Effect of dietary 25-hydroxycholecalciferol on the sternal mass of meat ducks under different vitamin regimens.

Genetic selection and intensive nutrition for increased growth rate in meat-type ducks has resulted in an imbalance between pectorales increment and sternal mass, which is detrimental to productivity and welfare. Reducing body weight and increasing sternal mass probably reverses these adverse effects. Therefore, 2 experiments (Expt.) were conducted to investigate the effects of 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolites, on sternal mass. In Expt. 1, 512 1-day-old male ducks were randomly assigned to 4 low-nutrient density diets and received following treatments in a 2 × 2 factorial arrangement: (i) NRC or China Agricultural industry standards (NY/T) vitamin premixes and (ii) 0.069 mg/kg 25-HyD in feed or not. At 49 D of age, regardless of 25-OH-D3, NY/T vitamin regimen inhibited bone turnover and consequently increased sternal trabecular bone volume and mineral deposition compared with NRC vitamin premix. Supplementing 25-OH-D3 to NRC but not NY/T vitamin regimen significantly improved sternal microarchitecture and mineral content, which companied by decreased serum bone resorption markers concentration, as well as downregulation of the gene expressions of osteoclast differentiation and activity. In Expt. 2, 256 1-day-old male ducks were fed a standard nutrient density diet contained NRC vitamin premix with 0 or 0.069 mg/kg of 25-OH-D3. Results also showed that 25-OH-D3 treatment significantly improved sternal mineral accumulation and microarchitecture, along with decreasing osteoblast and osteoclast numbers in bone surface, declining serum bone turnover markers levels, and increasing serum Ca concentration. Collectively, these findings indicated that the dietary administration of 25-OH-D3 increased sternal mass in NRC vitamin diet by suppressing bone resorption in 49-day-old meat duck.

In-situ forming chitosan implant-loaded with raloxifene hydrochloride and bioactive glass nanoparticles for treatment of bone injuries: Formulation and biological evaluation in animal model.

In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.

Biovalorization of soybean residue (okara) via fermentation with Ganoderma lucidum and Lentinus edodes to attain products with high anti-osteoporotic effects.

Okara, despite being a soybean processing by-product, still holds many nutrients. Thus, considerable attention has been recently paid to its reuse. In this study, solid-state fermentation was performed using Ganoderma lucidum and Lentinus edodes. Antioxidant activity and bioactive compound levels in G. lucidum-fermented okara (GLFO) and L. edodes-fermented okara (LEFO) were assayed. Antiosteoporosis bioactivity was evaluated using an animal model. The results demonstrated that solid-state fermentation significantly improved the antioxidant activity and bioactive compound levels. Furthermore, GLFO and LEFO increased trabecular bone volume, although only the GLFO-treated group exhibited significantly improved trabecular separation compared with the bilateral ovariectomy-treated control group. GLFO-related outcomes were superior to those of LEFO. The results demonstrate that okara products are effective for treating postmenopausal osteoporosis in humans.

Downregulating PI3K/Akt/NF-κB signaling with allicin for ameliorating the progression of osteoarthritis: in vitro and vivo studies.

Osteoarthritis (OA) is characterized by the degeneration and destruction of articular cartilage. Allicin, a dietary garlic active constituent, exerts anti-inflammatory effects on several diseases. However, its effects on OA have not been clearly elucidated. In this study, we explored the effects of allicin on OA in both in vitro and in vivo models. Allicin inhibited interleukin-1ß (IL-1ß) induced overproduction of nitric oxide, inducible nitric oxide synthase, prostaglandin E2, and cyclooxygenase-2, as well as pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in chondrocytes in a dose-dependent manner. Meanwhile, allicin reversed the overproduction of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 and the decrease of aggrecan and type II collagen. Furthermore, allicin dramatically suppressed IL-1ß-stimulated PI3K/Akt/NF-κB activation in chondrocytes. In vivo, treatment with allicin prevented the destruction of cartilage and inhibited PI3K/Akt/NF-κB activation in the cartilage of mice OA models. Taken together, these results indicate that allicin may be a potential therapeutic agent for OA.

