Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis.

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50-125 nmol/L, requiring 600-4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50-125 nmol/L (600-4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Vitamin D, bone mineral density and risk of fracture in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. METHOD: We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. RESULTS: Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P < 0.0001), respectively. Thirty-six participants underwent a dual-energy X-ray absorptiometry scan, which showed osteoporosis in 23.7% and osteopenia in 52.6%. Participants on vitamin D had higher BMD than those who were not, a statistically significant difference when confounders (lack of mobility and hypogonadism) were removed. BMD was significantly different according to mobility, particularly in wheelchair users, in whom hip BMD was 33% lower (P < 0.0001) than in participants with normal mobility. Participants still taking vitamin D showed a 6.1% increase in BMD at the spine (P = 0.003) after mean [SD] 7.4 [1.5] years vitamin D treatment. CONCLUSIONS: In people with IDs and previous vitamin D deficiency, BMD increases on long-term vitamin D supplementation. However, additional strategies must be considered for osteoporosis and fracture prevention in this population.

Multiple unexplained fractures in infants and child physical abuse.

When an infant presents with X-rays showing multiple unexplained fractures in various stages of healing (MUFVSH), the child is usually diagnosed with child abuse based on criteria of the Academy of Pediatrics' Committee on Child Abuse and Neglect (AAPCCAAN). Almost always, the infant is subsequently removed from the home and civil or criminal proceeding commence. It may be that healing infantile rickets or other poorly understood metabolic bone disorders of infancy are responsible for these x-rays. Activated vitamin D is a seco-steroid hormone, whose mechanism of action is genetic regulation. Lack of it can result in musculoskeletal defects known as rickets. Low calcium can also cause rickets. However, it is clear that experts for the state believe that the x-rays in these cases are so definitive as to be pathognomonic for child abuse. Therefore, if the caregivers deny abusing their infants, experts following American Academy of Pediatric's Committee on Child Abuse and Neglect. guidelines are essentially claiming that x-rays showing multiple unexplained fractures in various stages of healing are lie detector tests. However, it is not widely appreciated that the gold standard for the diagnosis of rickets is a bone biopsy, not x-rays, as radiologists miss biopsy proven rickets 80% of the time; that is, 4 out of 5 infants with rickets will have normal x-rays. In this article we provide reports of two cases and their outcomes. We discuss information about healing infantile rickets and an example of common sense medical conclusions in these cases. This information could lead to a significant reduction in the number of innocent parents having their infant removed or sent to prison.

The variation in urinary calcium levels in adult patients with fracture and surgical intervention.

BACKGROUND: Generally, a higher calcium diet is fed to fracture patients after surgery. However, recent studies have indicated that higher dietary calcium intakes increase the risk of urinary stones for fracture patients. Therefore, this study aimed to observe the variation in urinary calcium levels among fracture patients who underwent surgery, based on fracture type, fracture location, age and gender. METHODS: A total of 768 subjects were enrolled in this study from 2012 to 2015 and were divided into 2 groups: group A (fracture patients who underwent surgery) and group B (normal patients without fracture). Urine samples were collected for a 24-h period (24-h urine), at multiple specific time points before and after surgery for group A, or after hospitalisation for group B. Subsequently, urine calcium was detected and the changes were evaluated according to fracture location, fracture type, age and gender, as well as the distribution of hypercalciuria. RESULTS: Compared with group B, the level of urine calcium in group A significantly increased at different time points during the study period (P < 0.05). There were significant differences in the changes in urine calcium levels according to fracture location, fracture type and age, but not gender. Further, there were more patients with hypercalciuria in group A at the different time points, compared with group B. CONCLUSION: Variation in urinary calcium among fracture patients that underwent surgery was of a regular pattern and hypercalciuria was also found in these patients. Therefore, a high-calcium diet and calcium supplements should be used with caution in this patient population.

[PREPARATIONS OF PAMIDRONOVIC ACID IN COMPLEX TREATMENT ON OSTEOGENESIS IMPERFECTA].

