Osteoporosis Complications in Crohn's Disease Patients: Factors, Pathogenesis, and Treatment Outlines

Baban, Yaqot N; Edicheria, Christopher M; Joseph, Joseph; Kaur, Parneet; Mostafa, Jihan A

doi:10.7759/cureus.20564

Cited by 4 publications

(5 citation statements)

References 44 publications

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“…Previously, we found that a dysregulated pro-inflammatory cytokine level caused by MAP infection results in an extraintestinal manifestation characterized by hyperactive osteoclast activity, which eventually affects bone biomarker levels such as osteocalcin and calcium among CD patients [26]. Additionally, the prevalence of osteoporosis is higher among inflammatory bowel disease patients in general, and some relatively young patients have been diagnosed with severe cases of bone disorders [27].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis

Talafha,

Qasem,

Naser

2024

Nutrients

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Background: Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. CYP27B1 encodes a member of the cytochrome P450 superfamily of enzymes. It is instrumental in the conversion of circulating vitamin D (calcifediol) to active vitamin D (calcitriol). This is a crucial step for macrophages to express Cathelicidin Anti-microbial Peptide (CAMP), an anti-bacterial factor released during the immune response. Our recent study indicated that a Crohn’s disease (CD)-associated pathogen known as Mycobacterium avium paratuberculosis (MAP) decreases vitamin D activation in macrophages, thereby impeding cathelicidin production and MAP infection clearance. The mechanism by which MAP infection exerts these effects on the vitamin D metabolic axis remains elusive. Methods: We used two cell culture models of THP-1 macrophages and Caco-2 monolayers to establish the effects of MAP infection on the vitamin D metabolic axis. We also tested the effects of Calcifediol, Calcitriol, and SB203580 treatments on the relative expression of the vitamin D metabolic genes, oxidative stress biomarkers, and inflammatory cytokines profile. Results: In this study, we found that MAP infection interferes with vitamin D activation inside THP-1 macrophages by reducing levels of CYP27B1 and vitamin D receptor (VDR) gene expression via interaction with the TLR2-dependent p38/MAPK pathway. MAP infection exerts its effects in a time-dependent manner, with the maximal inhibition observed at 24 h post-infection. We also demonstrated the necessity to have toll-like receptor 2 (TLR2) for MAP infection to influence CYP27B1 and CAMP expression, as TLR2 gene knockdown resulted in an average increase of 7.78 ± 0.88 and 13.90 ± 3.5 folds in their expression, respectively. MAP infection also clearly decreased the levels of p38 phosphorylation and showed dependency on the p38/MAPK pathway to influence the expression of CYP27B1, VDR, and CAMP which was evident by the average fold increase of 1.93 ± 0.28, 1.86 ± 0.27, and 6.34 ± 0.51 in their expression, respectively, following p38 antagonism. Finally, we showed that calcitriol treatment and p38/MAPK blockade reduce cellular oxidative stress and inflammatory markers in Caco-2 monolayers following macrophage-mediated MAP infection. Conclusions: This study characterized the primary mechanism by which MAP infection leads to diminished levels of active vitamin D and cathelicidin in CD patients, which may explain the exacerbated vitamin D deficiency state in these cases.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis

Talafha,

Qasem,

Naser

2024

Nutrients

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“…Loss of protein, loss of muscle mass due to steroids, poor diet, and poor absorption of nutrients cause weight loss and malnutrition [7,9,18]. Insufficient intake and poor absorption of calcium, deficiency of vitamin D, reduced physical activity, inflammation, long term corticosteroids result in decreased bone formation and mineralization [19]. Our patient was diagnosed with low bone density and osteoporosis, so regular diagnostic monitoring with DEXA (dual-energy x-ray absorptiometry) was introduced.…”

Section: Case Reportmentioning

confidence: 96%

“…Extraintestinal symptoms and signs are ulcers or sores in the mouth [18], osteoporosis is more common [19], due to inflammation, impaired absorption of iron from the small intestine (malabsorption), and recurrent bleeding. Anemia is often present.…”

Section: Case Reportmentioning

confidence: 99%

Perspectives in the Treatment of Crohn's Disease by a Physician of Family Medicine: A Clinical Case Presentation

Luka¹,

Eva²,

Igor³

et al. 2022

Clin Med Rev Case Rep

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Background: Crohn's disease is a rare disease with a chronic relapsing course. Usually begins at a young age influenced by environmental, genetic, and immunological factors. Patients mostly have only intestinal changes. In addition to the gut, other organs, such as skin, joints, liver, and kidneys can be affected. The type of treatment and choice of drugs depends on the type and severity of the disease.Objective: Managing a patient with Crohn's disease requires an individual and holistic approach to treatment by a family physician complemented with good cooperation with gastroenterologists and other clinical specialists. In the process of long-term care family physician provides psychosocial support to the patient in overcoming the disease.Discussion: Here we describe the details of a case with a review of the literature. Based on history taking, physical examination, and investigation, the patient was diagnosed with Crohn's disease.

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“…TNF-α blockade improves bone formation and reduces bone resorption by suppressing T cells [16,17]. Infliximab maintenance therapy also leads to about a 14% increase in lumbar bone density [18,19]. The Swiss IBD cohort study (SIBDCS), launched in 2006 with the aim of enrolling and following patients with IBD throughout Switzerland [20], demonstrated that early administration of anti-TNF-α was associated with a lower osteoporosis risk.…”

Section: Pathophysiology Of Inflammatory Bowel Disease-associated Bon...mentioning

confidence: 99%

Bone health in patients with inflammatory bowel disease

Kreienbuehl,

Rogler,

Emanuel

et al. 2024

Swiss Med Wkly

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Patients with inflammatory bowel disease (IBD) are prone to reduced bone mineral density and elevated overall fracture risk. Osteopenia affects up to 40% of patients with IBD (high regional variability). Besides disease activity, IBD specialists must consider possible side effects of medication and the presence of associated diseases and extraintestinal manifestations. Osteopenia and osteoporosis remain frequent problems in patients with IBD and are often underestimated because of widely differing screening and treatment practices. Malnutrition, chronic intestinal inflammation and corticosteroid intake are the major pathophysiological factors contributing to osteoporosis. Patients with IBD are screened for osteoporosis using dual-energy X-ray absorptiometry (DXA), which is recommended for all patients with a prolonged disease course of more than three months, with repeated corticosteroid administration, aged >40 years with a high FRAX risk score or aged <40 years with multiple risk factors. From a therapeutic perspective, besides good disease control, vitamin D supplementation and glucocorticoid sparing, several specific osteological options are available: bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab), parathyroid hormone (PTH) analogues and selective estrogen receptor modulators. This review provides an overview of the pathophysiology, diagnosis, prevention and treatment of IBD-associated bone loss.

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Osteoporosis Complications in Crohn's Disease Patients: Factors, Pathogenesis, and Treatment Outlines

Cited by 4 publications

References 44 publications

Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis

Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis

Perspectives in the Treatment of Crohn's Disease by a Physician of Family Medicine: A Clinical Case Presentation

Bone health in patients with inflammatory bowel disease

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