Is Vitamin D3 Transdermal Formulation Feasible? An Ex Vivo Skin Retention and Permeation.

Vitamin D3 supplementation is important to prevent and treat hypovitaminosis that is a worldwide public health issue. Most types of supplementation are by oral route or fortification foods. The alternative route must be investigated, as transdermal route, for people with fat malabsorption or other diseases that impair the absorption of vitamin D3. This study focused on verifying the feasibleness of vitamin D3 skin retention and permeation with the presence of chemical penetration enhancers (soybean lecithin, isopropyl palmitate, propylene glycol, ethoxydiglycol, and cereal alcohol) at different pharmaceutical forms (gel and cream) through a human skin. The integrity of skin was evaluated by transepidermal water loss (TEWL) during the skin retention and permeation test. The combination of chemical penetration enhancers presented in cream did not compromise the skin, different from the gel that association of cereal alcohol and propylene glycol compromised the skin in 24 h. Gel formulation showed vitamin D3 detection at stratum corneum in 4 h and at epidermis and dermis in 24 h. Vitamin D3 demonstrated an affinity with the vehicle in the cream formulation and was detected at the skin surface. No active was found at receptor fluid for both formulations. In conclusion, the vitamin D3 did not indicate feasibleness for transdermal use probably due to its physical-chemical characteristics such as high lipophilicity since it was not permeated through a human skin. Nevertheless, the transdermal route should be continuously investigated with less lipophilic derivates of vitamin D3 and with different combination of penetration enhancers.

Effect of buffalo casein-derived novel bioactive peptides on osteoblast differentiation.

PURPOSE: Epidemiological and intervention studies show that milk consumption in childhood and during adolescence is related to higher bone mineral density. Milk and milk products prevent the bone loss in pre- and postmenopausal women. Apart from calcium, there are other biologically active compounds in milk such as bioactive peptides which may play a role in promoting bone health. Casein is the major protein in milk which has also been reported to have numerous biological active peptides within it. The hypothesis of the present study was to identify the key peptides behind osteoanabolic nature of the milk protein, which further can be used to prepare functional foods to alleviate bone diseases like osteoporosis. Hence, this study was carried out to investigate osteogenic nature of four novel bioactive peptides [PEP1 (EDVPSER), PEP2 (NAVPITPTL), PEP3 (VLPVPQK) and PEP4 (HPHPHLSF)] derived from buffalo casein by in vitro osteoblast differentiation model. METHODS: Calvaria cells were isolated from 3-day-old rat pups, cultured under in vitro conditions till confluence and further used for experiments. Calvarial osteoblast cells were cultured in the presence or absence of peptides including positive controls up to 21 days. Effect of peptides was checked at regular intervals by quantifying osteoblast differentiation marker genes (ALP, OCN and COL-1) expression, alkaline phosphatase activity, osteocalcin level in culture supernatants, mineral deposition by alizarin red staining and caspase-3 and 9 assays. RESULTS: The osteoblast differentiation marker genes (ALP, OCN and COL-1) expression was significantly [(p < 0.01) (p < 0.001)] up-regulated in the presence of these peptides. The peptides also significantly induced alkaline phosphatase activity, osteocalcin level and mineral deposition in comparison with the control. It was also observed that all the four peptides did not show any cytotoxic effect during 21-day treatment period. CONCLUSION: All peptides enhanced osteoblast differentiation along with the positive controls. These results hold an immense scope to use peptides as preventive measure for reducing incidence of osteoporosis. These peptides can also be used as drugs and can be utilized as functional ingredients in functional foods preparation for osteoporosis therapy, but in vivo studies are required for further confirmation.

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis.

Milk Basic Protein Facilitates Increased Bone Mass in Growing Mice.