Modern view of drug therapy in the complex treatment of orthopedic manifestations of osteogenesis imperfecta (OI) was submitted. Developed and tested system of drug correction of structural and functional state of bone tissue (BT) using drugs pamidronovic acid, depending on osteoporosis severity and type of disease. Such therapy is appropriate to apply both independently and in conjunction with surgery to correct deformations of long bones of the lower extremities. Effectiveness and feasibility of the proposed methods of drug therapy was proved, most patients resume features walking and support.

Calcium intake and risk of fracture: systematic review.

OBJECTIVE: To examine the evidence underpinning recommendations to increase calcium intake through dietary sources or calcium supplements to prevent fractures. DESIGN: Systematic review of randomised controlled trials and observational studies of calcium intake with fracture as an endpoint. Results from trials were pooled with random effects meta-analyses. DATA SOURCES: Ovid Medline, Embase, PubMed, and references from relevant systematic reviews. Initial searches undertaken in July 2013 and updated in September 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials or cohort studies of dietary calcium, milk or dairy intake, or calcium supplements (with or without vitamin D) with fracture as an outcome and participants aged >50. RESULTS: There were only two eligible randomised controlled trials of dietary sources of calcium (n=262), but 50 reports from 44 cohort studies of relations between dietary calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For dietary calcium, most studies reported no association between calcium intake and fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm fracture). For milk (25/28) and dairy intake (11/13), most studies also reported no associations. In 26 randomised controlled trials, calcium supplements reduced the risk of total fracture (20 studies, n=58,573; relative risk 0.89, 95% confidence interval 0.81 to 0.96) and vertebral fracture (12 studies, n=48,967. 0.86, 0.74 to 1.00) but not hip (13 studies, n=56,648; 0.95, 0.76 to 1.18) or forearm fracture (eight studies, n=51,775; 0.96, 0.85 to 1.09). Funnel plot inspection and Egger's regression suggested bias toward calcium supplements in the published data. In randomised controlled trials at lowest risk of bias (four studies, n=44,505), there was no effect on risk of fracture at any site. Results were similar for trials of calcium monotherapy and co-administered calcium and vitamin D. Only one trial in frail elderly women in residential care with low dietary calcium intake and vitamin D concentrations showed significant reductions in risk of fracture. CONCLUSIONS: Dietary calcium intake is not associated with risk of fracture, and there is no clinical trial evidence that increasing calcium intake from dietary sources prevents fractures. Evidence that calcium supplements prevent fractures is weak and inconsistent.

Knowledge change regarding osteoporosis prevention: translating recommended guidelines into user-friendly messages within a community forum.

BACKGROUND: Osteoporosis is a skeletal disorder characterised by low bone mineral density and increased fracture risk. Nationally the total costs of this chronic disease are currently estimated at $2.754 billion annually. Effective public health messages providing clear recommendations are vital in supporting prevention efforts. This research aimed to investigate knowledge change associated with the translation of preventive guidelines into accessible messages for the community. FINDINGS: We delivered a community-based information session that translated recommended guidelines for osteoporosis prevention into lay terms; items focused on dietary calcium, vitamin D, physical activity, alcohol, smoking and general osteoporosis-related knowledge. We developed a 10-item questionnaire reflecting these key points (score range 0-10) and investigated knowledge change associated with the session. Pre- and post-test questionnaires were completed by 47 participants (51% female), aged 21-94 years. Relatively high pre-test scores were observed for questions regarding sedentary activity and calcium intake. The lowest pre-test scores were observed for the item concerning whether swimming and cycling strengthened bones, and the highest possible score post-test was achieved for three of the items: calcium-rich food as a protective factor, and excessive alcohol and smoking as risk factors. The overall increase in knowledge change was a mean score of +2.08 (95%CI 1.58-2.42). CONCLUSIONS: An increase in knowledge regarding osteoporosis prevention was demonstrated over the short-term. Our findings suggest that the guidelines concerning dietary calcium are generally well understood; however, the asymptomatic nature of osteoporosis and the types of physical activity that assist with bone strength are less well understood.

SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells contributes to bone fracture healing.

CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived-factor 1 (SDF-1). SDF-1/CXCR4 interaction is reported to play an important role in vascular development. On the other hand, the therapeutic potential of endothelial progenitor cells (EPCs) in fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement at sites of fracture. The purpose of this study was to investigate the influence of the SDF-1/CXCR4 pathway in Tie2-lineage cells (including EPCs) in bone formation. We created CXCR4 gene conditional knockout mice using the Cre/loxP system and set two groups of mice: Tie2-Cre(ER) CXCR4 knockout mice (CXCR4(-/-) ) and wild-type mice (WT). We report here that in vitro, EPCs derived from of CXCR4(-/-) mouse bone marrow demonstrated severe reduction of migration activity and EPC colony-forming activity when compared with those derived from WT mouse bone marrow. In vivo, radiological and morphological examinations showed fracture healing delayed in the CXCR4(-/-) group and the relative callus area at weeks 2 and 3 was significantly smaller in CXCR4(-/-) group mice. Quantitative analysis of capillary density at perifracture sites also showed a significant decrease in the CXCR4(-/-) group. Especially, CXCR4(-/-) group mice demonstrated significant early reduction of blood flow recovery at fracture sites compared with the WT group in laser Doppler perfusion imaging analysis. Real-time RT-PCR analysis showed that the gene expressions of angiogenic markers (CD31, VE-cadherin, vascular endothelial growth factor [VEGF]) and osteogenic markers (osteocalcin, collagen 1A1, bone morphogenetic protein 2 [BMP2]) were lower in the CXCR4(-/-) group. In the gain-of-function study, the fracture in the SDF-1 intraperitoneally injected WT group healed significantly faster with enough callus formation compared with the SDF-1 injected CXCR4(-/-) group. We demonstrated that an EPC SDF-1/CXCR4 axis plays an important role in bone fracture healing using Tie2-Cre(ER) CXCR4 conditional knockout mice.

Is there a role for vitamin C in preventing osteoporosis and fractures? A review of the potential underlying mechanisms and current epidemiological evidence.

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.

Vitamin D: present and future / Vitamina D: presente y futuro

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Vitamina D: presente y futuro / Vitamin D: present and future

En los últimos años se ha producido un creciente interés por la vitamina D, no solo por su importante papel en el metabolismo mineral óseo, sino también por sus efectos extraóseos. La mayoría de las sociedades científicas consideran que los depósitos son suficientes si la concentración plasmática de 25-OH vitamina D está por encima de 30ng/ml y deficientes si están por debajo de 20ng/ml. La mayoría de los estudios encuentran que los suplementos de calcio más vitamina D tienen un efecto positivo en la reducción del riesgo de fractura en un 20% aproximadamente y del riesgo de caída en los ancianos, y las dosis deberían ser de 700-1.000 UI diarias. El tratamiento del déficit se puede realizar con vitamina D2, D3 o sus metabolitos activos como el calcidiol o el calcitriol. En ciertas patologías también puede utilizarse los activadores selectivos del receptor de la vitamina D (AU)

In recent years has been a growing interest by vitamin D, not only for its important role in the bone mineral metabolism, but also by the extra-osseous effects. Most of the scientific societies consider that deposits are sufficient if the serum concentration of 25-OH vitamin D is above 30ng/ml and are considered deficient if levels are below 20ng/ml. The majority of studies found that supplements of calcium plus vitamin D have a positive effect in reducing the risk of fracture and the risk of falls in the elderly, although several specifies that doses should be 700-1.000 IU daily. The treatment of the deficit can be performed with vitamin D2, D3 as well as calcidiol or the active metabolite calcitriol. In certain pathologies also selective vitamin D receptor activators can be used (AU)

Effectiveness of oral nutritional supplementation for older women after a fracture: rationale, design and study of the feasibility of a randomized controlled study.

