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Infection by CagA-Positive Helicobacter pylori Strains and Bone Fragility: A Prospective Cohort Study
Luigi Gennari1, Daniela Merlotti1, Natale Figura1
1Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
Insights
Helicobacter pylori (HP) infection, particularly CagA-positive strains, is linked to lower bone density and increased fracture risk in adults. This finding suggests HP may be a significant risk factor for osteoporosis and bone fragility.
Area of Science:
- Bone Biology and Metabolism
- Infectious Diseases
- Epidemiology
Background:
- Helicobacter pylori (HP) infection is a common cause of gastrointestinal issues and linked to extraintestinal conditions like osteoporosis.
- Previous research has not prospectively evaluated HP's impact on bone health and fracture incidence.
Purpose of the Study:
- To investigate the prospective association between Helicobacter pylori infection and bone mineral density (BMD) and fracture risk.
- To explore the role of CagA-positive HP strains in bone health outcomes.
Main Methods:
- A population-based cohort of 1149 adults was followed for up to 11 years.
- HP infection was assessed via serologic testing for HP antibodies and cytotoxin-associated gene-A (CagA).
- Bone mineral density (BMD) and incident fractures (vertebral and nonvertebral) were monitored.
Main Results:
- While overall HP prevalence did not differ by BMD, CagA-positive HP infection was more common in osteoporotic and osteopenic individuals.
- Higher anti-CagA antibody levels correlated with lower lumbar and femoral BMD.
- CagA-positive HP infection significantly increased the risk of vertebral fractures (HR 5.27) and nonvertebral fractures (HR 2.09).
- Reduced estrogen and ghrelin levels and impaired bone turnover were noted in CagA-positive HP carriers.
Conclusions:
- Helicobacter pylori infection, specifically by CagA-expressing strains, is identified as a potential risk factor for osteoporosis and fractures.
- The findings suggest a link between CagA-positive HP infection and compromised bone health, warranting further investigation into pathogenic mechanisms.
Abstract:
Helicobacter pylori (HP) infection is a common and persistent disorder acting as a major cofactor for the development of upper gastrointestinal diseases and several extraintestinal disorders including osteoporosis. However, no prospective study assessed the effects of HP on bone health and fracture risk. We performed a HP screening in a population-based cohort of 1149 adults followed prospectively for up to 11 years. The presence of HP infection was assessed by serologic testing for serum antibodies to HP and the cytotoxin associated gene-A (CagA). The prevalence of HP infection did not differ among individuals with normal bone mineral density (BMD), osteoporosis, and osteopenia. However, HP infection by CagA-positive strains was significantly increased in osteoporotic (30%) and osteopenic (26%) patients respect to subjects with normal BMD (21%). Moreover, anti-CagA antibody levels were significantly and negatively associated with lumbar and femoral BMD. Consistent with these associations, patients affected by CagA-positive strains had a more than fivefold increased risk to sustain a clinical vertebral fracture (HR 5.27; 95% CI, 2.23-12.63; p < .0001) and a double risk to sustain a nonvertebral incident fracture (HR 2.09; 95% CI, 1.27-2.46; p < .005). Reduced estrogen and ghrelin levels, together with an impaired bone turnover balance after the meal were also observed in carriers of CagA-positive HP infection. HP infection by strains expressing CagA may be considered a risk factor for osteoporosis and fractures. Further studies are required to clarify in more detail the underlying pathogenetic mechanisms of this association. © 2020 American Society for Bone and Mineral Research (ASBMR).
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