Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2020; 26(35): 5362-5374
Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5362
Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease
Sofia Kärnsund, Bobby Lo, Flemming Bendtsen, Jakob Holm, Johan Burisch
Sofia Kärnsund, Bobby Lo, Flemming Bendtsen, Johan Burisch, Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre 2650, Denmark
Jakob Holm, Department of Endocrinology, Copenhagen University Hospital Herlev, Herlev 4600, Denmark
Author contributions: All authors have made significant contributions to the research in this study; all authors approved the submitted version of the manuscript and the authorship list; Kärnsund S and Lo B contributed to acquisition, interpretation and analysis of data; Kärnsund S contributed to writing of manuscript; Lo B contributed to critical revision for important intellectual content; Bendtsen F and Burisch J contributed to conception and design of study, critical revision for important intellectual content; Burisch J contributed to finally approval of submitted manuscript.
Conflict-of-interest statement: Burisch J received consulting fees from Celgene, Janssen-Cilag, AbbVie, Tillots Pharma and Ferring; lecture fees from Abbvie, Pfizer, MSD, Pharmacosmos and Takeda Pharma; unrestricted grant support from Takeda Pharma, MSD, AbbVie and Tillots Pharma. Holm J has participated as a sub investigator in studies by Amgen and MSD and received payment for lectures sponsored by Amgen and LEO Pharma. Kärnsund S, Lo B and Bendtsen F have nothing to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Sofia Kärnsund, BSc, Doctor, Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre, Kettegård Alle 30, Hvidovre 2650, Denmark.
Received: March 28, 2020
Peer-review started: March 28, 2020
First decision: April 25, 2020
Revised: May 4, 2020
Accepted: August 22, 2020
Article in press: August 22, 2020
Published online: September 21, 2020
Research background

The inflammatory bowel diseases (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated disorders of the digestive tract. Being diagnosed with IBD is considered a risk factor for the development of osteoporosis. The consequence of development of osteoporosis is the increased risk of pathological fractures that in turn are associated with great economic and psychological burden. Several studies have investigated the relationship between inflammatory bowel diseases and osteoporosis but differences in study design and study populations, as well as inconsistent results and diverging interpretations of them, make it difficult to draw firm conclusions.

Research motivation

Considering the severe consequences of osteoporosis, research on risk factors and prevalence of the disease in IBD patients is of great importance in order to conclude how prevailing the disease is in this patient group and its subgroups. It may give clues on how guidelines for screening and treatment of osteoporosis in IBD-patients should be developed, as well pinpointing what areas need more research.

Research objectives

The objectives with this research was to assess the prevalence of osteoporosis among IBD patients compared to healthy individuals, as well as the disease course of osteoporosis or low BMD in IBD patients. We also aimed to assess risk factors associated with osteoporosis and low BMD in IBD patients with the intention to find more substantial evidence as to the cause of osteoporosis or low BMD in this patient group.

Research methods

For this systematic review, we searched databases including EMBASE and PubMed as well as abstracts from 2014-2018 presented at the United European Gastroenterology Week, the European Crohn’s and Colitis Organisation congress, and Digestive Disease Week were screened. Studies were eligible for inclusion if they investigated either the prevalence of osteoporosis or osteopenia and/or risk factors for osteoporosis or low bone mineral density (BMD in IBD patients. Studies on children under the age of 18 were excluded. Only population-based studies were included. All risk factors for osteoporosis and low BMD investigated in any included article were considered. Study quality and the possibility of bias were analysed using the Newcastle-Ottawa scale.

Research results

Twelve studies including 3661 IBD patients and 12789 healthy controls were included. Prevalence of osteoporosis varied between 4%-9% in studies including both CD and UC patients; 2%-9% in studies including UC patients, and 7%-15% in studies including CD patients. Among healthy controls, prevalence of osteoporosis was 3% and 10% in two studies. CD diagnosis, low body mass index (BMI) and low body weight were risk factors associated with osteoporosis or low BMD. Two out of four studies investigating gender found an association between female gender and lower BMD. CD patients had an increased risk for osteoporosis or low BMD over time, while UC patients did not. Increased age was associated with decreased BMD, and there was a positive association between weight and BMI and BMD over time. Great heterogeneity was found in the included studies in terms of study methodologies, definitions and the assessment of osteoporosis, and only a small number of population-based studies was available.

Research conclusions

This systematic review found a possible increase of prevalence of osteoporosis in CD cohorts when compared to UC and cohorts including both disease types. Lower weight and lower BMI were predictors of osteoporosis or low BMD in IBD patients. The results varied considerably between studies. Firm conclusions are difficult to draw due to considerable heterogeneity in terms of study methodologies, definitions and the assessment of osteoporosis, and the small number of population-based studies.

Research perspectives

Osteoporosis is a common disease that is associated with great economic and psychological burden worldwide due to the consequences of the disease in terms of osteoporotic fractures. Given the importance of adequate screening and treatment of osteoporosis, there is a need for more prospective population-based research on the relationship between osteoporosis and IBD-patients and subgroups in this population. Any such future studies should assess CD and UC separately, should include healthy subjects as controls, and should assess disease specific risk factors such as gut inflammation markers.