurcations and branching arteries such as Where primary event data were reported in individual the inferior mesenteric artery and the lumbar studies, pooled risk differences and risk ratios with 95% CI arteries that supply blood and nutrients to the will be calculated, from which, a summary estimate will lumbar vertebrae.2 Occlusion of these vessels be determined using DerSimonian-Laird random effects may causes ischaemia in the lumbar spine and © Author(s) (or their models. For the AAC and BMD pooled analyses, estimates may result in disc degeneration and asymp- employer(s)) 2019. Re-use will be expressed as standardised mean difference with tomatic vertebral fractures.3 Additionally, permitted under CC BY-NC. No 95% CI. We will examine the likelihood of publication bias commercial re-use. See rights the underlying processes regulating arterial and permissions. Published by and where possible, investigate potential reasons for calcification share many similarities to bone BMJ. between-study heterogeneity using subgroup analyses and physiology4 and calcified atherosclerotic For numbered affiliations see meta-regression. plaques release both local and systemic osteo- The study will be submitted end of article. Ethics and dissemination chondrogenic factors that may affect regional to a peer- reviewed journal and disseminated via research and systemic bone homoeostasis.5 Conversely Correspondence to presentations. circulating levels of factors regulating bone Dr Joshua R Lewis; PROSPERO registration number CRD42018088019. joshua. lewis@ uwa. edu. au homoeostasis may also regulate vascular Rodríguez AJ, et al. BMJ Open 2019;9:e026232. doi:10.1136/bmjopen-2018-026232 1 Open access 6 calcifications with a number of studies demonstrating case–control and cross-sectional studies that report eli- BMJ Open: first published as 10.1136/bmjopen-2018-026232 on 2 April 2019. Downloaded from osteoporosis and bone mineral density (BMD) being a gible exposure(s) and outcome(s). risk factor for cardiovascular disease (CVD).7 8 b. AAC assessed by any methodology. Assessment of lateral spine images is often undertaken c. Report any BMD measure or prevalent or incident to detect prevalent vertebral fractures and has been shown fracture outcome. to improve fracture prediction.9–11 These images can also be used to assess the degree of abdominal aortic calci- Exclusion criteria fication (AAC). To date, there are conflicting findings a. Reviews of existing literature. as to whether AAC is associated with BMD and fractures and whether or not these associations are due to ageing, Exposure shared fracture risk factors or are a non-traditional AAC identified from either radiography, dual X-ray independent fracture risk factor. Recent meta-analyses absorptiometry (DXA) machine or CT. AAC will be 12 13 published in 2016 and 2017, looking at observational presented as: studies, showed that people with any or high AAC were at a. AAC present or absent. greater risk of fractures than those with no or low AAC. b. AAC categorised as low (referent—lowest reported 12 However, the previous studies by Chen and Yu and group) versus moderate to high (all other reported 13 Wei et al only identified a limited number of articles groups combined). due to the search strategies employed (searches found c. AAC dose–response when AAC was assessed in three or 91 and 105 articles, respectively) and the meta-anal- more groups categorised as low (lowest reported cate- yses missed many of the known studies in the area (by gory), moderate (middle reported category[ies]) and 14 way of example—both studies missed Wang et al. ). For high (highest reported category). example, our recent search identified 1561 potentially eligible reports. Furthermore, both meta-analyses iden- Outcomes tified unexplained moderate-high heterogeneity that 1. BMD (by site). needs to be explored further. As such uncertainty exists 2. Prevalent fractures (by fracture site). as to the importance of identifying AAC for incident frac- 3. Incident fractures (by fracture site). ture risk, particularly with respect to AAC cut-points, types of fracture and potential explanations for the observed Cohort characteristics for meta-regression (where available) between-study heterogeneity. We will, therefore, under- ► Cohort age (cohort mean). take a meta-analysis of studies reporting on AAC, BMD at ► Gender (% female). any site and prevalent and incident fractures at any site. ► Years since menopause (cohort mean). ► Hormone replacement therapy (%). ► Modality of assessing AAC (DXA, standard radiograph http://bmjopen.bmj.com/ OBJECTIVES or CT). 1. To determine the association between AAC with BMD ► Cut-points chosen for comparison (low vs high,