ascorbic-acid and Fractures--Bone

This study aimed to provide reliable estimates for dietary antioxidant vitamin (vitamins A, C, and E) intake and their effect on fracture risk at various sites.. The PubMed, EMBASE, and Cochrane Library databases were searched to identify prospective cohort studies published throughout October 2019. The pooled relative risk (RR) with its 95% confidence interval (CI) was calculated using a random-effects model.. In total, 13 prospective cohort studies involving 384,464 individuals were selected for this meta-analysis. The summary RR indicated that increased antioxidant vitamin intake was associated with a reduced fracture risk (RR: 0.92; 95% CI: 0.86-0.98; P = .015). When stratified by the vitamin types, increased vitamin E intake was found to be associated with a reduced fracture risk (RR: 0.66; 95% CI: 0.46-0.95; P = .025), whereas increased vitamin A and C intake did not affect this risk. Increased antioxidant vitamin intake was associated with a reduced fracture risk, irrespective of fracture sites (HR: 0.90; 95% CI: 0.86-0.94; P < .001); however, it did not affect hip fracture risk. Furthermore, increased antioxidant vitamin intake was associated with a reduced fracture risk in men (RR: 0.81; 95% CI: 0.68-0.96; P = .017) and combined men and women (RR: 0.83; 95%CI: 0.73-0.93; P = .002); however, it did not affect fracture risk in women.. Fracture risk at any site is significantly reduced with increased antioxidant vitamin intake, especially vitamin E intake and in men.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Dietary Supplements; Female; Fractures, Bone; Hip Fractures; Humans; Male; Middle Aged; Osteoporosis; Prevalence; Prospective Studies; Risk Factors; Vitamin A; Vitamin E; Vitamins

Osteoporosis and related fractures are a major global health issue, but there are few preventative strategies. Previously reported associations between higher intakes of fruits and vegetables and skeletal health have been suggested to be partly attributable to vitamin C. To date, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention but an overall consensus of published studies has not yet been drawn. The present review aims to provide a summary of the proposed underlying mechanisms of vitamin C on bone and reviews the current evidence in the literature, examining a potential link between vitamin C intake and status with osteoporosis and fractures. The Bradford Hill criteria were used to assess reported associations. Recent animal studies have provided insights into the involvement of vitamin C in osteoclastogenesis and osteoblastogenesis, and its role as a mediator of bone matrix deposition, affecting both the quantity and quality of bone collagen. Observational studies have provided some evidence for this in the general population, showing positive associations between dietary vitamin C intake and supplements and higher bone mineral density or reduced fracture risk. However, previous intervention studies were not sufficiently well designed to evaluate these associations. Epidemiological data are particularly limited for vitamin C status and for fracture risk and good-quality randomised controlled trials are needed to confirm previous epidemiological findings. The present review also highlights that associations between vitamin C and bone health may be non-linear and further research is needed to ascertain optimal intakes for osteoporosis and fracture prevention.

Topics: Animals; Ascorbic Acid; Bone and Bones; Diet; Epidemiologic Methods; Fractures, Bone; Humans; Nutritional Status; Osteoporosis

Osteoporosis is a major health disorder associated with an increased risk of fracture. Nutrition is among the modifiable factors that influence the risk of osteoporosis and fracture. Calcium and vitamin D play important roles in improving bone mineral density and reducing the risk of fracture. Other vitamins appear to play a role in bone health as well. In this review, the findings of studies that related the intake and/or the status of vitamins other than vitamin D to bone health in animals and humans are summarized. Studies of vitamin A showed inconsistent results. Excessive, as well as insufficient, levels of retinol intake may be associated with compromised bone health. Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture. Deficiencies in vitamins C, E, and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin D. These findings highlight the importance of adequate nutrition in preserving bone mass and reducing the risk of osteoporosis and fractures.

