A dairy product fermented by lactobacilli cancels the adverse effects of hypochlorhydria induced by a proton pump inhibitor on bone metabolism in growing rats

Abstract

The purpose of the present study is to investigate the effects of hypochlorhydria induced by proton pump inhibitor (PPI) administration and intake of a dairy product fermented by lactobacilli (DFL) on bone metabolism in growing rats. Male rats, aged 3 weeks, were divided into two groups: a control group fed a casein-based diet and a group fed a DFL-based diet. Each group was fed its respective experimental diets for 9 d. At day 5 of the feeding period, each group was divided into two subgroups: one that received a saline injection and one that received a PPI injection. Rats were subcutaneously administered saline or PPI for 5 d. Faecal Ca excretion was determined from day 6 to day 9. At the end of the experiment, plasma and femurs were collected. Administration of PPI significantly decreased bone mineral density (shown by X-ray computerised tomography) and bone strength (shown by a three-point bending test) in the control group. Plasma osteocalcin, type I collagen C-telopeptides, 1,25-dihydroxyvitamin D and parathyroid hormone concentrations were elevated by PPI administration in the control group. Faecal Ca excretion and urinary P excretion in the control group were remarkably increased by PPI administration. On the other hand, these adverse effects of PPI were not observed in the DFL group. These results suggest that hypochlorhydria-induced bone loss may result from high bone turnover induced by secondary hyperparathyroidism due to Ca malabsorption and that DFL intake cancels these adverse effects probably via improving Ca malabsorption in growing rats.Key words: Hypochlorhydria: Fermented milk: Bone: Calcium Most physiological functions decline progressively with age. Gastric acid secretion also decreases with advancing age in humans (1) and rats (2,3) . Recently, Aoki et al. reported that chronic atrophic gastritis, a factor of hypochlorhydria, is very common among the elderly (4) .There are some studies suggesting the association between hypochlorhydria and bone loss. Many researchers have reported that gastrectomy induces bone loss in rats (5 -8) and human subjects (9 -12) . However, gastrectomy in itself has multiple risk factors other than hypochlorhydria for bone loss. For example, the production of the stomach hormone ghrelin, which is involved in bone physiology, is suppressed by gastrectomy (13) . Some studies have shown that the use of proton pump inhibitors (PPI), the most potent acid-suppressing drugs, is associated with an increased risk of hip fracture (14,15) . However, there is limited research showing the effects of hypochlorhydria induced by PPI on bone metabolism in human subjects or animals.The absorbability of Ca is dependent on its solubility. The acidity in the stomach and resulting chyme increases Ca solubility (16) . Thus, hypochlorhydria is considered to have a potential adverse effect on bone metabolism via the inhibition of Ca absorption.The usefulness of cows' milk (17,18) or dairy products including cows' milk and yogurt (19) for the prevention of osteoporosis has been ...

Effects of Proton Pump Inhibitor Administration and Intake of a Combination of Yogurt and Galactooligosaccharides on Bone and Mineral Metabolism in Rats

“…We found that PPI administration did not alter calcium absorption in adult rats, while the previous studies have shown that it decreased calcium absorption in weaning rats [7,8], suggesting that the effects of PPI administration on calcium absorption depend on age. Calcium absorption occurs by both an active saturable transcellular pathway and a passive non-saturable paracellular pathway, and 1,25(OH) 2 D is the major stimulator of an active transcellular pathway [17,19].…”

“…In contrast, we have previously shown that PPI administration decreased calcium absorption and did not affect phosphorus absorption in weaning rats, although it increased 1,25(OH) 2 D levels [7], which suggests that high 1,25(OH) 2 D levels induced by PPI administration did not compensate for the decreased calcium absorption in weaning rats. Calcium absorption occurs by both an active saturable transcellular pathway and a passive non-saturable paracellular pathway [17,19].…”

“…In weaning rats, PPI administration decreased calcium absorption, followed by the increase in bone resorption, leading to the decrease in BMD [7]. In contrast, PPI administration did not affect calcium absorption in adult rats, although it decreased BMD.…”

“…The assumed mechanism is that PPI use decreases calcium absorption, subsequently leading to lower bone mass [6]. In fact, we have previously reported that PPI administration decreased calcium absorption, which resulted in decreased bone mineral density (BMD) and bone strength in weaning rats [7,8]. …”

Gut Function-Enhancing Properties and Metabolic Effects of Dietary Indigestible Sugars in Rodents and Rabbits

“…Both the distal femur, trabecular volumetric bone mineral density, and proximal tibia volumetric bone mineral density increased with GOS supplementation, too [ 87 ]. Feeding of GOS for 9 days to growing rats with hypochlorhydria significantly improved apparent absorption of Ca, Mg and Fe [ 82 , 88 ]. In particular, the effect was stronger when GOS ingestion was combined with a dairy product fermented by Lactobacilli , resulting in improved Ca, P, Fe and Zn retention during the mineral balance test in rats [ 88 ].…”