Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro.

Silicon deficiency in animals leads to bone defects. This element may therefore play an important role in bone metabolism. Silicon is absorbed from the diet as orthosilicic acid and concentrations in plasma are 5-20 microM. The in vitro effects of orthosilicic acid (0-50 microM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1). Collagen type 1 mRNA expression and prolyl hydroxylase activity were also determined in the MG-63 cells. Alkaline phosphatase and osteocalcin (osteoblastic differentiation) were assessed both at the protein and the mRNA level in MG-63 cells treated with orthosilicic acid. Collagen type 1 synthesis increased in all treated cells at orthosilicic acid concentrations of 10 and 20 microM, although the effects were more marked in the clonal cell lines (MG-63, HCCl 1.75- and 1.8-fold, respectively, P < 0.001, compared to 1.45-fold in the primary cell lines). Treatment at 50 microM resulted in a smaller increase in collagen type 1 synthesis (MG-63 1.45-fold, P = 0.004). The effect of orthosilicic acid was abolished in the presence of prolyl hydroxylase inhibitors. No change in collagen type 1 mRNA level was seen in treated MG-63 cells. Alkaline phosphatase activity and osteocalcin were significantly increased (1.5, 1.2-fold at concentrations of 10 and 20 microM, respectively, P < 0.05). Gene expression of alkaline phosphatase and osteocalcin also increased significantly following treatment. In conclusion, orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.

Assessment of iron absorption from ferric trimaltol.

Therapeutic iron compounds have limited absorption and often have side-effects, which limits patient compliance. Iron trimaltol is a novel, stable complex, formed between ferric iron (Fe3+) and maltol (3-hydroxy-2-methyl-4-pyrone), and is effective in the treatment of iron deficiency anaemia with few side-effects. However, the kinetics of iron absorption from ferric trimaltol and the reliability of normal colorimetric analysis in detecting iron absorbed from this complex have not been established. We measured increases in serum iron levels in 12 volunteers following oral challenge with four different pharmaceutical formulations of ferric trimaltol in a double-blind, cross-over, randomized study. The conventional colorimetric method for detecting serum iron was compared with thermal analyses after trichloroacetic acid (TCA) treatment of serum. Measurements of serum iron levels by TCA treatment and thermal analysis closely agreed with measurements by colorimetry. For all formulations, serum iron levels peaked at 90 min with a plateau of at least 5 h [mean (standard deviation) peak absorption 8.3% (6.3%) of ingested dose, n=48]. Absorption of iron, based on peak serum values or area under the serum curve, was not different for the four formulations (n=12 each) and correlated with the individual's iron status, as assessed by serum ferritin values (r = -0.6; P < 0.001). Normal colorimetry is suitable for analysis of serum iron levels following ingestion of ferric trimaltol. There is rapid and sustained absorption of iron from ferric trimaltol and, as with ferrous iron, uptake appears to be controlled through normal mechanisms of iron acquisition that depend upon body iron stores.

Oligomeric but not monomeric silica prevents aluminum absorption in humans.

BACKGROUND: Soluble silica, a ubiquitous component of the diet, may be the natural ligand for dietary aluminum and may prevent its accumulation and toxicity in animals. However, previous studies on the inhibition of aluminum absorption and toxicity by soluble silica have produced conflicting results. We recently identified a soluble silica polymer, oligomeric silica, that has a much higher affinity for aluminum than does monomeric silica and that may be involved in the sequestration of aluminum. OBJECTIVE: By using (26)Al as a tracer, we investigated the effects of oligomeric and monomeric silica on the bioavailability of aluminum (study 1) and compared the availability of silicon from oligomeric and monomeric silica in the human gastrointestinal tract (study 2). DESIGN: In study 1, three healthy volunteers each ingested aluminum alone (control), aluminum with oligomeric silica (17 mg), and aluminum with monomeric silica (17 mg). In study 2, five healthy volunteers ingested both the oligomeric and monomeric forms of silica (34 mg). Serum and urine samples were analyzed for aluminum and silicon. RESULTS: Oligomeric silica reduced the availability of aluminum by 67% (P = 0.01) compared with the control, whereas monomeric silica had no effect (P = 0.40). Monomeric silica was readily taken up from the gastrointestinal tract and then excreted in urine (53%), whereas oligomeric silica was not detectably absorbed or excreted. CONCLUSIONS: The oligomeric, high-aluminum-affinity form of soluble silica reduces aluminum availability from the human gastrointestinal tract. Its potential role in the amelioration of aluminum toxicity in other biological systems requires attention.

Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion.

Silicon (Si), as silicic acid, is suggested to be the natural antidote to aluminium (Al) toxicity, and was recently shown to promote the urinary excretion of Al from body stores. The metabolism of Si in man, however, remains poorly investigated. Here we report on the pharmacokinetics and metabolism of Si in healthy volunteers following ingestion of orthosilicic acid (27-55 mg/l Si) in water. We also investigated whether orthosilicic acid promotes the urinary excretion of endogenous Al. Minimum, median uptake of Si from the ingested dose was 50.3% (range: 21.9-74.7%, n = 8) based on urinary analysis following dosing. Significant correlations were observed between creatinine clearance and Si levels in serum or urine (r = 0.95 and 0.99, respectively). Renal clearance of Si was 82-96 ml/min suggesting high renal filterability. These results suggest that orthosilicic acid is readily absorbed from the gastrointestinal tract of man and then readily excreted in urine. There was no significant increase in Al excretion, over 32 h, following ingestion of the orthosilicic acid dose (P = 0.5; n = 5).

Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron.

BACKGROUND: Oral iron supplements, which are usually in the form of ferrous (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe3+) form. AIM: To test whether ferric trimaltol could correct iron deficiency anaemia in patients intolerant of ferrous sulphate. METHODS: Twenty-three patients were recruited from gastroenterology clinics, of whom 1 5 had inflammatory bowel disease, a group often difficult to treat with oral iron. Patients with iron deficiency anaemia and documented intolerance to ferrous sulphate were given 3 months of treatment with ferric trimaltol. RESULTS: Nineteen of 23 patients completed the treatment and anaemia was fully corrected in 14 of these, mean haemoglobin increased from 106 +/- 15 to 126 +/- 16 g/L, and there was a particularly low incidence of side-effects. Of 11 patients with inflammatory bowel disease who completed the study, nine fully corrected their anaemia. CONCLUSION: The results demonstrate that in patients intolerant of ferrous compounds, ferric trimaltol corrects iron deficiency and has a low incidence of side-effects.