Topics: Animals; Ascorbic Acid; Avitaminosis; Bone and Bones; Female; Fractures, Bone; Humans; Male; Nutritional Status; Osteoporosis; Osteoporosis, Postmenopausal; Vitamin A; Vitamin B Complex; Vitamin E; Vitamin K; Vitamins

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Complex regional pain syndrome type I is treated symptomatically. A protective effect of vitamin C (ascorbic acid) has been reported previously. A dose-response study was designed to evaluate its effect in patients with wrist fractures.. In a double-blind, prospective, multicenter trial, 416 patients with 427 wrist fractures were randomly allocated to treatment with placebo or treatment with 200, 500, or 1500 mg of vitamin C daily for fifty days. The effect of gender, age, fracture type, and cast-related complaints on the occurrence of complex regional pain syndrome was analyzed.. Three hundred and seventeen patients with 328 fractures were randomized to receive vitamin C, and ninety-nine patients with ninety-nine fractures were randomized to receive a placebo. The prevalence of complex regional pain syndrome was 2.4% (eight of 328) in the vitamin C group and 10.1% (ten of ninety-nine) in the placebo group (p=0.002); all of the affected patients were elderly women. Analysis of the different doses of vitamin C showed that the prevalence of complex regional pain syndrome was 4.2% (four of ninety-six) in the 200-mg group (relative risk, 0.41; 95% confidence interval, 0.13 to 1.27), 1.8% (two of 114) in the 500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.77), and 1.7% (two of 118) in the 1500-mg group (relative risk, 0.17; 95% confidence interval, 0.04 to 0.75). Early cast-related complaints predicted the development of complex regional pain syndrome (relative risk, 5.35; 95% confidence interval, 2.13 to 13.42).. Vitamin C reduces the prevalence of complex regional pain syndrome after wrist fractures. A daily dose of 500 mg for fifty days is recommended.

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Chi-Square Distribution; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fractures, Bone; Humans; Male; Middle Aged; Reflex Sympathetic Dystrophy; Treatment Outcome; Wrist Injuries

Topics: Aged; Antioxidants; Ascorbic Acid; Diagnosis, Differential; Fracture Healing; Fractures, Bone; Humans; Incidence; Randomized Controlled Trials as Topic; Reflex Sympathetic Dystrophy; Wrist Injuries

The pathogenesis of reflex sympathetic dystrophy (RSD) is not clear, nor is there a definitive treatment for this syndrome. The morbidity, costs in health care, and loss of work time justify the search for a means to prevent post-traumatic dystrophy. Although the role of toxic oxygen radicals has not yet been clarified, we investigated vitamin C (ascorbic acid) as a prophylactic antioxidant drug.. 123 adults with 127 conservatively treated wrist fractures were randomly allocated in a double-blind trial to take a capsule of 500 mg vitamin C or placebo daily for 50 days. Each participant's sex, age, side of fracture, dominance, fracture type, dislocation, reduction, and complaints with the plaster cast were recorded, and they were clinically scored for RSD. The follow-up lasted 1 year.. Eight patients were withdrawn after randomisation. 52 patients with 54 fractures (male 22%, female 78%; mean age 57 years) received vitamin C and 63 patients with 65 fractures (male 20%, female 80%; mean age 60 years) received placebo. RSD occurred in four (7%) wrists in the vitamin C group and 14 (22%) in the placebo group 15% (95% CI for differences 2-26). Other significant prognostic variables for the occurrence of RSD were complaints while wearing the cast (relative risk 0.17 [0.07-0.41]) and fracture type (0.37 [0.16-0.89]).. This prospective, double-blind study shows that vitamin C was associated with a lower risk of RSD after wrist fractures. Our hypothesis is that this beneficial effect of prophylaxis would be useful in other forms of trauma.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Casts, Surgical; Female; Fracture Healing; Fractures, Bone; Humans; Male; Middle Aged; Reflex Sympathetic Dystrophy; Wrist Injuries

In a prospective double-blind controlled trial the effect of large doses of ascorbic acid on the healing of pressure-sores has been assessed. 20 surgical patients were studied, the pressure areas being assessed by serial photography and ulcer tracings. The mean ascorbic-acid levels in treated and non-treated groups one month after the start of treatment were 65.6 and 25.8 mug per 10-8 white blood-cells. In the group treated with ascorbic acid there was a mean reduction in pressure-sore area of 84% after one month compared with 42.7% in the placebo group. These findings are statistically significant (P less than 0.005) and suggest that ascorbic acid may accelerate the healing of pressure-sores.

