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PubMed1976

Acute administration of 25-hydroxycholecalciferol in man.

Serum 25-hydroxyvitamin D responses to oral doses of 25-hydroxycholecalciferol were measured in healthy volunteers. Peak serum 25-hydroxyvitamin D levels occurred 4 to 8 hours after doses of 1.5, 5, and 10 mug per kg of body weight. The mean increments above baseline serum 25-hydroxyvitamin D concentrations at 4 hours were linear over this dose range. Following a single oral dose, serum 25-hydroxyvitamin D levels fell to 33% of their peak values after one week. The serum 25-hydroxyvitamin D responses measured by competitive protein-binding radioassay were similar to the serum 3H responses exhibited by three volunteers who received simultaneous oral doses of 3H 25-hydroxycholecalciferol and 14C-cholecalciferol. The appearance of 14C in plasma was slower and less marked compared with 3H, probably reflecting a more rapid plasma clearance of the 14C-cholecalciferol. The disappearance of 25-hydroxycholecalciferol from the circulation of two volunteers following acute intravenous delivery of 1.0 mg of 25-hydroxycholecalciferol was multiphasic over 10 days. 60% of the dose administered remained in the circulation 24 hours after the dose. When analyzed several days after single 10 mug/kg oral doses of 25-hydroxycholecalciferol to 4 volunteers, the mean rate of decline to total serum 25-hydroxycholecalciferol was slow (t 1/2 = 22 days). When baseline serum 25-hydroxyvitamin D levels were subtracted, however, the apparent serum half-life of administered 25-hydroxycholecalciferol was 12 days, similar to that reported after tracer doses of 3H-25-hydroxycholecalciferol. The rapid and predictable serum 25-hydroxyvitamin D increases following the oral administration of 25-hydroxycholecalciferol suggest its possible therapeutic advantages compared with vitamin D administration.

Administration, Oral↗
PubMed1981

Pharmacology and therapeutic use of vitamin D and its analogues.

The term vitamin D is generally used to describe a number of chemically related compounds with common antirachitic properties, but which have differences in the rapidity of their action, the way they are produced in the body, and the conditions under which their results are optimal. Ergocalciferol, cholecalciferol, 25-hydroxycholecalciferol (calcifediol), dihydrotachysterol, 1 alpha-hydroxycholecalciferol (alfacalcidol), and 1,25-dihydroxycholecalciferol (calcitriol) are currently the most commonly used vitamin D metabolites. In man, cholecalciferol produced on the skin and the fraction obtained from the diet in the gastrointestinal tract are converted in the liver to 25-hydroxycholecalciferol and then in the kidney to 1,25-dihydroxycholecalciferol. The demonstration of these metabolic pathways has helped to elucidate the aetiology of such conditions a hepatobiliary osteodystrophy, drug-induced anticonvulsant osteomalacia, the hypocalcaemia of hypoparathyroidism and above all azotaemic osteodystrophy. In the therapy of azotaemic osteodystrophy, the period of 'vitamin D resistance' when large doses of vitamin D2 and D3 had to be used is now over, and these patients can be efficiently and successfully treated with almost physiological doses of 1 alpha-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. Attention to diet, calcium supplements and oral phosphate binders are also important. During repetitive haemodialysis, the above principles still hold true, but in some of these patients an osteomalacic syndrome resistant to 1,25-dihydroxycholecalciferol has been recognised. These patients readily become hypercalcaemic when given 1,25-dihydroxycholecalciferol and their fractures and osteomalacia do not improve. Aluminium intoxication, possibly related to the use of impure dialysis fluid, is currently thought to be the most likely explanation of this dialysis osteomalacic syndrome.

Bone Diseases↗
PubMed1984

Fate of tritium-labeled vitamin D3 and 25-hydroxyvitamin D3 in rabbit does and their pups.

