Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy.
Silicon (Si) is the most abundant element present in the Earth’s crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.
The full text article (link above) has a subsection on osteoporosis:
…Interestingly, the administration of silicon in a controlled clinical study induced a significant increase in femoral bone mineral density in osteoporotic women . Direct relationship between silicon content and bone formation has been shown by Moukarzel et al. . They found a correlation between decreased silicon concentrations in total parenterally fed infants with a decreased bone mineral content. This was the first observation of a possible dietary deficiency of silicon in humans. A randomized controlled animal study on aged ovariectomized rats revealed that long-term preventive treatment with ch-OSA prevented partial femoral bone loss and had a positive effect on the bone turnover . Dietary silicon is associated with postmenopausal bone turnover and bone mineral density at the women’s age when the risk of osteoporosis increases. Moreover, in a cohort study on 3198 middle-aged woman (50–62 years) it was shown that silicon interacts with the oestrogen status on bone mineral density, suggesting that oestrogen status is important for the silicon metabolism in bone health .
Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort.
The role of dietary silicon in bone health in humans is not known. In a cross-sectional, population-based study (2847 participants), associations between dietary silicon intake and BMD were investigated. Dietary silicon correlated positively and significantly with BMD at all hip sites in men and premenopausal women, but not in postmenopausal women, suggesting that increased silicon intake is associated with increased cortical BMD in these populations.
Osteoporosis is a burgeoning health and economic issue. Agents that promote bone formation are widely sought. Animal and cellular data suggest that the orthosilicate anion (i.e., dietary silicon) is involved in bone formation. The intake of silicon (Si, approximately 30 mg/day) is among the highest for trace elements in humans, but its contribution to bone health is not known.
In a cross-sectional, population-based study, we examined the association between silicon intake and bone mineral density (BMD) in 1251 men and 1596 pre- and postmenopausal women in the Framingham Offspring cohort (age, 30-87 years) at four hip sites and lumbar spine, adjusting for all potential confounding factors known to influence BMD and nutrient intake. Silicon intake correlated positively with adjusted BMD at four hip sites in men and premenopausal women, but not in postmenopausal women. No significant association was observed at the lumbar spine in any group. Categorical analysis by Si intake, or energy-adjusted Si intake, supported these findings, and showed large differences in BMD (up to 10%) between the highest (> 40 mg Si/day) and lowest (< 14 mg Si/day) quintiles of silicon intake. A significant association at the lumbar spine in men was also observed. Further analyses indicated that some of the effects seen for moderate consumption of alcoholic beverages on BMD might be attributed to Si intake.
These findings suggest that higher dietary silicon intake in men and younger women may have salutary effects on skeletal health, especially cortical bone health, that has not been previously recognized. Confirmation of these results is being sought in a longitudinal study and by assessment of the influence of silicon intake on bone markers in this cohort.
Jugdaohsingh R, Tucker KL, Qiao N, Cupples LA…
J. Bone Miner. Res. Feb 2004 PMID: 14969400
Silicon deprivation decreases collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver.
We have shown that silicon (Si) deprivation decreases the collagen concentration in bone of 9-wk-old rats. Finding that Si deprivation also affects collagen at different stages in bone development, collagen-forming enzymes, or collagen deposition in other tissues would have implications that Si is important for both wound healing and bone formation. Therefore, 42 rats in experiment 1 and 24 rats in experiment 2 were fed a basal diet containing 2 or 2.6 microg Si/g, respectively, based on ground corn and casein, and supplemented with either 0 or 10 microg Si/g as sodium metasilicate. At 3 wk, the femur was removed from 18 of the 42 rats in experiment 1 for hydroxyproline analysis. A polyvinyl sponge was implanted beneath the skin of the upper back of each of the 24 remaining rats. Sixteen hours before termination and 2 wk after the sponge had been implanted, each rat was given an oral dose of 14C-proline (1.8 microCi/100 g body wt). The total amount of hydroxyproline was significantly lower in the tibia and sponges taken from Si-deficient animals than Si-supplemented rats. The disintegrations per minute of 14C-proline were significantly higher in sponge extracts from Si- deficient rats than Si-supplemented rats. Additional evidence of aberrations in proline metabolism with Si deprivation was that liver ornithine aminotransferase was significantly decreased in Si-deprived animals in experiment 2. Findings of an increased accumulation of 14C-proline and decreased total hydroxyproline in implanted sponges and decreased activity of a key enzyme in proline synthesis (liver ornithine aminotransferase) in Si-deprived animals indicates an aberration in the formation of collagen from proline in sites other than bone that is corrected by Si. This suggests that Si is a nutrient of concern in wound healing as well as bone formation.
Short-term effects of organic silicon on trabecular bone in mature ovariectomized rats.
Silicon is known to ensure an essential role in the formation of cross-links between collagen and proteoglycans during bone growth. In this study, we have evaluated the short-term effects of a preventive treatment with silanol, a soluble organic silicon (Si), on trabecular bone in mature ovariectomized rats. Three-month-old rats were sham-operated (sham) or were ovariectomized (OVX) and treated with 10 micrograms/kg/day of 17 beta estradiol (E2), or with 0.1 mg Si/kg/day or 1.0 mg Si/kg/day of silanol for 1 month. Plasma alkaline phosphatase and osteocalcin levels were increased by 50% in OVX rats compared with sham rats and were corrected by E2 but not by silanol treatment. The trabecular bone volume measured at the tibial metaphysis was decreased by 48%, and histomorphometric indices of bone resorption and formation were increased in OVX rats compared with sham, and these parameters were corrected by E2 treatment. Treatment of OVX rats with silanol decreased the osteoclast surface by 31% and the number of osteoclasts by 20%. The mineral apposition rate, the bone formation rate, and the osteoblast surface at the tibia metaphyseal area were increased by 30% at the higher dose of silanol compared with OVX rats. In contrast, silanol treatment had no effect on the periosteal apposition rate. The reduction of the metaphyseal bone resorption and the increased bone formation induced by silanol resulted in a slight improvement of the trabecular bone volume (+14%) compared with controls.