Topics: Aged; Arthritis, Rheumatoid; Ascorbic Acid; Ascorbic Acid Deficiency; Cerebrovascular Disorders; Clinical Trials as Topic; Female; Fractures, Bone; Humans; Leukocytes; Male; Middle Aged; Paraplegia; Postoperative Complications; Pressure Ulcer; Prospective Studies; Vascular Diseases; Wound Healing

Topics: Adult; Anxiety; Ascorbic Acid; Complex Regional Pain Syndromes; Female; Fractures, Bone; Humans; Metatarsal Bones; Pain Management; Physical Therapy Modalities; Treatment Outcome

Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain.. We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study.. Serum vitamin D concentrations were measured in 14,641 men and women aged 42-82 y in 1997-2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥ 90 nmol/L.. The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers.. Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate increase in population mean concentrations may have potential health benefit, but <1% of the population had concentrations >120 nmol/L.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Body Mass Index; Cardiovascular Diseases; Female; Fractures, Bone; Humans; Incidence; Male; Middle Aged; Motor Activity; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Respiratory Tract Diseases; Socioeconomic Factors; United Kingdom; Vitamin D; Vitamin D Deficiency

The study was aimed at performing an experimental trial of the reparative osteogenesis stimulation by local injection of autologous plasma in combination with metabolically active substances such as L-ascorbic acid and D-glucose for management of pelvic fractures.. The experiment was carried out on twenty-six mongrel dog of both sexes aged 1.5 ± 0.09 years and with body weight of 17 ± 0.5kg. Transverse osteotomy was performed in the acetabulum (n = 20) and in the ilium body (n = 6). The fractures were stabilized with external fixators. On days two through 5 after the operation all dogs had intraarticular or intraosseous injections of the saline solution throughout 24 hours in the dose of 0.4 ml per day. Experimental animals were additionally injected once a day with 1 ml of a composition consisting of the ascorbic acid and glucose. The external apparatuses were dismounted on day 21 after the operation. The animals for histological study were euthanized on day 14 and 42 after the operation. The study used radiographic and histological methods of study as well as the method of radiographic electron probe microanalysis.. The control animals that had either intraosseous or intraarticular saline injections alone had fibro-cartilaginous union of the pelvic fragments. They developed bone deformity due to secondary displacement upon apparatus removal. The experimental animals had primary bone union on day 14. The bone was consolidated after the removal of the apparatus.. Autologous blood plasma in combination with active substances of ascorbic acid and glucose had a marked stimulating effect on pelvic fracture healing if applied locally in the posttraumatic period. The method of reparative osteogenesis stimulation that was developed is low traumatic. It does not hinder early functional loading and allows control of reparative process basing on the biological principles of tissue regeneration.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Dogs; Drug Administration Routes; Fracture Fixation, Internal; Fracture Healing; Fractures, Bone; Glucose; Pelvic Bones; Plasma; Treatment Outcome

There is little evidence regarding the associations between bone growth and environmental factors among growing children, especially in Asians. The aim of this cross-sectional study was to search for the promotion factors of bone growth in Japanese children during growth. The study subjects were male (n=333) and pre/post-menarcheal female (n=179/n=68) school children aged 8-14 y. Bone status at the calcaneus was evaluated by quantitative ultrasound (Benus III), and the bone area ratio (BAR) was used as an evaluation index. Dietary intakes were assessed via brief self-administered diet history questionnaires. The participants were asked to record all of their activities for 3 d (2 weekdays and 1 holiday). They were also required to provide the most recent anthropometric measurement records at their schools and answer questions about the frequency of fractures and, for females, the length of time since menarche. Multiple regression analysis with dummy variables demonstrated that age, magnesium (more than the RDA), vitamin B(1) (more than the RDA), mean physical activity intensity per day (more than 1.7 METs), vitamin C (more than the RDA) and calcium (more than the RDA) were significantly positive influential factors of BAR for males. For premenarcheal females, age, vitamin A (more than the RDA), BMI, and mean physical activity intensity per day (more than 1.7 METs) were significantly positive influential factors of BAR, and for postmenarcheal females, only BMI and age were significantly positive influential factors of BAR. The results suggest that several manageable factors correlate with the bone mass, and the associations differ depending on gender and menarcheal status.