Mammary transfer of label from intraperitoneally injected 50 microCi [1 alpha, 2 alpha(n)-hydrogen-3] cholecalciferol, and 50 microCi (26,27-methyl-hydrogen-3)cholecalciferol was studied in nursing rabbits. Does were injected at 3 days postpartum with one of the two labeled compounds. Pups were killed at either 1, 2, 3, 4, or 5 days after dosing of the does, and does were killed after 5 days. Concentrations of radioactivity were greater in tissues of does dosed with tritiated vitamin D3 than in tissues of those dosed with tritiated 25-hydroxyvitamin D3. Concentrations of radioactivity were greater in maternal tissues than in tissues of pups. On the 5th day following administration of tritiated vitamin D3 or 25-hydroxyvitamin D3, the major portion of the radioactivity in does plasma and liver was associated with tritiated 25-hydroxyvitamin D3. In pups from the tritiated vitamin D3 group, the concentration of plasma radioactivity associated with 25-hydroxyvitamin D3 (isolated by high pressure liquid chromatography) increased significantly with time, reaching 85% of the total vitamin D and metabolite radioactivity in the pups at the 5th day. Over 90% of the total recovered plasma radioactivity of pups of the tritiated 25-hydroxyvitamin D3 group was associated with the 25-hydroxyvitamin D3. Much more radioactivity was secreted in the milk of tritiated 25-hydroxyvitamin D3 dosed does than in milk of does dosed with tritiated vitamin D3.

Animals↗
PubMed1975

Binding of 7-dehydrocholesterol to sterol carrier protein and vitamin D3 effect.

It was confirmed that delta 5,7-sterol delta 7-reductase activity was suppressed by cholecalciferol (vitamin D3) in the enzyme system consisted of microsomes and sterol carrier protein (SCP). The enzyme activity was significantly decreased in the combination with microsomes obtained from either vitamin D-deficient or vitamin D3-treated rat liver and with SCP obtained from vitamin D3-treated rat. It was also demonstrated by the binding assay of the dextran-charcoal technique that 7-dehydrocholesterol binding to SCP could be specifically displaced by vitamin D3. The inhibition of cholecalciferol on 7-dehydrocholesterol binding to liver SCP was confirmed to be non-competitive inhibition.

Animals↗
PubMed2002

[Increased serum levels of vitamin D and calcium in young men after replacement of butter with soft margarine in usual diet].

Osteoporosis features include reduction of bone mass and increased predisposition to fractures. Osteoporosis is considered as one of frequent diseases developing in menopausal women and old men. The values of peak bone mass are the determinant of osteoporosis development. It is estimated that the peak bone mass is reached at the age between 16 and 30 years. (NIH Consensus, 2001). Insufficient intake of calcium and vitamin D in diet, with reduced sun exposure, low physical activity, low body weight are well documented risk factors for this disease in human. For that reason, in osteoporosis prevention it should be tried to ensure adequate supply of calcium in diet from early life, with adequate supply of vitamin D, as factors determining adequate mineralization of osseous tissue. The study was carried out for assessing changes of the levels of calcium and 25-OH cholecalciferol in serum replacing butter in usual diet with margarine enriched with vitamin D. After a period of diet stabilization the study group received first diet with butter, followed by diet with margarine in place of butter. Throughout the whole experiment the diet contained unchanged amounts of dairy products as a source of alimentary calcium. In the experiment 41 young healthy men aged 22.6 +/- 1.2 years participated. Every subject consumed in a period of 4 weeks 30 g of butter daily, and during the following 4 weeks margarine 30 g daily. Substitution of margarine for butter in usual diet raised 25-OH cholecalciferol level in serum by 5.56 ng/ml, that is 32.4% (p < 0.001), with consequent 0.12 mg (5%) rise of serum calcium level (p < 0.05). The intake of calcium with diet from dairy products was unchanged throughout the experiment 576-581 mg daily, that is 72% of the recommended intake. The obtained results suggest that independently of the amount of vitamin D intake with food and calcium with diet substitution of margarine enriched with vitamin D for butter was beneficial raising serum vitamin D level, and at the same time increasing calcium absorption from food. It can be accepted that the obtained results could support the opinion on beneficial effects of the consumption of high-quality margarine in daily diet as prevention of the development not only of atherosclerosis but also osteoporosis.

Adult↗
PubMed2003

Kidney function and age related mineral imbalance in postmenopausal women with osteopenia/osteoporosis.

