title: Can 2-oxoglutarate prevent changes in bone evoked by omeprazole?
abstract: OBJECTIVE
  Proton-pump inhibitors, such as omeprazole, are widely used in the prevention and treatment of gastroesophageal diseases. However, an association between proton-pump inhibitors and the increased risk of bone fractures has been observed, especially in patients treated for extended periods. Conversely, 2-oxoglutarate, a precursor of hydroxyproline, the most abundant amino acid in bone collagen, counteracts the bone loss. The aim of the present study was to elucidate the influence of omeprazole on bone and investigate whether dietary 2-oxoglutarate supplementation could prevent the effects of omeprazole.
  
  
  METHODS
  Eighteen male Sprague-Dawley rats were used. Rats received omeprazole in the diet and 2-oxoglutarate in the drinking water. Body and organ weights and serum concentrations of cholecystokinin and gastrin were measured. The femurs, tibias, and calvarias were collected. Histomorphometric analysis of bone and cartilage tissues was conducted. Bone densitometric and peripheral quantitative computed tomographic analyses of the femur and tibia were performed.
  
  
  RESULTS
  Omeprazole decreased the femur and tibia weights, the mechanical properties of the femur, the volumetric bone density and content, the trabecular and cortical bone mineral content, the total, trabecular, and cortical bone areas, the mean cortical thickness, and the periosteal circumference of the femur. Omeprazole had a minor effect on the examined bone morphology and exerted negligible effects on the cartilage. 2-Oxoglutarate lowered the gastrin concentration.
  
  
  CONCLUSIONS
  Omeprazole treatment exerts its effects mostly on bone mineralization and cancellous bone, adversely affecting bone properties. This adverse effect of omeprazole was not markedly abolished by 2-oxoglutaric acid, which acted as an anti-hypergastrinemic agent.
authors.affiliation: Department of Comparative Anatomy and Anthropology, Maria Curie-Sklodowska University, Lublin, Poland. piotr.dobrowolski@umcs.lublin.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Dobrowolski
authors.forename: Ewa
authors.initials: E
authors.lastname: Tomaszewska
authors.forename: Radoslaw P
authors.initials: RP
authors.lastname: Radzki
authors.forename: Marek
authors.initials: M
authors.lastname: Bienko
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wydrych
authors.forename: Adam
authors.initials: A
authors.lastname: Zdybel
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Pierzynowski
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D002113:Calcification, Physiologic; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D002766:Cholecystokinin / Q000097:blood; D004032:Diet; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D005755:Gastrins / Q000097:blood; D007656:Ketoglutaric Acids / Q000008:administration & dosage*; D008297:Male; D009853:Omeprazole / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000473:pathology
chemical_list: D000897:Anti-Ulcer Agents; D005755:Gastrins; D007656:Ketoglutaric Acids; D002766:Cholecystokinin; D009853:Omeprazole