BACKGROUND: Malnutrition is a problem for many older people recovering from a hip and other major fractures. Oral supplementation with high calorie high protein nutrients is a simple intervention that may help older people with fractures to improve their recovery in terms of rehabilitation time, length of hospital stay and mortality. This paper reports a pilot study to test the feasibility of a trial initiated in a hospital setting with an oral supplement to older people with recent fractures. METHOD: A randomized controlled trial with 44 undernourished participants admitted to a hospital following a fracture. The intervention group (n = 23) received a high calorie high protein supplement for forty days in addition to their diet of choice. The control group (n = 21) received high protein milk during their hospital stay in addition to their diet of choice and their usual diet when discharged from hospital. RESULTS: All participants were women and their mean age was 85.3 (± 6.1) years. Twenty nine (65%) participants had a hip fracture. At baseline no differences were measured between the two groups regarding their nutritional status, their cognitive ability or their abilities in activities of daily living. There were no significant differences between the intervention and control group with reference to nutritional or functional parameters at 40 day and 4 month follow-ups. Median length of stay in hospital was 18.0 days, with 12 participants being readmitted for a median of 7.0 days. CONCLUSION: It is feasible to perform a randomised trial in a hospital and community setting to test the effect of an oral high energy high protein supplement for older people. Due to the limited number of participants and incomplete adherence with use of the supplements no conclusion can be drawn about the efficacy or effectiveness of this intervention.

Vitamina D y fracturas en el anciano / Vitamin D and fractures in the elderly

La osteoporosis y las consecuentes fracturas que se producen son una fuente de morbilidad y mortalidad en la población anciana. Además, en muchas ocasiones es el inicio de la cascada que desemboca en la fragilidad y en la dependencia. La vitamina D tiene relación directa con la aparición de osteoporosis y con el riesgo de fracturas. Además, recientemente se han descrito receptores de esta vitamina en otros órganos y sistemas del cuerpo que la relacionan con la fuerza muscular, el cáncer y la mortalidad global. En nuestra población anciana, el déficit de esta vitamina es muy prevalente, tanto en la comunidad como en ancianos hospitalizados. El diagnóstico y el tratamiento son fáciles y baratos. Además, su eficacia en la prevención de la osteoporosis y en la aparición de fracturas está sobradamente demostrada. En esta revisión pretendemos repasar la fisiología y las acciones de esta vitamina, así como los principales estudios que demuestran su efectividad en la población anciana(AU)

Osteoporosis and the subsequent fractures caused by this are a source of morbidity and mortality in the elderly population. It is also often the start of the cascade that culminates in frailty and dependence. Vitamin D has a direct relationship with the appearance of osteoporosis and with the risk of fractures. Receptors of this vitamin have also recently been described in other organs and systems of the body that are associated with muscle strength, cancer and overall mortality. Deficiency of this vitamin in the elderly population in Spain is very prevalent, both in the community and the hospitalised elderly. The diagnosis and treatment are straightforward and cheap. Its efficacy in the prevention of osteoporosis and in the appearance of fractures is perfectly demonstrated. In this review, we will look at the physiology and actions of this vitamin, as well as the principal studies that have demonstrated its effectiveness in the elderly population(AU)

Dietary patterns associated with fall-related fracture in elderly Japanese: a population based prospective study.

BACKGROUND: Diet is considered an important factor for bone health, but is composed of a wide variety of foods containing complex combinations of nutrients. Therefore we investigated the relationship between dietary patterns and fall-related fractures in the elderly. METHODS: We designed a population-based prospective survey of 1178 elderly people in Japan in 2002. Dietary intake was assessed with a 75-item food frequency questionnaire (FFQ), from which dietary patterns were created by factor analysis from 27 food groups. The frequency of fall-related fracture was investigated based on insurance claim records from 2002 until 2006. The relationship between the incidence of fall-related fracture and modifiable factors, including dietary patterns, were examined. The Cox proportional hazards regression model was used to examine the relationships between dietary patterns and incidence of fall-related fracture with adjustment for age, gender, Body Mass Index (BMI) and energy intake. RESULTS: Among 877 participants who agreed to a 4 year follow-up, 28 suffered from a fall-related fracture. Three dietary patterns were identified: mainly vegetable, mainly meat and mainly traditional Japanese. The moderately confirmed (see statistical methods) groups with a Meat pattern showed a reduced risk of fall-related fracture (Hazard ratio = 0.36, 95% CI = 0.13 - 0.94) after adjustment for age, gender, BMI and energy intake. The Vegetable pattern showed a significant risk increase (Hazard ratio = 2.67, 95% CI = 1.03 - 6.90) after adjustment for age, gender and BMI. The Traditional Japanese pattern had no relationship to the risk of fall-related fracture. CONCLUSIONS: The results of this study have the potential to reduce fall-related fracture risk in elderly Japanese. The results should be interpreted in light of the overall low meat intake of the Japanese population.