BACKGROUND: Negative mineral balance in postmenopausal women appears to be an important risk factor for osteoporosis and subsequent bone fractures. Its pathogenesis has not been elucidated. OBJECTIVES: To elucidate the participation of the kidney and ageing on mineral balance in postmenopausal women. METHODS: 36 postmenopausal women with osteopenia or osteoporosis, aged 46-75 years were evaluated by determination of mineral balance, kidney functions, 25(OH)-cholecalciferol [25(OH)D], 1,25(OH)2-cholecalciferol [1,25(OH)2D] and intact parathormone plasma levels. RESULTS: Plasma calcium (Ca) concentrations were low and they did not decrease further with ageing. Urinary Ca excretion decreased (r = -0.425, p < 0.01) with age without changes in the fractional excretion of Ca. A similar decrease of urinary excretion was found in the urinary excretion of phosphorus (Pi) (r = -0.335; p < 0.03) and magnesium (Mg) (r = -0.355; p < 0.03). All patients' kidney functions were in the age-related reference range. Plasma 25(OH)D concentrations were in the range of moderate to severe deficiency, related inversely to age (r = -0.357; p < 0.03) and Ca urinary excretion (r = 0.343; p < 0.04) and to plasma creatinine concentration (r = 0.381; p < 0.02). Plasma 1,25(OH)2D concentrations were also low, they did not change with age and were highly correlated with Ca urinary excretion (r = 0.458; p < 0.005). The intact parathormone (iPTH) plasma concentrations were in the reference range, without any changes during aging. CONCLUSIONS: Pi, Mg and dominantly Ca imbalance in postmenopausal women with osteopenia or osteoporosis accentuates with age and besides their insufficient intake the vitamin D deficiency takes part. These data support the need for increased supplementation of Ca and vitamin D with increasing age. (Tab. 3, Fig. 4, Ref. 18.).

Aged↗
PubMedDate not supplied

[Kinetics and action mechanism of vitamin D3 in the process of lipid and blood plasma oxidation in model system].

Kinetics and mechanism of vitamin D3 action were investigated in the process of initiated oxidation of various modeling systems in comparison with activity of various antioxidants such as: alpha-tocopherol, dibunol, alpha-tocopheryl quinone, ubiquinone Q10, philloquinone and beta-carotene. Vitamin D3 addition increased initial and maximal rates of oxygen consumption. The length of circuits, value of a kinetic parameter k2/square root k6, describing oxidability of system as a whole was also increased. Cholecalciferol concentrations exceeding 7.5 x 10(-6) M inhibited these processes. Increase of conjugated dienes was proportional to vitamin D3 concentration. Vitamin D3 did not influence kinetics of accumulation of TBA-reactive products. These results may be explained by high lability of cholecalciferol, which may represent an additional source of free radicals.

Antioxidants↗
PubMed1975

Structural requirements for the interaction of 1 alpha, 25-(OH) 2- vitiamin D3 with its chick interestinal receptor system.

The mechanism by which 1 alpha,25-dihydroxycholecalciferol (1alpha,25-(OH)2D3), the biologically active metabolite of cholecalciferol (vitamin D3), stimulates intestinal calcium absorption has been shown to involve an interaction of the steroid with a specific cytosol-chromatin receptor system in this target organ. Thus, 1alpha,12(OH)2D3 binds to a specific cytoplasmic receptor protein and then, following a temperature-dependent step, becomes associated with a finite number of chromatin acceptor sites prior to the initiation of the physiological response. In this respect, 1alpha,25(OH) 2D3 is similar to a number of other steroid hormones. In this investigation, studies were performed to help define the essential structural features required for interaction of 1alpha,25-(OH)2D3 with its intestinal receptor system, and presumably, for biological activity. To this end, competition studies utilizing a series of closely related structural analogs of cholecalciferol were carried out by means of a competitive binding assay highly specific for 1alpha,25(OH)2D3. The competitive binding assay employed in this study is dependent upon the ability to duplicate, in vitro, the conditions which permit the saturable binding of 1alpha,25-(OH)2[3H]D3 to chick intestinal chromatin, in vivo. Optimal conditions for this assay were achieved by the incubation of a reconstituted intestinal receptor system consisting of separately isolated cytosol and Triton X-100 chromatin fractions at 25 degrees for 45 min with 2.0 X 10-8 M 1alpha,25-(OH)2[3H]D3. Maximal binding of about 21 to 24 pmol of radioactive steroid bound per chick intestinal chromatin occurred under these conditions. The ability of the various analogs to compete with the radioactive hormone was assessed by virtue of a decrease in the amount of radioactive steroid bound to the chromatin in the presence of increasing concentrations of nonradioactive analog.

Animals↗
PubMed1989

Effect of vitamin D3 derivatives on cholesterol synthesis and HMG-CoA reductase activity in cultured cells.