Hott M, de Pollak C, Modrowski D, Marie PJ
Calcif. Tissue Int. Sep 1993 PMID: 8242469
Silicon: a requirement in bone formation independent of vitamin D1.
Silicon has been reported to be involved in an early stage of bone formation as a result of earlier in vitro and in vivo studies in this laboratory. It is now possible to demonstrate that silicon exerts an effect on bone formation independent of the action of vitamin D. Day-old cockerels were fed Si-deficient and Si-supplemented diets with adequate and no dietary vitamin D under trace element controlled conditions. At the end of 4 weeks chicks receiving dietary vitamin D3 (600 IU) exhibited optimal rates of growth whereas the growth rates of chicks receiving D2 (6000 IU) and no vitamin D were markedly depressed. There were no significant differences between growth of Si-deficient and Si-supplemented chicks on the same level of vitamin D. Skull and bone size was proportional to overall chick growth. However, all chicks on Si-deficient diets irrespective of the level of dietary vitamin D had gross abnormalities of skull architecture, the overall skull appearance being narrower and shorter. The frontal area was narrower and the dorsal median line at the front parietal junction was depressed with a narrowing both posterior and laterally, stunting parietal and occipital areas. These abnormal areas showed fewer trabeculae and less calcification. Analyses of skull frontal bones for hexosamine, collagen, noncollagenous protein, and bone mineral demonstrated that the major difference was in collagen content, the Si-deficient skulls showing considerably less collagen at each level of vitamin D. These findings demonstrate that silicon has a significant effect on the bone matrix independent of vitamin D, and support the earlier postulate that silicon is involved in an early stage of bone formation.
Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial.
Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial.
Over 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 microg cholecalciferol (Vit D3) and three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. Bone formation markers in serum and urinary resorption markers were measured at baseline, and after 6 and 12 months. Femoral and lumbar BMD were measured at baseline and after 12 months by DEXA.
Overall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP) was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo) without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I). Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur < -1) however was significant for the 6 mg dose at the femoral neck (T-test). There were no ch-OSA related adverse events observed and biochemical safety parameters remained within the normal range. Combined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis.
Collagen provides elasticity and structure in all connective tissues and several studies have indicated that collagen is important for bone toughness [43-45] whereas the mineral component is mainly involved in providing stiffness. Wang et al.  demonstrated that the mechanical integrity of collagen fibres deteriorates with ageing in human cortical bones and is associated with a higher fracture risk. When the collagen network becomes weaker with age, it will result in decreased toughness, possibly due to a reduction in natural cross-links or silicon content. It has previously been suggested that Si may be an integral (structural) component of connective tissues as high levels of non-dialysable Si has been reported in connective tissues and their components suggesting strong (covalent) associations .
Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.
Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.
Calomme M, Geusens P, Demeester N, Behets GJ…
Calcif. Tissue Int. Apr 2006 PMID: 16604283
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.
Reffitt DM, Ogston N, Jugdaohsingh R, Cheung HF…
Bone Feb 2003 PMID: 12633784
Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which presently in the UK results in over 200,000 fractures annually at a cost of over one billion pounds. Figures are set to increase worldwide. Understanding the factors which affect bone metabolism is thus of primary importance in order to establish preventative measures or treatments for this condition. Nutrition is an important determinant of bone health, but the effects of the individual nutrients and minerals, other than calcium, is little understood. Accumulating evidence over the last 30 years strongly suggest that dietary silicon is beneficial to bone and connective tissue health and we recently reported strong positive associations between dietary Si intake and bone mineral density in US and UK cohorts. The exact biological role(s) of silicon in bone health is still not clear, although a number of possible mechanisms have been suggested, including the synthesis of collagen and/or its stabilization, and matrix mineralization. This review gives an overview of this naturally occurring dietary element, its metabolism and the evidence of its potential role in bone health.
Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet.
Osteoporosis and low bone mineral density affect millions of Americans. The majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health. In addition, specific nutritional factors may improve calcium metabolism and bone formation. It is the authors’ opinion that nutritional supplements should attempt to provide ample, but not excessive, amounts of factors that are frequently insufficient in the typical American diet. In contrast to dietary insufficiencies, several nutrients that support bone health are readily available in the average American diet. These include zinc, manganese, and copper which may have adverse effects at higher levels of intake. Some multivitamins and bone support products provide additional quantities of nutrients that may be unnecessary or potentially harmful. The purpose of this paper is to identify specific nutritional components of bone health, the effects on bone, the level of availability in the average American diet, and the implications of supplementation for each nutritional component. A summary of recommended dietary supplementation is included.
Oral intake of 2 gm/day of strontium ranelate have improved bone strength and reduced fracture rates in women with osteoporosis, but there are reports of increased risks of venous blood clots and memory loss [82, 87].