Calcium intake and the risk of osteoporosis and fractures in French women.

OBJECTIVES: To evaluate dietary calcium intake in postmenopausal women over 45 years of age and compare intake according to osteoporosis diagnosis and fracture history. METHODS: A cross-sectional epidemiological survey of osteoporosis in postmenopausal women over 45 years in the general population was conducted using a stratified random sampling method and face-to-face interviews. Information was collected on osteoporosis diagnosis, fracture history and risk factors. Information on dietary calcium intake was collected using a validated questionnaire. RESULTS: Two thousand six hundred and thirty-one women (mean age: 67.9+/-10.0 years) were included. Two hundred and fifty-four (9.7%) had received a diagnosis of osteoporosis by bone densitometry, of whom 154 (45.3%) reported at least one previous fracture. Total mean daily dietary calcium intake was 754 mg/day, of which dairy products (milk, cheese and others) were the principal source. Overall, 37.2% of the sample consumed<600 mg/day and 20.1% >1000 mg/d. The proportion of women consuming <600 mg/day increased with age (p=0.0028). No difference in mean daily calcium intake was observed between women with or without a diagnosis of osteoporosis or with or without fractures. CONCLUSIONS: Mean dietary calcium intake in this population is well below that recommended in current national guidelines (> or =1500 mg/day), notably in those most at risk for fractures, such as women with a diagnosis of osteoporosis or those in older age groups. Intake does not appear to be influenced by osteoporosis diagnosis or fracture experience.

Strategies to reverse bone loss in women with functional hypothalamic amenorrhea: a systematic review of the literature.

UNLABELLED: Functional hypothalamic amenorrhea (FHA) impairs the attainment of peak bone mass and as such can increase the risk of fractures later in life. To document available treatment strategies, we conducted a systematic review of the literature. We report that hormonal therapies have limited effectiveness in increasing bone mass, whereas increased caloric intake resulting in weight gain and/or resumption of menses is an essential strategy for restoring bone mass in women with FHA. INTRODUCTION: Women with functional hypothalamic amenorrhea (FHA) may not achieve peak bone mass (PBM), which increases the risk of stress fractures, and may increase the risk of osteoporotic fractures in later life. METHODS: To identify effective treatment strategies for women with FHA, we conducted a systematic review of the literature. We included randomized controlled trials (RCTs), cross-sectional studies, and case studies that reported on the effects of pharmacological and non-pharmacological interventions on bone mineral density (BMD) or bone turnover in women with FHA. RESULTS: Most published studies (n=26) were designed to treat the hormonal abnormalities observed in women with FHA (such as low estrogen, leptin, insulin-like growth factor-1, and DHEA); however none of these treatments demonstrated consistent improvements in BMD. Therapies containing an estrogen given for 8-24 months resulted in variable improvements (1.0-19.0%) in BMD, but failed to restore bone mass to that of age-matched controls. Three studies reported on the use of bisphosphonates (3-12 months) in anorexic women, which appear to have limited effectiveness to improve BMD compared to nutritional treatments. Another three investigations showed no improvements in BMD after androgen therapy (DHEA and testosterone) in anorexic women. In contrast, reports (n=9) describing an increase in caloric intake that results in weight gain and/or the resumption of menses reported a 1.1-16.9% increase in BMD concomitant with an improvement in bone formation and reduction in bone resorption markers. CONCLUSIONS: Our literature review indicates that the most successful, and indeed essential strategy for improving BMD in women with FHA is to increase caloric intake such that body mass is increased and there is a resumption of menses. Further long-term studies to determine the persistence of this effect and to determine the effects of this and other strategies on fracture risk are needed.