Treatment of logarithmically growing rat intestinal epithelial cells (IEC-6) in culture with vitamin D3 (cholecalciferol), 25-hydroxy vitamin D3 (25-hydroxy cholecalciferol), 1,25-dihydroxy vitamin D3 (1,25-dihydroxycholecalciferol), and 24,25 dihydroxy vitamin D3 (24(R),25-dihydroxycholecalciferol), caused an inhibition of the cholesterol biosynthetic pathway at two separate sites. At concentrations greater than 2 micrograms/ml, the hydroxylated forms of vitamin D3 caused an accumulation of methyl sterols indicating an inhibition of lanosterol demethylation. Vitamin D3, however, had little effect on lanosterol demethylation. A second site of inhibition occurs at 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis at concentrations less than 2 micrograms/ml. All vitamin D3 compounds, except 1,25-dihydroxy vitamin D3, inhibited HMG-CoA reductase activity in a concentration-dependent manner. The lack of inhibition of HMG-CoA reductase activity by 1,25-dihydroxy vitamin D3 in IEC-6 cells was not due to impaired uptake, since 1,25-dihydroxy vitamin D3 caused an accumulation of methyl sterols under similar conditions. The inhibition of HMG-CoA reductase activity and cholesterol synthesis by vitamin D3 and 25-hydroxy vitamin D3 was also observed in other cell culture lines such as human skin fibroblasts (GM-43), transformed human liver cells (Hep G2), and mouse peritoneal macrophages (J-774). On the other hand, 1,25-hydroxy vitamin D3 showed effects on HMG-CoA reductase activity that varied with the cell line. In J-774 and human skin fibroblasts, 1,25-dihydroxy vitamin D3 showed a biphasic effect on reductase activity such that at low concentrations reductase activity was inhibited but was restored to control values at high concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Toxicity of a vitamin D3 rodenticide to dogs.

As a follow-up to an investigation of 2 dogs that died as a result of apparent toxicosis attributable to a cholecalciferol-containing rodenticide, we tested the toxicity of this product in dogs. Two groups of 2 dogs each were fed amounts of rodenticide that provided 20 and 10 mg of cholecalciferol/kg of body weight (approx one fourth and one eighth of the published LD50, respectively). All dogs developed hypercalcemia and hyperphosphatemia and then died. Major lesions were gastrointestinal hemorrhage, myocardial necrosis, and mineralization of vascular walls. Our data indicate that cholecalciferol-containing rodenticides pose a much greater hazard to dogs than was previously believed.

Animals↗
PubMed1986

Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.

Previous studies have shown that recombinant interferon gamma (IFN-gamma), crude T cell supernatants, or appropriate T-cell lines can cause total inhibition of the growth of M. tuberculosis inside murine peritoneal macrophages. In similar experiments with human monocytes much smaller effects are seen. This could be due to the relative immaturity of these cells. Because dihydroxy vitamin D3 (1,25-(OH)2 D3) can cause phenotypic differentiation of immature leukemic lines into macrophage-like cells, we have explored the possibility that exposure to cholecalciferol metabolites in vitro might increase the ability of monocytes to control proliferation of M. tuberculosis, or cause monocytes to mature into cells able to respond appropriately to IFN-gamma. Incubation of monocytes with three cholecalciferol metabolites induced anti-tuberculosis activity to an extent that correlated with their binding affinities to the intracellular receptor protein for the derivatives. 1,25-(OH)2 D3 also primed monocytes for phorbol myristate acetate-triggered reduction of nitroblue tetrazolium. The effects were additive rather than synergistic with those of IFN-gamma. Monocytes incubated with IFN-gamma developed 25-OH D3 1-hydroxylase activity, detected by conversion of tritiated 25-(OH) D3 to a more polar metabolite which coeluted with 1,25-(OH)2 D3 on straight and reverse-phase HPLC. The latter is a more active form in vivo. These findings help to explain claims for the efficacy of vitamin D in the treatment of some forms of tuberculosis, and also the occasional finding of raised serum calcium, and disturbed vitamin D metabolism in these patients.

Cells, Cultured↗
PubMed1982

Intestinal loss of vitamin D3 metabolites in rats with cirrhosis of the liver.

The metabolism of cholecalciferol (vitamin D3) was studied in cirrhotic and in control rats that were either depleted of or supplemented with vitamin D3. The vitamin was supplemented by s.c. injections of radiolabeled cholecalciferol at doses which meat the daily nutritional requirements of rats. Excretion of vitamin D3 metabolites in the feces of the cirrhotic rats was greater than that in the control rats. Fecal excretion consisted mainly of vitamin D3 ester the unchanged vitamin D3 and 25-hydroxyvitamin D3. It is suggested that one of the causes for vitamin D3 depletion in cirrhosis of the liver is fecal loss.