Topics: Adolescent; Anthropometry; Ascorbic Acid; Asian People; Body Mass Index; Bone Density; Calcaneus; Calcium, Dietary; Child; Cross-Sectional Studies; Diet; Energy Intake; Female; Fractures, Bone; Humans; Magnesium; Male; Menarche; Motor Activity; Nutrition Assessment; Regression Analysis; Sex Factors; Surveys and Questionnaires; Thiamine; Ultrasonography; Vitamin A

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Fractures, Bone; Humans; Scurvy

Complex regional pain syndrome (CRPS) is the complication of some injuries, such as a fracture, which affects the distal end of the injured extremity characterized by pain, allodynia, hyperalgesia, edema, abnormal vasomotor and sudomotor activity, movement disorders, joint stiffness, regional osteoporosis, and dystrophic changes in soft tissue. Exact pathogenic mechanism of CRPS is still unclear. Suggested pathogenic mechanisms of CRPS are evaluated in four major groups consist of classic inflammation, hypoxic changes and chronic ischemia, neurogenic inflammation and sympathetic dysregulation. All of these suggested pathogenic mechanisms produced by inflammatory cytokines mediated by nuclear factor kappaB. Vitamin K is a family of structurally similar, fat-soluble, 2-methyl-1,4-naphthoquinones. Vitamin K exerts a powerful influence on bone formation, especially in osteoporosis. Fat in bone stores some vitamin K. Gamma-carboxylation of the glutamic acid in osteocalcin is vitamin K dependent. Osteocalcin plays a role in calcium uptake and bone mineralization. Osteocalcin, the most abundant non-collagenous protein in bone, is produced by osteoblasts during bone matrix formation. Because osteocalcin is not carboxylated in case of vitamin K deficiency at the distal site of fracture or injury, it cannot bind to hydroxyapatite causing osteoporosis. Fracture starts a local inflammatory process in the fracture site and adjacent tissues as seen in CRPS. Vitamin K was shown to suppress the inflammatory cytokines and NF-kappaB and prevent oxidative, hypoxic, ischemic injury (which have key role in both initiation and progression of CRPS) to oligodendrocytes and neurons. We hypothesized that vitamin K has a key role and modulatory effect in CRPS pathogenesis. Vitamin K deficiency at the distal site of fracture occurs because of diminished and slowed circulation, local immobilization after extremity fracture or injury and use of vitamin K store at the distal site of the injured extremity and in the circulation for fracture healing and bone remodelling. In case of vitamin K deficiency at the distal site of fracture, classic inflammation starts with fracture at the distal tissues could not be restricted and classic inflammation, hypoxic changes, chronic ischemia, neurogenic inflammation, sympathetic dysregulation, which are the pathogenic mechanisms of CRPS, and patchy osteoporosis which occur due to high level of under-carboxylated osteocalcin could not be prevented. Br

Topics: Ascorbic Acid; Blood Coagulation; Complex Regional Pain Syndromes; Cytokines; Fracture Healing; Fractures, Bone; Humans; Intestinal Absorption; NF-kappa B; Osteocalcin; Osteogenesis; Osteoporosis; Vitamin K

Staphylococcal enterotoxin C injection is established as a clinical therapy for delayed healing or disunion of bone fractures. In the present study, the effects of staphylococcal enterotoxin C injection in combination with ascorbic acid (SEC-AA) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) and their influences on the mineralization of osteoblasts were investigated. SEC-AA treatment induced increased levels of alkaline phosphatase activity in MSCs and increased numbers of alizarin red-stained calcified nodules, indicating enhanced differentiation of MSCs into osteoblasts. The findings demonstrated that SEC-AA promoted the differentiation of MSCs into osteoblasts and accelerated the cytopoiesis of osteoblasts. Our data provide a cytological model for bone fracture therapy aimed at shortening the time required for healing and improving the clinical outcome, and also provide a theoretical basis for inducible differentiation of MSCs, mineralization of osteoblasts and reconstruction of bone tissues.

