Correlation between in vitro and in vivo data on food digestion. What can we predict with static in vitro digestion models?

During the last decade, there has been a growing interest in understanding food's digestive fate in order to strengthen the possible effects of food on human health. Ideally, food digestion should be studied in vivo on humans but this is not always ethically and financially possible. Therefore, simple in vitro digestion models mimicking the gastrointestinal tract have been proposed as alternatives to in vivo experiments. Thus, it is no surprise that these models are increasingly used by the scientific community, although their various limitations to fully mirror the complexity of the digestive tract. Therefore, the objective of this article was to call upon the collective experiences of scientists involved in Infogest (an international network on food digestion) to review and reflect on the applications of in vitro digestion models, the parameters assessed in such studies and the physiological relevance of the data generated when compared to in vivo data. The authors provide a comprehensive review in vitro and in vivo digestion studies investigating the digestion of macronutrients (i.e., proteins, lipids, and carbohydrates) as well as studies of the bioaccessibility and bioavailability of micronutrients and phytochemicals. The main conclusion is that evidences show that despite the simplicity of in vitro models they are often very useful in predicting outcomes of the digestion in vivo. However, this has relies on the complexity of in vitro models and their tuning toward answering specific questions related to human digestion physiology, which leaves a vast room for future studies and improvements.

Evidence of a parathyroid hormone-independent chronic effect of estrogen on renal phosphate handling and sodium-dependent phosphate cotransporter type IIa expression.

The effects of estrogen on phosphate metabolism are not well understood. To better define the chronic effects of estrogen on phosphate balance and on renal phosphate handling, the following groups were examined: A. young male and female rats, age- and weight-matched (age 8-10 weeks, 1 (st) study), and B. ovariectomized female rats (OVX), 22 weeks old, ovariectomized aged-matched rats receiving estrogen replacement (15 micromol x 3/week) for 14 weeks (OVX+E), control female rats (intact ovaries), and male rats, both age matched to OVX and OVX+E (2 (nd) Study). In younger females (1 (st) study), plasma phosphate was lower, whereas the urinary excretion of phosphate was higher than in males. In adult intact females and in OVX+E urinary excretion of phosphate was higher than in males and OVX (2 (nd) Study). In these rats, a significant correlation between plasma phosphate and estrogen level was found. Sodium-dependent phosphate cotransporter (NaPiIIa) mRNA expression and protein abundance were higher in the renal cortex of younger male rats than in age- and weight-matched females. In adult rats, NaPiIIa mRNA and protein abundance were higher in OVX than in OVX+E, and in mature males as compared with age-matched females. These differences were not related to the parathyroid hormone (PTH) levels. Chronic estrogen administration was also associated with increased plasma calcium level and urinary calcium excretion. These results suggest that chronic estrogen treatment is associated with an inhibitory, PTH-independent effect on the expression of NaPiIIa in the kidney, leading to sex-related differences in phosphate balance.

Treatment of osteoporotic ovariectomized rats with 24,25(OH)2D3.

BACKGROUND: Antiresorptive therapeutic regimens are the mainstay of current management of osteoporosis. Treatments that are promoting new bone formation are less available and less affordable. Previous studies have suggested that 24,25(OH)(2)D(3) could enhance bone formation. The effect of 24,25(OH)(2)D(3) on bone formation in ovariectomized osteopenic rats (OVX) was evaluated in this study. MATERIALS AND METHODS: Mature Sabra rats were divided into two groups: sham-operated and OVX. Three months after surgery the OVX and sham-operated rats were divided into the following subgroups: (1) sham rats injected with vehicle, (2) sham rats injected with 24,25(OH)(2)D(3), (3) OVX rats injected with vehicle, and (4) OVX rats injected with 24,25(OH)(2)D(3). After 2 weeks' treatment, histomorphometry of the right tibiae was performed. RESULTS: Ovariectomy resulted in a decrease in total bone volume (TBV/TV) and in bone formation (BFR/BS), P < 0.005 and P < 0.05 respectively, when compared with the sham-operated rats. Beside the decrease in TBV and BFR, the OVX rats showed an increase in osteoclastic bone resorption (P < 0.001 vs. sham). Administration of 24,25(OH)(2)D(3) was followed by an increase in all static and dynamic bone-forming parameters. The TBV/BV (P < 0.025), osteoblast surface (Ob.S/BS) (P < 0.001), as well as the BFR/BS (P < 0.005), increased in the OVX-treated group when compared with the OVX-untreated and sham-operated rats. This increment in bone formation was associated with a decrease in bone resorption (P < 0.001 in OVX-treated vs. OVX-untreated rats). CONCLUSIONS: This study shows that 24,25(OH)(2)D(3) may be of benefit in experimental osteopenia following ovariectomy, both by suppressing osteoclastic hyperactivity and by stimulating bone formation.

New worldwide trends in presentation of renal osteodystrophy and its relationship to parathyroid hormone levels.