Clinical management and algorithms in osteoporosis.

The aim of management in osteoporosis is to reduce the risk of fractures. Case-finding strategies are currently recommended to identify subjects at high risk of future fracture who will benefit most from therapy. This article reviews these approaches and discusses the current and future treatment options that are available for patients with osteoporosis.

Dietary calcium and vitamin D intake in relation to osteoporotic fracture risk.

The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain, despite considerable research efforts. With the aim to examine these associations with an improved precision, we used data from a large population-based prospective cohort study in central Sweden. We estimated nutrient intake from a self-administered food-frequency questionnaire filled in by 60,689 women, aged 40-74 years at baseline during 1987-1990. During follow-up, we observed 3986 women with a fracture at any site and 1535 with a hip fracture. Rate ratio of fractures (RR) and 95% CI were estimated using Cox proportional hazards models. We found no dose-response association between dietary calcium intake and fracture risk. The age-adjusted RR of hip fracture was 1.01 (95% CI 0.96-1.06) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 (95% CI 0.96-1.03). Furthermore, women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes: RR 1.07 (95% CI 0.92-1.24) and RR 1.00 (95% CI 0.79-1.27), respectively. Vitamin D intake was not associated with fracture risk. Furthermore, women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures (95% CI 0.88-1.17). Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women.

Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia.

OBJECTIVE: To evaluate fracture rate and bone mineral density (BMD) and body composition in children with acute lymphoblastic leukemia (ALL) treated with dexamethasone-based chemotherapy. STUDY DESIGN: Children with ALL (n = 61) participated. At diagnosis, during therapy, and one year after cessation of therapy, BMD and body composition were measured using dual energy X-ray absorptiometry of lumbar spine (LS) and total body (TB). Serum markers of bone turnover were assessed. RESULTS: BMD(LS) was significantly reduced at diagnosis, and remained low during therapy. BMD(TB) was normal at diagnosis, with a fast decrease in the first 32 weeks, in which chemotherapy was relatively intensive. Apparent ("volumetric") BMD(LS) was also reduced, but this did not reach significance at diagnosis and follow-up. Bone formation markers were reduced at diagnosis; formation as well as resorption markers increased during treatment. Fracture rate was 6 times higher in ALL patients compared with healthy controls. Lean body mass was decreased at baseline. Percentage of body fat increased significantly during therapy. After ALL treatment was completed, BMD and body composition tended to improve. CONCLUSIONS: Children with ALL are at risk for osteopenia because of the disease itself and the intensive chemotherapy. Fracture rate increases substantially, not only during but also shortly after treatment.

The effect of protein malnutrition and nutritional support on the mechanical properties of fracture healing in the injured rat.

We investigated the effect of different nutritional regimens on fracture healing in the injured rat model. Four groups, each consisting of 12 male rats (307 +/- 16 g), were subjected to anesthesia, laparotomy (injury), and tibial osteotomy with internal fixation. Group I received 23% protein, group II received 23% protein and high caloric feed, group III received 5% protein, and group IV received 38% protein. After 8 weeks, calluses were x-rayed and the tibia was removed, fixed in a special block of methyl-metacrylate, and tested at tension up to failure in a mechanical testing apparatus. The distraction force at failure was measured, and callus stiffness and energy absorbed to failure were calculated. The low protein diet resulted in significantly lower tensile strength and stiffness of calluses compared to the other three dietary regimens, this despite adequate caloric intake. In addition, the low protein diet resulted in a callus with "rubbery" mechanical properties compared to the "rigid" calluses of the other three groups. The high protein diet did not result in any significant improvement in fracture healing. These results gain clinical significance in the face of a high incidence of protein calorie malnutrition in injured orthopedic surgery patients.