Topics: Alkaline Phosphatase; Animals; Anthraquinones; Ascorbic Acid; Bone Marrow; Calcification, Physiologic; Cell Differentiation; Enterotoxins; Flow Cytometry; Fractures, Bone; Mesenchymal Stem Cells; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Osteoblasts; Rats; Rats, Sprague-Dawley

Topics: Adult; Ascorbic Acid; Calcium; Cholecalciferol; Female; Fractures, Bone; Humans; Hypocalcemia; Osteomalacia; Pregnancy; Pregnancy Complications; Vitamin D Deficiency

Topics: Animals; Ascorbic Acid; Fractures, Bone; Humans; Incidence; Rats; Reflex Sympathetic Dystrophy; Vitamins; Wrist Injuries

Water-soluble vitamins influence the development of an adequate structure of bone tissue, but there is scant information relating them with osteoporotic fractures. We analyze whether serum vitamin C, vitamin B12, and erythrocyte folate, or dietary intake of vitamin C and folate, are related with osteoporotic fractures in the elderly. A hospital-based case-control study was carried out at the Hospital of Jaén (167 cases, 167 controls), Spain. Cases were defined as patients aged 65 or more years with a low-energy fracture. Controls were people without fracture, matched for age and sex with cases. Diet was assessed by a semi-quantitative food frequency questionnaire. Serum vitamin C was measured using high-performance liquid chromatography (HPLC). Folic acid and vitamin B12 were measured using procedures of competitive or immunometric immunoassay. Multivariable analyses were also fitted to adjust for confounding using analysis of covariance (for the comparison of adjusted means) and conditional logistic regression (for estimating adjusted odds ratios). A statistically significant difference between cases and controls for vitamin C blood levels was found, being higher for controls (p = 0.01). Analysis of the association between serum vitamin C and fracture risk showed a linear trend (p = 0.03) with a significantly reduced risk for the upper quartile (OR = 0.31; 95% CI 0.11-0.87). The intake of vitamin C, folic acid, and B12 was not related to fracture risk, nor was there any association with erythrocyte folate or serum vitamin B12. In conclusion, serum vitamin C levels were lower in cases with osteoporotic fractures than in controls.

Topics: Aged; Aging; Ascorbic Acid; Case-Control Studies; Causality; Chromatography, High Pressure Liquid; Diet; Diet Records; Female; Folic Acid; Fractures, Bone; Geriatric Assessment; Humans; Immunoassay; Male; Multivariate Analysis; Odds Ratio; Osteoporosis; Risk Factors; Spain; Surveys and Questionnaires; Vitamin B 12

Restless legs syndrome is a common condition that results in difficulties falling and staying asleep and perception of poor sleep quality. We report a case of a 73-year-old woman with uncontrolled restless legs syndrome who spent most of the night standing and walking. As a result of her nighttime behaviors, she fell several times and sustained, on several separate occasions, fractures of both forearms, ribs, and nose. Iron replacement therapy and changing of her dopamine-agonist medications resulted in almost complete relief of symptoms. Physicians should be aware of the potential for injury in patients with uncontrolled RLS.

Topics: Accidental Falls; Aged; Ascorbic Acid; Continuous Positive Airway Pressure; Drug Therapy, Combination; Female; Ferrous Compounds; Fractures, Bone; Humans; Multiple Trauma; Restless Legs Syndrome; Trace Elements; Treatment Outcome

Topics: Ascorbic Acid; Complex Regional Pain Syndromes; Fractures, Bone; Humans; Vitamins; Wrist Injuries

Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures.. A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age.. Skeletal phenotype of the sfx phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay.. Femur and tibial BMD were reduced by 27% and 36%, respectively, in sfx mice at 5 weeks of age. Histomorphometric analyses of bones from sfx mice revealed that bone formation rate is reduced by >90% and is caused by impairment of differentiated functions of osteoblasts. The sfx gene was fine mapped to a 2 MB region containing approximately 30 genes in chromosome 14. By using various molecular genetic approaches, we identified that deletion of the gulonolactone oxidase (GULO) gene, which is involved in the synthesis of ascorbic acid, is responsible for the sfx phenotype. We established that ascorbic acid deficiency caused by deletion of the GULO gene (38,146-bp region) contributes to fractures and premature death because the sfx phenotype can be corrected in vivo by treating sfx mice with ascorbic acid and because osteoblasts derived from sfx mice are only able to form mineralized nodules when treated with ascorbic acid. Treatment of bone marrow stromal cells derived from sfx/sfx mice in vitro with ascorbic acid increased expression levels of type I collagen, alkaline phosphatase, and osteocalcin several-fold.. The sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, we propose that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Bone Marrow Cells; Cell Differentiation; Chromosome Mapping; Densitometry; DNA Primers; DNA, Complementary; Femur; Fracture Healing; Fractures, Bone; Gene Deletion; Genome; Genotype; L-Gulonolactone Oxidase; Mice; Mice, Inbred BALB C; Models, Genetic; Mutation; Oligonucleotide Array Sequence Analysis; Osteoblasts; Osteoporosis; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA; Stromal Cells; Tibia; X-Rays

Although recent epidemiological studies found a positive correlation between dietary vitamin C intake and bone mineral density, data on plasma levels of vitamin C or other antioxidants in osteoporotic subjects are scanty. The aim of this study was to evaluate whether antioxidant defenses are decreased in elderly osteoporotic women and, if this is the case, to understand whether osteoporosis is a condition characterized by increased oxidative stress. To answer these questions, plasma vitamins C, E, and A; uric acid; and the enzymatic activities of superoxide dismutase in plasma and erythrocytes and of glutathione peroxidase in plasma were measured in 75 subjects with osteoporosis and 75 controls. Dietary and endogenous antioxidants were consistently lower in osteoporotic than in control subjects. On the other hand, plasma levels of malondialdehyde, a byproduct of lipid peroxidation, did not differ between groups. Our results reveal that antioxidant defenses are markedly decreased in osteoporotic women. The mechanisms underlying antioxidant depletion and its relevance to the pathogenesis of osteoporosis deserve further investigation.

Topics: Activities of Daily Living; Aged; Aging; Antioxidants; Ascorbic Acid; Body Mass Index; Bone and Bones; Cross-Sectional Studies; Diet; Erythrocytes; Female; Fractures, Bone; Glutathione Peroxidase; Humans; Lipid Peroxidation; Malondialdehyde; Middle Aged; Osteoporosis; Superoxide Dismutase; Uric Acid; Vitamin A; Vitamin E

The benefits of various minerals and vitamins on fracture healing have been demonstrated in animal models. Vitamin C is an essential substance in fracture healing but has not been studied previously on an experimental basis. Sixteen rats were grouped randomly into control and vitamin C-supplemented groups. The right tibias of all rats were fractured by digital manipulation. One group received single high dose of vitamin C intramuscularly. On the 5th, 10th, 15th, and 20th days, two rats from each group were killed and the tibias examined under light microscopy. It was seen that the vitamin C-supplemented group went through the stages of fracture healing faster compared with the control group.

Topics: Animals; Ascorbic Acid; Fracture Healing; Fractures, Bone; Rats; Rats, Wistar