Milk basic protein (MBP) comprises a group of basic whey proteins and is effective in preventing bone loss by promoting bone deposition (bone formation) and suppressing withdrawn (bone resorption). We previously revealed the bone protective effects of MBP during life phases involving excessive bone resorption, such as in adults and postmenopausal women, and in animal models (ovariectomized rats and mice). However, it was unclear whether MBP increases bone mass during the growth stage, when there is more bone formation than resorption. We therefore investigated the effect of MBP supplementation on bone mass in 6-wk-old mice provided water supplemented with MBP [0.01%, 0.1%, 1.0% (w/w)] or deionized water (control) ad libitum for 10 wk. Analysis by micro-computerized tomography showed that MBP significantly increased tibia cortical bone mineral density and femur trabecular bone volume to tissue volume compared with mice provided deionized water. Next, the function of MBP in bone remodeling (bone formation and resorption) was evaluated using an in vitro system and the results demonstrated that MBP directly promoted osteoblast proliferation and inhibited osteoclastogenesis. Moreover, the plasma level of insulin-like growth factor-1 was increased by MBP supplementation, suggesting that MBP indirectly promoted osteoblast proliferation/differentiation. These effects enhance bone formation and/or inhibit bone resorption, resulting in increased bone mass in growing mice.

A Novel H2S-releasing Amino-Bisphosphonate which combines bone anti-catabolic and anabolic functions.

Bisphosphonates (BPs) are the first-line treatment of bone loss resulting from various pathological conditions. Due to their high affinity to bone they have been used to develop conjugates with pro-anabolic or anti-catabolic drugs. We recently demontrated that hydrogen sulfide (H2S), promotes osteogenesis and inhibits osteoclast differentiation. Here we developed an innovative molecule, named DM-22, obtained from the combination of alendronate (AL) and the H2S-releasing moiety aryl-isothiocyanate. DM-22 and AL were assayed in vitro in the concentration range 1-33 µM for effects on viability and function of human osteoclasts (h-OCs) and mesenchymal stromal cells (h-MSCs) undergoing osteogenic differentiation. Amperometric measures revealed that DM-22 releases H2S at a slow rate with a thiol-dependent mechanism. DM-22 significantly inhibited h-OCs differentiation and function, maintaining a residual h-OCs viability even at the high dose of 33 µM. Contrary to AL, in h-MSCs DM-22 did not induce cytotoxicity as revealed by LDH assay, significantly stimulated mineralization as measured by Alizarin Red staining and increased mRNA expression of Collagen I as compared to control cultures. In conclusion, DM-22 is a new BP which inhibits h-OCs function and stimulate osteogenic differentiation of h-MSCs, without cytotoxicity. DM-22 is an ideal candidate for a novel family of osteoanabolic drugs.

[Vitamin D metabolism of the bone]. / Vitamin-D-Stoffwechsel des Knochens.

BACKGROUND: Bone health is a crucial requirement for individual mobility. Preventive, diagnostic, and therapeutic actions to preserve or restore bone health are major tasks for orthopedic surgeons and health practitioners in musculoskeletal medicine. RESULTS: In the context of the widespread vitamin D deficiency in Germany, it is relevant to keep in mind thatserum calcitriol levels above > 30 µg/l are necessary for optimal bone metabolism and bone health. In particular, because vitamin D deficiency not only increases the amount of non-mineralized bone matrix (osteoid), but it can also cause negative changes in the mineralized bone tissue. Widening of the osteons and osteocyte lacunae, together with increased bone aging under the osteoid layer, can lead to reduced fracture resistance. CONCLUSION: Integration of bone metabolism into the orthopedic strategy is an important concept for optimizing treatment in modern musculoskeletal medicine.

Mechanism of enhanced antiosteoporosis effect of circinal-icaritin by self-assembled nanomicelles in vivo with suet oil and sodium deoxycholate.