AIMS: Abnormal mineral metabolism in chronic renal disease is associated with bone disease and extraskeletal calcifications. High turnover, hyperparathyroid bone disease, the most common form of renal osteodystrophy, has been the target for aggressive therapy. More recently, an increasing occurrence of low turnover bone disease has been reported. The present study was undertaken to evaluate the current prevalence of different forms of bone disease in a large population on chronic hemodialysis and its relationship to parathyroid hormone (PTH) levels. METHODS: Ninety-six chronic hemodialysis patients underwent double tetracycline-labeled bone biopsy. Serum PTH levels were obtained in 52 patients at the time of biopsy. Bone formation rate (BFR/BS) was plotted vs. PTH levels in all patients and in subgroups with PTH ranges between 0-150, 150-500 and 500 - 1,200 pg/ml. RESULTS: The histomorphometric data showed that 40% of all patients were affected by osteitis fibrosa cystica (OFC). In the remaining 60%, various forms of low-turnover bone disease were observed. There was no correlation between PTH and BFR/BS in all patients (r = 0.28) and in subgroups whose PTH levels ranged between 150 - 500 and 500 - 1,200 pg/ml (r = 0.027, r = 0.21), respectively. A close correlation between PTH and BFR/BS (r = 0.84, p < 0.05) was found only in the subgroup with a PTH level ranging low-turnover bone disease. The predictive between 0 - 150 pg/ml. CONCLUSIONS: The histomorphometric findings present a wide spectrum of renal osteodystrophy with a shift towardsvalue of PTH is limited as high-turnover osteodystrophy may present with low PTH levels and that with low turnover may occur with high PTH levels. In the latter parathyroidectomy should be avoided. We share the view that bone biopsy remains the "gold standard" diagnostic tool for renal osteodystrophy.

Stimulation of osteoclastic bone resorption in a model of glycerol-induced acute renal failure: evidence for a parathyroid hormone-independent mechanism.

This study was undertaken to evaluate the bone changes occurring in rats with acute renal failure (ARF). Acute renal failure was induced in rats 24 hours after dehydration by an intramuscular injection of glycerol. After induction of ARF, the rats were divided into two groups, one of which underwent parathyroidectomy (PTX). Rats with normal renal function, matched for age and weight, were used as controls and divided into two groups, one of them for PTX. At termination of the study blood and urine chemistry and bone histomorphometry were analyzed. Rats with glycerol-induced ARF developed bone changes compatible with mild hyperparathyroid bone disease, characterized mainly by increased osteoclastic bone resorption when compared with control rats having normal renal function. Rats with normal renal function following PTX developed bone disease showing complete suppression of forming and resorptive parameters. Rats with glycerol-induced ARF and PTX showed abolishment of all bone forming parameters, but a dramatic increase in osteoclastic resorption was apparent. Based on these observations we suggest that, in this model of glycerol-induced ARF, osteoclastic bone resorption may develop in the absence of parathyroid hormone, probably stimulated by other potent osteoclastogenic factors.

24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3 ameliorates renal osteodystrophy in rats with chronic renal failure.

AIMS: This study compares the effects of 1,25(OH)2D3 and 24,25(OH)2D3 alone or in combination on renal osteodystrophy in rats with chronic renal failure (CRF). MATERIAL AND METHOD: One month subsequent to 5/6 nephrectomy animals were divided into four groups and treated for one or four weeks with either vehicle, 1,25(OH)2D3, 24,25(OH)2D3 or 1,25(OH)2D3 + 24,25(OH)2D3. A sham-operated group with normal renal function matched for age and weight was used as control. At the termination of the study blood chemistry, parathyroid hormone (PTH) level and bone histomorphometry were analyzed. RESULTS: The main findings were: amelioration of 1,25(OH)2D3-induced hypercalcemia by 24,25(OH)2D3, and similar suppression of PTH by the two metabolites of vitamin D when administered alone or in combination. Bone histomorphometry showed that 1,25(OH)2D3 alone exerts a potent proliferative effect on the osteoblasts but severely depresses their mineralizing capacity in a dose- and time-dependent manner. By contrast, 24,25(OH)2D3 improved the mineralizing activity with only a limited effect on osteoblast proliferation. Addition of 24,25(OH)2D3 potentiated the beneficial effect of 1,25(OH)2D3 on bone-resorbing parameters and corrected the mineralization failure. CONCLUSIONS: Based on the above observations we suggest that the combined treatment with 1,25(OH)2D3 and 24,25(OH)2D3 markedly improves the morphologic and metabolic abnormalities of renal osteodystrophy.

Renal osteodystrophy in rats with reduced renal mass.

The rat remnant kidney, a popular model of experimental renal failure, has also been used to assess the histological bone changes associated with reduction in renal mass. The suitability of this model has been challenged, especially with regard to the standardization of animals from different age groups and various degrees of renal failure. The present study was undertaken: (1) to better evaluate the histomorphometric changes associated with reduction in renal mass; (2) to assess these changes over a longer follow-up period as compared to those of matched intact animals; (3) to define the response to pharmacological doses of calcitriol. Male rats were evaluated 4 and 8 weeks after induction of renal failure (5/6 nephrectomy) and compared with age-matched control rats with intact kidneys. Plasma biochemistry, creatinine clearance and parathyroid hormone (PTH) were obtained from normal rats and from the rats with chronic renal insufficiency. Histomorphometric studies were performed in all animals on the right tibial bone. Induction of renal failure of 4 weeks' duration (short-term study, age 16 weeks) was associated with increased PTH and bone resorption, but suppressed bone formation. At long-term follow-up (rats aged 20 weeks), the suppression in bone formation was even more prominent. These changes were assessed considering normal bone histomorphometry during the process of growing. Calcitriol administration was associated with a significant suppression of bone resorption and a spectacular increase in all osteoid parameters. The bone formation rate, however, remained in the same low range as that in untreated animals. This model of renal osteodystrophy is similar to human secondary hyperparathyroidism with regard to the enhanced bone resorption, but differs by the marked decrease in bone formation. There was a remarkable similarity between the response of rats with renal failure and that of patients with severe secondary hyperparathyroidism to large doses of calcitriol, leading in both to adynamic bone disease. Keeping in mind the species differences, the bone changes developing in the uraemic rats may be useful in understanding certain aspects of human renal osteodystrophy.