Ascorbic acid is an essential nutrient involved in collagen formation, and its deficiency is associated with abnormal bone development. To examine the relation of ascorbic acid to bone mineral density and the prevalence of self-reported fractures, the authors analyzed data collected from 13,080 adults enrolled in the Third National Health and Nutrition Examination Survey (NHANES III) during 1988-1994. Because they identified three-way interactions among smoking, history of estrogen use, and dietary and serum ascorbic acid in postmenopausal women, they analyzed these relations stratified by smoking and estrogen use. Dietary ascorbic acid intake was independently associated with bone mineral density among premenopausal women (p = 0.002). Among men, serum ascorbic acid was associated in a nonlinear fashion with bone mineral density (p < 0.05), and dietary ascorbic acid intake was associated in a nonlinear fashion with self-reported fracture (p = 0.05). Among postmenopausal women without a history of smoking or estrogen use, serum ascorbic acid was unexpectedly associated with lower bone mineral density (p = 0.01). However, among postmenopausal women with a history of smoking and estrogen use, a standard deviation increase in serum ascorbic acid was associated with a 49% decrease in fracture prevalence (p = 0.001). Dietary and serum ascorbic acid measures were associated inconsistently with bone mineral density and self-reported fracture among adult participants in NHANES III.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Bone Density; Data Interpretation, Statistical; Female; Fractures, Bone; Humans; Male; Middle Aged; Nutrition Surveys; Prevalence; Risk Factors; United States

Topics: Ascorbic Acid; Body Mass Index; Bone Density; Case-Control Studies; Cohort Studies; Data Collection; Fractures, Bone; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Osteoporosis; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Time Factors

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Double-Blind Method; Female; Fractures, Bone; Free Radical Scavengers; Humans; Immobilization; Male; Middle Aged; Randomized Controlled Trials as Topic; Reflex Sympathetic Dystrophy; Reproducibility of Results; Treatment Outcome; Wrist Injuries

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Fractures, Bone; Humans; Middle Aged; Randomized Controlled Trials as Topic; Reflex Sympathetic Dystrophy; Wrist Injuries

As fracture is known to occur more easily in severely handicapped children (SHC), bone mineral content, serum zinc level and serum vitamin C level were determined in 65 SHC. These parameters were found to be greatly reduced in all patients. The decreases in zinc and vitamin C in the serum appeared to be associated with that in bone mineral content. Supplements of zinc and vitamin C may be important to decrease the chance of fracture due to diminished bone mineral content in SHC.

Topics: Adolescent; Adult; Ascorbic Acid; Bone Density; Disabled Persons; Female; Fractures, Bone; Humans; Intellectual Disability; Male; Zinc

Traumatic sacral fractures are most often due to motor vehicle or industrial accidents and are commonly associated with pelvic, urogenital, and neurological injuries. In recent years, a more subtle type of sacral fracture, not associated with major trauma, has been described. It is an osteoporotic insufficiency fracture that presents as low back pain in elderly patients, especially postmenopausal Caucasian women. It may escape detection unless radionuclide bone scans, tomograms, or computed tomograms are obtained. The radiographic features have been detailed in various publications, but little has been reported about the clinical features, treatment, or ultimate outcome of patients with osteoporotic sacral fractures. We have reviewed the charts and radiological studies of 13 women and 3 men who sustained this type of fracture between 1983 and 1986. All of these patients were Caucasian. The average age was 71 years. The most common presenting symptom complex was diffuse low back pain accompanied by hip, buttock, or thigh pain. Pertinent physical findings were limited to tenderness on palpation of the sacrum and a decreased range of low back motion. The osteoporotic fractures were seldom noted on plain roentgenograms of the sacrum, but were readily defined by sacral tomography or computed tomography. Radionuclide bone scanning also proved helpful in making the diagnosis by localizing the process. Treatment was medical and consisted of therapies designed to reduce pain and to combat the associated osteopenia. Of our 16 patients, 11 had complete pain relief, 2 had substantial pain relief, 2 noted decreasing pain before they died of other causes, and 1 was followed less than 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Estrogens; Female; Fracture Fixation; Fractures, Bone; Humans; Male; Middle Aged; Osteoporosis; Palliative Care; Radionuclide Imaging; Sacrum; Tomography, X-Ray Computed; Vitamin D

Topics: Adolescent; Adult; Ascorbic Acid; Back Pain; Bone Diseases; Child; Fractures, Bone; Humans; Muscular Diseases; Neoplasms; Osteogenesis Imperfecta; Pain

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Calcium Gluconate; Combined Modality Therapy; Femoral Fractures; Fibula; Fractures, Bone; Fractures, Closed; Gluconates; Humans; Injections; Middle Aged; Thiamine; Tibial Fractures; Traction