BACKGROUND: Circinal-icaritin (CIT), one new active aglycone of Epimedium, can exert a beneficial effect on osteoporotic bone. However, its low bioavailability limits its clinical efficacy for the treatment of osteoporosis. MATERIALS AND METHODS: In this paper, suet oil (SO) was used to improve the oral bioavailability of CIT and enhance its antiosteoporosis effect and absorption. After oral administration of CIT together with SO, the CIT and SO self-assembled into nanomicelles under the action of sodium deoxycholate (DOC) by bile secretion. The antiosteoporosis effects of the CIT-SO-DOC nanomicelles were evaluated in osteoporotic rats by bone mineral density, serum biochemical markers, bone microarchitecture, bone biomechanical properties, and related protein and gene expressions. We examined the bioavailability of CIT and its nanomicelles in vivo, and subsequently the nanomicelles were verified using transmission electron microscopy. Finally, we evaluated absorption across a rat intestinal perfusion model. RESULTS: Compared with CIT, in the CIT-SO groups, protein and messenger ribonucleic acid expressions of osteoprotegerin were increased, while expressions of receptor activator of nuclear factor-κB ligand in bone tissue were decreased; bone-turnover markers in serum of hydroxyproline, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, and receptor activator of nuclear factor-κB ligand levels were decreased, while osteoprotegerin and osteocalcin levels were increased; and trabecular bone mass, microarchitecture, and bone biomechanical strength were enhanced. The relative bioavailabilities of CIT-SO high dosage, CIT-SO medium dosage, and CIT-SO low dosage (area under concentration-time curve [AUC]0-∞) compared with that of raw CIT high dosage, CIT medium dosage, and CIT low dosage (AUC0-∞) were 127%, 121%, and 134%, respectively. The average particle size of CIT-DOC was significantly decreased after adding SO (P<0.01), and the intestinal permeability coefficients of CIT-SO-DOC nanomicelles in the duodenum, jejunum, ileum, and colon were all significantly improved (P<0.01). CONCLUSION: The increased antiosteoporosis effects and bioavailability of CIT-SO-DOC self-assembled nanomicelles were due to an increase in absorption of CIT by reducing the particle sizes of CIT. SO may be a practical oral carrier for antiosteoporosis drugs with low bioavailability.

Fabrication and characterization of the nano-composite of whey protein hydrolysate chelated with calcium.

The nano-composites of whey protein hydrolysate (WPH) chelated with calcium were fabricated in aqueous solution at 30 °C for 20 min, with the ratio of hydrolysate to calcium 15 : 1 (w/w). UV scanning spectroscopy, fluorescent spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering and atomic force microscopy were applied to characterize the structure of the WPH-calcium chelate. The nano-composites showed the successful incorporation of calcium into the WPH, indicating the interaction between calcium and WPH. The chelation of calcium ions to WPH caused molecular folding and aggregation which led to the formation of a WPH-calcium chelate of nanoparticle size, and the principal sites of calcium-binding corresponded to the carboxyl groups and carbonyl groups of WPH. The WPH-calcium chelate demonstrated excellent stability and absorbability under both acidic and basic conditions, which was beneficial for calcium absorption in the gastrointestinal tract of the human body. Moreover, the calcium absorption of the WPH-calcium chelate on Caco-2 cells was significantly higher than those of calcium gluconate and CaCl2 in vitro, suggesting the possible increase in calcium bioavailability. The findings suggest that the WPH-calcium chelate has the potential in making dietary supplements for improving bone health of the human body.

Black rice (Oryza sativa L.) extracts induce osteoblast differentiation and protect against bone loss in ovariectomized rats.