Animals↗
PubMed1983

Acute vitamin D3 toxicosis in horses: case reports and experimental studies of the comparative toxicity of vitamins D2 and D3.

Acute vitamin D toxicosis was diagnosed in 2 horses fed a grain ration containing 1,102,311 IU of cholecalciferol (vitamin D3)/kg (500,000 IU/lb) for about 30 days. Horse 1 died acutely with extensive mineralization of cardiovascular and other soft tissues. Horse 2, which had severe clinical signs and clinicopathologic changes of toxicosis, was treated with nonsteroidal antiinflammatory drugs and recovered in about 6 months. In an experimental study, the toxicity of ergocalciferol (vitamin D2) and cholecalciferol was compared in 2 horses (No. 3 and 4) given the respective vitamins at a daily dosage of 33,000 IU/kg of initial (day 0) body weight for 30 days. Except for slight loss in body weight (8%) during the 1st few days of treatment, horse 3 remained clinically normal. Horse 4 developed limb stiffness and tachycardia, became anorectic, weak, and recumbent, lost 29% of body weight, and had polydipsia and polyuria. Horses 2, 3, and 4 developed persistent hyperphosphatemia. Horse 2 remained normocalcemic whereas horses 3 and 4 became hypercalcemic by day 28. In horse 3, serum vitamin D2 metabolite concentrations on days 0, 1, 14, and 26 were: vitamin D2 (ng/ml) = less than 5.0, 5.7, 71.4, and 188.0; 25-hydroxy-vitamin D2 (ng/ml) = less than 5.0, less than 5.0, 43.1, and 117.5; and 1,25-dihydroxy-vitamin D (pg/ml) = 19.7, 23.2, 25.0, and 45.7, respectively. In horse 4, serum vitamin D3 metabolite concentrations on the same days were: vitamin D3 (ng/ml) = less than 5.0, 110.0, 1,049.0, and 887.0; 25-hydroxy-vitamin D3 (ng/ml) = less than 5.0, 18.9, 201.0 and 182.0; and 1,25-dihydroxy-vitamin D (pg/ml) = 21.5, 18.9, 25.2, and 21.6, respectively. Urine of horses 2 and 4 became acidic (pH 6). Horses 2, 3, and 4 became hyposthenuric, but the decrease in urine specific gravity (sp gr) in horse 3 occurred only after 3 weeks of treatment and was only moderate (sp gr, 1.018 to 1.021) and nonprogressive. Hyposthenuria was evident in horse 4 on day 4 (sp gr, 1.028), and was progressive and marked (sp gr, days 28 to 32: 1.006 to 1.009). Urine sp gr of horse 2 ranged from 1.002 to 1.007. Fractures were demonstrated radiographically and histologically in the costochondral junctions of horses 3 and 4. Mineralization of cardiovascular and other soft tissues developed in horses 3 and 4, with lesions being more severe and having a wider tissue distribution in horse 4.

Acute Disease↗
PubMedDate not supplied

[Vitamin D3 transport across the intestines and its metabolism in the liver of rats with alloxan diabetes].

Vitamin D3 intestinal transport and liver metabolism were studied in rats with alloxan-induced diabetes. The condition was induced by i.v. alloxan injection in a dose of 40 mg/kg b.m. Diabetes development was monitored by blood serum glucose measurements, carried out for 30 days. [3H]-cholecalciferol absorption in the rat intestine was found inhibited in the diabetic animals as against the reference animals, which fact results in disordered entry of vitamin D3 to the body. [3H]-cholecalciferol absorption by the liver is reduced in the examined condition, and the time of its metabolism is increased more than threefold as against the reference animals. The share of vitamin D3 hydroxylation by the liver of diabetic rats is also significantly reduced. The described disorders are responsible, among other things, for the reduction of the levels of vitamin D3 active metabolites in the blood serum of rats with experimental diabetes.

Animals↗
PubMed1997

Effects of vitamin D3 and ecdysterone on free-radical lipid peroxidation.

