gastrins and Osteoporosis

Proton pump inhibitors (PPI) are one of the most widely used groups of drugs and their potential toxicity is periodically reviewed, emphasizing aspects originally considered secondary. The present review analyzes the physiological and pharmacological bases and the scarce clinical evidence for a potential association between the continued administration of PPI and the development of osteoporosis and bone fractures. Both disorders are clearly related to calcium homeostasis and are highly important in elderly patients due to their poor general prognosis and disabling consequences.

Topics: Achlorhydria; Aging; Calcium; Calcium, Dietary; Comorbidity; Disease Susceptibility; Fractures, Spontaneous; Gastric Acid; Gastrins; Homeostasis; Humans; Hyperparathyroidism, Secondary; Intestinal Absorption; Malabsorption Syndromes; Models, Biological; Osteoporosis; Proton Pump Inhibitors; Risk

Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linked with bariatric surgery outcomes, gastric production of these peptides was not elucidated before.. The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass.. Physiology Research Lab at the University.. Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 β, ER-α agonist, ER-β agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemical measurements, while histopathologic examination was performed in gastric and femur samples.. In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrin-expressing cells, ameliorated gastric injury, and improved bone loss.. SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications.

Topics: Animals; Estrogens; Female; Gastrectomy; Gastric Stump; Gastrins; Leptin; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Receptors, Estrogen

Multiple studies have reported an association between proton pump inhibitor (PPI) use and fracture. However, the causality of this association is questionable, as there is not a well defined mechanism of action, nor is there evidence of an effect on PPIs on areal bone mineral density (aBMD) using dual photon X-ray absorptiometry (DXA). It is possible that PPIs may induce changes in bone structure which would predispose to fracture in the absence of changes in aBMD. We used three-dimensional quantitative computed tomography (3D-QCT) imaging to determine if long-term PPI use was associated with structural changes in bone independent of aBMD.. We enrolled a sample of long-term (≥5 years) PPI users matched to a similar cohort of persons with no PPI use in the previous 5 years. All subjects underwent assessment of aBMD using DXA, volumetric BMD using 3D-QCT, as well as markers of bone metabolism. Measures of bone strength, including buckling ratio and section modulus, were also compared between the two samples.. 104 subjects were enrolled (52 PPI users and 52 PPI non-users). There were no differences detected in standard BMD, volumetric BMD, markers of bone metabolism or measures of bone strength between the two groups.. Long-term PPI use is not associated with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture. These findings provide further evidence that the association between PPI use and fracture is not causal.

Topics: Absorptiometry, Photon; Aged; Alkaline Phosphatase; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Calcium; Cohort Studies; Collagen Type I; Female; Femur Neck; Gastrins; Humans; Imaging, Three-Dimensional; Linear Models; Magnesium; Male; Manitoba; Middle Aged; Multivariate Analysis; Osteocalcin; Osteoporosis; Parathyroid Hormone; Peptides; Phosphates; Proton Pump Inhibitors; Time Factors; Tomography, X-Ray Computed; Vitamin D

Epidemiological studies suggest an increased fracture risk in patients taking proton pump inhibitors (PPIs) for long term. The underlying mechanism, however, has been disputed. By binding to the gastric proton pump, PPIs inhibit gastric acid secretion. We have previously shown that proton pump (H(+)/K(+)ATPase beta subunit) KO mice exhibit reduced bone mineral density (BMD) and inferior bone strength compared with WT mice. Patients using PPIs as well as these KO mice exhibit gastric hypoacidity, and subsequently increased serum concentrations of the hormone gastrin. In this study, we wanted to examine whether inhibition of the gastrin/CCK2 receptor influences bone quality in these mice. KO and WT mice were given either the gastrin/CCK2 receptor antagonist netazepide dissolved in polyethylene glycol (PEG) or only PEG for 1year. We found significantly lower bone mineral content and BMD, as well as inferior bone microarchitecture in KO mice compared with WT. Biomechanical properties by three-point bending test also proved inferior in KO mice. KO mice receiving netazepide exhibited significantly higher cortical thickness, cortical area fraction, trabecular thickness and trabecular BMD by micro-CT compared with the control group. Three-point bending test also showed higher Young's modulus of elasticity in the netazepide KO group compared with control mice. In conclusion, we observed that the gastrin receptor antagonist netazepide slightly improved bone quality in this mouse model, suggesting that hypergastrinemia may contribute to deteriorated bone quality during acid inhibition.

Topics: Absorptiometry, Photon; Adaptor Proteins, Signal Transducing; Animals; Benzodiazepinones; Bone and Bones; Bone Density; Drug Evaluation, Preclinical; Female; Gastrins; Glycoproteins; H(+)-K(+)-Exchanging ATPase; Intercellular Signaling Peptides and Proteins; Leptin; Mice, Inbred BALB C; Mice, Knockout; Osteocalcin; Osteoporosis; Phenylurea Compounds; Proton Pump Inhibitors; RANK Ligand; Receptor, Cholecystokinin B; Stomach; X-Ray Microtomography

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.. 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.. 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.. 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.

Topics: Animals; Anti-Ulcer Agents; Biomechanical Phenomena; Bone and Bones; Bone Density; Calcification, Physiologic; Cartilage; Cholecystokinin; Diet; Femur; Gastrins; Ketoglutaric Acids; Male; Omeprazole; Organ Size; Osteoporosis; Rats; Rats, Sprague-Dawley; Tibia

Data on risk factors for bone loss in chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC) are scanty and/or conflicting.. Bone mineral density (BMD) in the distal forearm was measured using single-photon absorptiometry in 39 patients with CAH and 32 patients with PBC. We also attempted to identify risk factors for bone loss by means of a questionnaire and through a wide range of biochemical analyses.. In the CAH patients BMD is inversely related to the duration of steroid treatment and to age at menarche. In the PBC patients there was a strong correlation between BMD and serum gastrin concentrations.. Bone loss in CAH is to some extent explained by steroid treatment and delayed menarche. Bone loss in PBC may be reduced by increased calcitonin secretion induced by gastrocalcin.

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Bone Density; Diet; Female; Gastrins; Hepatitis C; Hepatitis, Chronic; Humans; Liver Cirrhosis, Biliary; Male; Menarche; Middle Aged; Osteoporosis; Radionuclide Imaging; Risk Factors

Topics: Afferent Loop Syndrome; Anemia, Macrocytic; Diarrhea; Dumping Syndrome; Folic Acid Deficiency; Gastrectomy; Gastric Juice; Gastrins; Humans; Intestinal Absorption; Intrinsic Factor; Mucus; Osteoporosis; Postgastrectomy Syndromes; Stomach Neoplasms; Vitamin B 12 Deficiency; Vomiting