Osteoporosis, an age associated skeletal disease, exhibits increased adipogenesis at the expense of osteogenesis from common osteoporotic bone marrow cells. In this study, black rice (Oryza sativa L.) extracts (BRE) were identified as osteogenic inducers. BRE stimulated the alkaline phosphatase (ALP) activity in both C3H10T1/2 and primary bone marrow cells. Similarly, BRE increased mRNA expression of ALP and osterix. Oral administration of BRE in OVX rats prevented decreases in bone density and strength. By contrast, BRE inhibited adipocyte differentiation of mesenchymal C3H10T1/2 cells and prevented increases in body weight and fat mass in high fat diet fed obese mice, further suggesting the dual effects of BRE on anti-adipogenesis and pro-osteogenesis. UPLC analysis identified cyanidin-3-O-glucoside and peonidin-3-O-glucoside as main anti-adipogenic effectors but not for pro-osteogenic induction. In mechanism studies, BRE selectively stimulated Wnt-driven luciferase activities. BRE treatment also induced Wnt-specific target genes such as Axin2, WISP2, and Cyclin D1. Taken together, these data suggest that BRE is a potentially useful ingredient to protect against age related osteoporosis and diet induced obesity.

Combat sports practice favors bone mineral density among adolescent male athletes.

The aim of this study was to determine the impact of combat sports practice on bone mineral density (BMD) and to analyze the relationship between bone parameters and anthropometric measurements, bone markers, and activity index (AI). In other words, to detect the most important determinant of BMD in the adolescent period among combat sports athletes. Fifty athletes engaged in combat sports, mean age 17.1±0.2 yr, were compared with 30 sedentary subjects who were matched for age, height, and pubertal stage. For all subjects, the whole-body BMD, lumbar spine BMD (L2-L4), and BMD in the pelvis, arms, and legs was measured by dual-energy X-ray absorptiometry, and anthropometric measurements were evaluated. Daily calcium intake, bone resorption, and formation markers were measured. BMD measurements were greater in the combat sports athletes than in the sedentary group (p<0.01). Weight, body mass index, and lean body mass were significantly correlated with BMD in different sites. Daily calcium consumption lower than daily calcium intake recommended in both athletes and sedentary group. AI was strongly correlated with all BMD measurements particularly with the whole body, legs, and arms. Negative correlations were observed between bone markers and BMD in different sites. The common major predictor of BMD measurements was AI (p<0.0001). AI associated to lean body mass determined whole-body BMD until 74%. AI explained both BMD in arms and L2-L4 at 25%. AI associated to height can account for 63% of the variance in BMD legs. These observations suggested that the best model predicting BMD in different sites among adolescent combat sports athletes was the AI. Children and adolescents should be encouraged to participate in combat sports to maximize their bone accrual.

Novel, selective vitamin D analog suppresses parathyroid hormone in uremic animals and postmenopausal women.

BACKGROUND: The use of 1α-hydroxylated vitamin D therapy to control secondary hyperparathyroidism in renal failure patients has been a success story, culminating with the demonstration of increased life expectancy in patients treated with these compounds. However, hypercalcemic episodes have been a recurrent problem with these therapies and have resulted in the added use of calcium mimetics. Clearly there is good reason to search for improved vitamin D therapy. In our inventory of vitamin D compounds, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) surfaced as a potential candidate. This was based on its preferential localization in the parathyroid gland and a clear suppression of serum parathyroid hormone (PTH) levels without a change in serum calcium in a clinical trial in postmenopausal women. METHODS: 2MD has now been tested in the rat 5/6-nephrectomy model of renal failure, and in postmenopausal women to determine if it can suppress serum PTH at doses that do not elevate serum calcium and serum phosphorus concentrations. RESULTS: Daily oral treatment of uremic rats on 2.5 ng/bw/day of 2MD dramatically suppressed PTH without a change in serum calcium or serum phosphorus. Further, PTH was suppressed in postmenopausal women after only 3 daily oral doses of 2MD that continued for 4 weeks with no change in serum calcium or serum phosphorus. CONCLUSION: These results coupled with a pharmacokinetic half-life of ~24 h suggest that 2MD given either daily or at the time of dialysis may be a superior therapy for secondary hyperparathyroidism in chronic renal failure patients.

Vitamin D supplementation increases calcium absorption without a threshold effect.