Free-radical-induced lipid peroxidation was studied in vivo by measuring chemiluminescence of tissues from vitamin D-deficit animals before and after peroral administration of low-molecular-weight biological steroids vitamin D3 (cholecalciferol) and ecdysterone. The kinetics of lipid chemiluminescence in model systems in vitro were determined in blood serum and microsomal and mitochondrial fractions of the liver. Vitamin D3 (cholecalciferol) and ecdysterone displayed antiradical properties; the latter was more potent in this respect. Oxidation of lipids by hydroxyl groups contained in ecdysterone can account for its antiradical effect. Ecdysterone and D3 may cause antiradical effects through the same mechanisms.

Animals↗
PubMed1998

Elevated PTH levels in hypovitaminosis D are more rapidly suppressed by the administration of 1,25-dihydroxy-vitamin D3 than by vitamin D3.

OBJECTIVE: To assess markers of bone metabolism in two groups of inpatients with hypovitaminosis D and elevated PTH levels receiving two different vitamin D medications. METHODS: 26 patients with secondary hyperparathyroidism (2 degrees HP) were treated either with 800 IU cholecalciferol and 1000 mg calcium or 0.5 microgram calcitriol plus 500 mg calcium daily for 6 months. 25-OH-vitamin D3, 1,25-dihydroxy-vitamin D3, intact PTH, calcium and urinary N-telopeptides of bone collagen I were measured at baseline, 3 and 6 months. RESULTS: PTH levels decreased earlier in the calcitriol group than in the cholecalciferol group. After six month no difference could be documented. Lowering of urinary N-telopeptides excretion was observed in both groups. CONCLUSION: The use of both forms of vitamin D supplementation appears to be useful for patients with hypovitaminosis D, elevated PTH levels and high telopeptide excretion.

Administration, Oral↗
PubMed2004

Effect of Vitamin D on falls: a meta-analysis.

CONTEXT: Falls among elderly individuals occur frequently, increase with age, and lead to substantial morbidity and mortality. The role of vitamin D in preventing falls among elderly people has not been well established. OBJECTIVE: To assess the effectiveness of vitamin D in preventing an older person from falling. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. Search terms included trial terms: randomized-controlled trial or controlled-clinical trial or random-allocation or double-blind method, or single-blind method or uncontrolled-trials with vitamin D terms: cholecalciferol or hydroxycholecalciferols or calcifediol or dihydroxycholecalciferols or calcitriol or vitamin D/aa[analogs & derivates] or ergocalciferol or vitamin D/bl[blood]; and with accidental falls or falls, and humans. STUDY SELECTION: We included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma for which the method of fall ascertainment and definition of falls were defined explicitly. Studies including patients in unstable health states were excluded. Five of 38 identified studies were included in the primary analysis and 5 other studies were included in a sensitivity analysis. DATA EXTRACTION: Independent extraction by 3 authors using predefined data fields including study quality indicators. DATA SYNTHESIS: Based on 5 RCTs involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The inclusion of 5 additional studies, involving 10 001 participants, in a sensitivity analysis resulted in a smaller but still significant effect size (corrected RR, 0.87; 95% CI, 0.80-0.96). Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men. CONCLUSIONS: Vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies examining the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and effects in men should be considered.

Accidental Falls↗
PubMed1989

Cartilage macromolecules and the calcification of cartilage matrix.

The calcification of cartilage matrix in endochondral bone formation occurs in an extracellular matrix composed of fibrils of type II collagen with which type X collagen is closely associated. Also present within this matrix are the large proteoglycans containing chondroitin sulfate which aggregate with hyaluronic acid. In addition, the matrix contains matrix vesicles containing alkaline phosphatase. There is probably a concentration of calcium as a result of its binding to the many chondroitin sulfate chains. At the time of calcification, these proteoglycans become focally concentrated in sites where mineral is deposited. This would result in an even greater focal concentration of calcium. Release of inorganic phosphate, as a result of the activity of alkaline phosphatase, can lead to the displacement of proteoglycan bound calcium and its precipitation. The C-propeptide of type II collagen becomes concentrated in the mineralizing sites, prior to which it is mainly associated with type II collagen fibrils and is present in dilated cisternae of the enlarged hypertrophic chondrocytes. The synthesis of type II collagen and the C-propeptide, together with alkaline phosphatase, are regulated by the vitamin D metabolites 24,25(OH)2 cholecalciferol and 1,25 (OH)2 cholecalciferol. At the time of calcification, type X collagen remains associated with type II collagen fibrils. It may play a role in preventing the initial calcification of these fibrils focusing mineral formation in focal interfibrillar sites. This process of calcification is clearly very complex, and involves different interacting matrix molecules and is carefully regulated at the cellular level.

Animals↗