Inflammatory Bowel Disease: Effects on Bone and Mechanisms

Sylvester, Francisco

doi:10.1007/978-3-319-66653-2_7

Cited by 28 publications

(26 citation statements)

References 120 publications

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“…It is now clear that changes in the gut microbiota can impact bone density and health . For example, intestinal infection with pathogenic bacteria can induce bone loss in male mice .…”

Section: Introductionmentioning

confidence: 99%

“…(49) It is now clear that changes in the gut microbiota can impact bone density and health. (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69) For example, intestinal infection with pathogenic bacteria can induce bone loss in male mice. (70) In contrast, treatment with beneficial bacteria (probiotics) alters gut microbiota composition (50,(53)(54)(55)57,(71)(72)(73)(74) and enhances bone density in healthy male mice, (53) post-antibiotic treated male mice, (68) ovariectomized mice, (50,54,55) inflamed intact female mice, (75) and type 1 diabetic male mice.…”

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confidence: 99%

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Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

123

119

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Glucocorticoids (GCs) are potent immune‐modulating drugs with significant side effects, including glucocorticoid‐induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC‐Tx) in the presence or absence of broad‐spectrum antibiotic treatment (ABX) to deplete the microbiota. Long‐term ABX prevented GC‐Tx‐induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC‐Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC‐Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC‐Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4‐fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC‐Tx–induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC‐Tx–induced osteoblast and osteocyte apoptosis. GC‐Tx suppression of Wnt10b in bone was restored by the LR and high‐molecular‐weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone‐specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.

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“…It is now clear that changes in the gut microbiota can impact bone density and health . For example, intestinal infection with pathogenic bacteria can induce bone loss in male mice .…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Schepper

Collins

Rios‐Arce

et al. 2019

Journal of Bone and Mineral Research

123

119

View full text Add to dashboard Cite

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“…Decreased bone mineral density (BMD) is an important extraintestinal complication of paediatric inflammatory bowel disease (IBD) . Almost 50% of children and adolescents with IBD have a BMD z‐score of <−1 and about 25% have a BMD z‐score <−2 .…”

Section: Introductionmentioning

confidence: 99%

“…A number of factors contribute to impaired BMD in IBD patients. These include: inflammatory cytokines, glucocorticoid treatment, malnutrition, low calcium intake, vitamin D deficiency, decreased activity, hypogonadism, decreased skeletal muscle mass and possibly dysbiotic intestinal microbial flora …”

Section: Introductionmentioning

confidence: 99%

Longitudinal changes in bone mineral density in children with inflammatory bowel diseases

et al. 2019

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Decreased bone mineral density (BMD) is an important extraintestinal complication of paediatric inflammatory bowel disease (IBD). 1 Almost 50% of children and adolescents with IBD have a BMD zscore of <−1 and about 25% have a BMD z-score <−2. 2 Children with IBD may have an increased risk for fractures during childhood, especially vertebral fractures. 3 Peak bone mass is reached by the third decade of life. Thus, children with IBD are at risk of failing to reach their optimal peak bone mass, and of having a higher incidence of fractures later, during adulthood. 4 A number of factors contribute to impaired BMD in IBD patients.These include: inflammatory cytokines, 5 glucocorticoid treatment, 6 malnutrition, 7 low calcium intake, vitamin D deficiency, 6 decreased Abbreviations: BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; IBD, inflammatory bowel disease; SDS, standard deviation score; TBLH, total body less head. Abstract Aim: Children with inflammatory bowel disease (IBD) are prone to low bone mineral density (BMD). Our aim was to assess longitudinal changes in BMD in this population. Methods: A retrospective longitudinal study of children with IBD, treated at two tertiary centres in Israel, who underwent two BMD measurements by dual-energy X-ray absorptiometry (DXA). Changes in lumbar spine BMD (∆L1-4 z-scores) were examined for correlations with clinical characteristics. Results: The cohort included 41 patients (age at diagnosis 12.1 ± 3.5 years, 23 females).The mean interval between the scans was 3.4 ± 2.0 years. There was a trend towards improvement in L1-4 z-scores (−1.64 ± 1.02 vs −1.45 ± 0.83, P = .12). ∆L1-4 z-scores correlated positively with ∆weight-standard deviation scores (SDS), ∆height-SDS and ∆BMI-SDS, and with age at the second scan (R = .55, P < .01; R = .42, P < .01; R = .42, P = .01; R = .35, P = .02, respectively); and negatively with L1-4 z-scores at the first scan (R = −.63, P < .01). Stepwise linear regression analysis identified the first scan L1-4 z-scores and ∆weight-SDS as independent predictors of ∆L1-4 z-scores. An L1-4 z-score ≤−2 at the first DXA scan was associated with significant improvement at the second scan.Conclusion: Improvement in BMD was more pronounced in children who gained weight or whose BMD was low at the first scan. K E Y W O R D S bone, bone mineral density, Crohn's disease, dual-energy X-ray absorptiometry, ulcerative colitis | 1027 LEVY-SHRAGA Et AL. activity, hypogonadism, decreased skeletal muscle mass 1 and possibly dysbiotic intestinal microbial flora. 8Only limited longitudinal data are available regarding changes in BMD in the course of IBD. Some studies in paediatric 9,10 and adult patients 11,12 found no significant changes in BMD z-scores during follow-up, despite clinical disease remission. However, others reported improvement with time. 13,14 The aim of our study was to examine longitudinal changes in BMD of children and adolescents with IBD, and associations of such changes with anthropometric parameters and disease activity.

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“…However, they would not have been detected by this panel analysis, since only coding exons were screened. Besides the impact of genetics, additionally, deteriorating factors include an insufficient enteral calcium resorption (e.g., vitamin D deficiency [28], inflammatory bowel diseases [29]), drug side effects (e.g., steroids [30], proton pump inhibitors [31]), or immobilization [7], which possibly overburden the bone microarchitecture. A similar phenomenon is the first manifestation of a mild maturity-onset diabetes of the young (MODY) type 2 as gestational diabetes [32].…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis uncovers monogenic bone disorders in women with pregnancy-associated osteoporosis: three novel mutations in LRP5, COL1A1, and COL1A2

et al. 2018

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Our data show that previously unrecognized monogenic bone disorders play an important role in PAO. Pregnancy should be considered a skeletal risk factor, which can promote the initial clinical onset of such skeletal disorders. The underlying increased calcium demand is essential in terms of prophylactic and therapeutic measures, which are especially required in individuals with a genetically determined low bone mass. The implementation of this knowledge in clinical practice can enable the partial recovery of the skeleton. Consistent genetic studies are needed to analyze the frequency of pathogenic variants in women with PAO.

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Inflammatory Bowel Disease: Effects on Bone and Mechanisms

Cited by 28 publications

References 120 publications

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis

Longitudinal changes in bone mineral density in children with inflammatory bowel diseases

Mutational analysis uncovers monogenic bone disorders in women with pregnancy-associated osteoporosis: three novel mutations in LRP5, COL1A1, and COL1A2

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