BACKGROUND: The maximal calcium absorption in response to vitamin D has been proposed as a biomarker for vitamin D sufficiency. OBJECTIVE: The objective was to determine whether there is a threshold beyond which increasing doses of vitamin D, or concentrations of serum 25-hydroxyvitamin D [25(OH)D], no longer increase calcium absorption. DESIGN: This was a placebo-controlled, dose-response, randomized, double-blind study of the effect of vitamin D on calcium absorption in healthy postmenopausal women. Seventy-six healthy postmenopausal women were randomly assigned to placebo or 800 IU (20 µg), 2000 IU (50 µg), or 4000 IU (100 µg) vitamin D3 for 8 wk. The technique of dual isotopes of stable calcium was used with a calcium carrier to measure calcium absorption at baseline and after 8 wk. RESULTS: Seventy-one women with a mean ± SD age of 58.8 ± 4.9 y completed the study. The mean calcium intake was 1142 ± 509 mg/d and serum 25(OH)D was 63 ± 14 nmol/L at baseline. A statistically significant linear trend of an increase in calcium absorption adjusted for age and body mass index with increasing vitamin D3 dose or serum 25(OH)D concentration was observed. A 6.7% absolute increase in calcium absorption was found in the highest vitamin D3 group (100 µg). No evidence of nonlinearity was observed in the dose-response curve. CONCLUSIONS: No evidence of a threshold of calcium absorption was found with a serum 25(OH)D range from 40 to 130 nmol/L. Calcium absorption in this range is not a useful biomarker to determine nutritional recommendations for vitamin D.

Biotransformations of prenylated hop flavonoids for drug discovery and production.

In this review we aim to present current knowledge on biotransformation of flavonoids from hop cones with respect to type of product, catalyst and conversion. Subsequently, a comparative analysis of biological activity of prenylated hop flavonoids and their biotransformation products has been performed in order to indicate these research efforts that have good potential for application in pharmaceutical industry. There is increasing evidence that the products of biotransformation of hop prenylflavonoids, which have been little studied until recently, can be used as drugs or drug ingredients and also as standards of human drug metabolites. They can also serve as an inspiration for the design and chemical synthesis of new derivatives with higher or different biological activity. Nevertheless, much additional work, among others on determining the mechanism of action in in vivo systems, is needed to open up the way to biomedical application of these compounds.

Functions and mechanisms of green tea catechins in regulating bone remodeling.

Osteoporosis is caused by an imbalance in bone remodeling, a process involving bone-building osteoblasts and bone-resorptive osteoclasts. Excessive reactive oxygen species and inflammatory responses have been shown to stimulate differentiation and function of osteoclasts while inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation via extracellular signal-regulated kinases (ERK), ERK-dependent nuclear factor-κB and Wnt/ß-catenin signaling pathways. The anti-oxidant and anti-inflammatory green tea catechins (GTC) have been shown to promote osteoblastogenesis, suppress osteoclastogenesis and stimulate the differentiation of mesenchymal stem cells into osteoblasts rather than adipocytes by modulating the signaling pathways. This paper reviews the pharmacokinetics and metabolism of GTC, their bone-protective activities evidenced in in vitro and in vivo studies, and the limited clinical studies supporting these preclinical findings. In light of the physical, economical, and social burdens due to osteoporosis, easily accessible and affordable preventive measures such as GTC deserves further clinical studies prior to its clinical application.

[The role of vitamin D deficiency in the pathogenesis of falls and fractures]. / A D-vitamin-hiány szerepe az elesések és csonttörések patogenezisében.

The diverse effects of vitamin D in human body became known during the last years. Vitamin D deficiency causes many problems in medical care. Important roles of vitamin D are the regulation of calcium metabolism and the effect on bone metabolism. The authors review literature data on vitamin D deficiency recognized as an important risk factor in the pathogenesis of falls and fractures and they call attention of Hungarian physicians to the importance of vitamin D substitution. Supplementation of vitamin D deficiency is particularly important in the elderly age-group.