Ascorbic acid intake of sixty-seven patients with myelomeningocele, ages one through eight years, was evaluated in two groups, fracture and non-fracture, to compare their intake of ascorbic acid from food-plus-supplement, food-only, and supplement-only with the recommended allowances. Intake from food-plus-supplement exceeded the allowance for 90 per cent of the fracture and 83 per cent of the non-fractured patients. Intake from food-only exceeded the recommended allowance in 79 per cent of the fracture and 75 per cent of the non-fracture subjects. All supplementations exceeded 100 per cent of the recommended allowance. There was no significant difference in the ascorbic acid intakes of fracture and non-fracture patients. Since there was no apparent correlation between fractures and ascorbic acid intake, we do not recommend ascorbic acid supplementation to prevent fractures. If such high levels are suggested, the potentially harmful effects of excessive ascorbic acid in growing children must be carefully considered.

Topics: Adolescent; Ascorbic Acid; Bone and Bones; Child; Child, Preschool; Fractures, Bone; Humans; Infant; Leg Injuries; Meningomyelocele; Nutritional Requirements; Spinal Dysraphism

Topics: Administration, Oral; Adolescent; Ascorbic Acid; Child; Child, Preschool; Female; Fractures, Bone; Humans; Infant; Infant, Newborn; Male; Osteogenesis Imperfecta; Zinc

Topics: Animals; Ascorbic Acid; Burns; Collagen; Evaluation Studies as Topic; Follow-Up Studies; Fractures, Bone; Guinea Pigs; Male; Prognosis; Radiography; Wound Healing

Topics: Alkaline Phosphatase; Amino Acids; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Collagen; Fishes; Fractures, Bone; Hydroxyproline; Pigmentation Disorders; Radiography; Scurvy; Spinal Diseases; Spine

Topics: Ascorbic Acid; Atrophy; Body Temperature Regulation; Burns; Fractures, Bone; Glycosuria; Humans; Hyperglycemia; Muscle Proteins; Nutritional Physiological Phenomena; Proteins; Wounds and Injuries

Topics: Animals; Ascorbic Acid; Blood Proteins; Female; Fractures, Bone; Male; Rabbits; Wound Healing

Topics: Animals; Ascorbic Acid; Calcium; Fractures, Bone; Rats; Research; Thyroxine; Wound Healing

Topics: Anabolic Agents; Animals; Ascorbic Acid; Calcium; Cissus; Collagen; Dogs; Fracture Healing; Fractures, Bone; Glycosaminoglycans; Plants, Medicinal; Radius Fractures; Rats; Research; Steroids; Ulna; Wound Healing

Topics: Ascorbic Acid; Bone and Bones; Calcification, Physiologic; Calcium; Calcium Isotopes; Cissus; Collagen; Fractures, Bone; Glycosaminoglycans; Metabolism; Phosphorus; Plants, Medicinal; Rats; Research; Steroids; Strontium; Sulfur

Topics: Ascorbic Acid; Bone and Bones; Calcium; Collagen; Fractures, Bone; Gluconates; Glycosaminoglycans; Histocytochemistry; Rats; Research; Wound Healing

Topics: Ascorbic Acid; Bone and Bones; Calcium; Collagen; Fractures, Bone; Glycosaminoglycans; Metabolism; Methandrostenolone; Pharmacology; Rats; Research; Wound Healing

Topics: Ascorbic Acid; Bone Diseases; Calcinosis; Diagnosis, Differential; Ergocalciferols; Fractures, Bone; Humans; Infant; Osteoporosis; Radiography; Rickets; Scurvy; Streptomycin; Vitamin A

Topics: Adrenal Cortex Hormones; Ascorbic Acid; Blood; Fracture Healing; Fractures, Bone; Metabolism; Physiology; Plasma; Rats; Research; Wound Healing

Topics: Anabolic Agents; Animals; Ascorbic Acid; Bone and Bones; Fractures, Bone; Humans; Lordosis; Metabolism; Osteoporosis; Pseudarthrosis; Steroids

Topics: Ascorbic Acid; Fracture Healing; Fractures, Bone; Humans; Vitamins