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Vitamin D and bone health: Is there a need to review supplementation in osteoporosis risk population?
Abstract
Vitamin D is an essential hormone for achieving an optimal bone physiology. There is no universal consensus nowadays on the definition of hypovitaminosis D and cut-off values have been refined in the last years. The aim of this review is to analyze vitamin D deficiency among osteoporosis risk populations, including elderly and postmenopausal women, in Spain and other countries. We also review vitamin D supplementation: current clinical guidelines, last clinical studies, safety, and prescription schemes.
... Pese a que sería de esperar que la población que vive en los países del sur de Europa, como es el caso de España, presentara una situación adecuada de la vitamina dada la mayor exposición solar en comparación con los países situados al norte del continente, se observa una prevalencia elevada de deficiencia de la vitamina en diferentes colectivos 19 , lo que puede ser debido a una serie de factores que reducen la síntesis de la vitamina D en el organismo, especialmente en invierno y a una ingesta insuficiente 15,20 . ...
VITAMIN D STATUS AND STRATEGIES TO MEET THE DIETARY REFERENCE INTAKES
Abstract
Vitamin D is an essential nutrient for the organism and in the recent years its importance has risen because,
besides its role in the metabolism of calcium and phosphorus, also it has been related to the prevention and
control of various chronic diseases, such as cardiovascular disease, diabetes, some types of cancer and osteoporosis. The main source of the vitamin is cutaneous synthesis through sun exposure of the skin. However, there are different biological and environmental factors, such as age, race, use of sunscreen, type of clothes worn, etc., that may determine its production. Therefore, the contribution from foods that naturally contain the vitamin, fortified foods and dietary supplements, acquires a fundamental role in order to meet the dietary reference intakes in the population and maintain the optimal vitamin status. Several studies highlight the problem of deficiency in different groups of the Spanish population, due to inadequate cutaneous synthesis and insufficient intake, influenced by a low intake of foods that contain vitamin D and supplements. It is necessary to implement strategies to prevent and control the problem in the population, as promote the consumption of the main food sources of the vitamin, increase the availability of fortified foods, both animal and vegetable origin, and consider the use of supplements, especially in those groups at risk of deficiency such as children and the elderly.
... Several studies have reported a high prevalence of vitamin D deficiency among different groups of the Spanish population (Del Campo et al., 2005; Calatayud et al., 2009; Galan et al., 2011; Rodriguez-Rodriguez et al., 2011). This vitamin D deficiency may be the result of insufficient sun exposure, resulting from the use of sunscreens , the type of clothing worn and the length of exposure to the sun (Ovesen et al., 2003), which reduces the synthesis of vitamin D in the body, especially in winter (Ovesen et al., 2003; Hill et al., 2004). ...
Vitamin D plays an essential role in bone mineralisation and its deficiency is associated with several chronic diseases. Some studies have reported a deficient status of vitamin D in Spanish and European population. The present study aimed to assess vitamin D intake, dietary sources of this nutrient and its adequacy with respect to the dietary reference intakes (DRI) in a representative sample of Spanish adults.
Four hundred and eighteen adults (aged 18–60 years) from 15 Spanish provinces were studied. They constituted a representative sample of the Spanish adult population. Energy and nutrient intake were determined using a 24-h dietary recall questionnaire for two consecutive days. Vitamin D intake was compared with the DRI for this vitamin.
Mean (SD) vitamin D intake was 3.5 (4.0) μg day–1 (69.5% of the DRI). Of the participants studied, 81.6% had vitamin D intakes below the DRI and 68.7% had intakes below 67% of the DRI. Of the vitamin D, 91.4% came from food sources and 8.6% came from dietary supplements. The main food sources of vitamin D were fish, eggs, dairy products, cereals, oils and meat. In addition, those subjects who met the DRI for vitamin D had a higher consumption of fish, vegetables and fruits and a lower consumption of meats than those subjects who did not meet the DRI.
Vitamin D intake was inadequate in the sample of the adult Spanish population. Therefore, an increase in the consumption of oily fish, as well as fortified dairy products and cereals, might help to improve vitamin D intake.
Objective:
To study the prevalence of osteoporosis and fracture probability in patients diagnosed with prostate cancer.
Design:
Observational descriptive transversal study. SITE: Study performed from Primary Care of Lugo in collaboration with Rheumatology and Urology Services of our referral hospital.
Participants:
Patients diagnosed with prostate cancer without bone metastatic disease from January to December 2012.
Main measurements:
Epidemiologic, clinical, laboratory and densitometric variables involved in osteoporosis were collected. The likelihood of fracture was estimated by FRAX(®) Tool.
Results:
Eighty-three patients met the inclusion criteria. None was excluded. The average age was 67 years. The Body Mass Index was 28.28. Twenty-five patients (30.1%) had previous osteoporotic fractures. Other prevalent risk factors were alcohol (26.5%) and smoking (22.9%). Eighty-two subjects had vitamin D below normal level (98.80%). Femoral Neck densitometry showed that 8.9% had osteoporosis and 54% osteopenia. The average fracture risk in this population, estimated by FRAX(®), was 2.63% for hip fracture and 5.28% for major fracture. Cut level for FRAX(®) major fracture value without DXA >5% and ≥7.5% proposed by Azagra et al. showed 24 patients (28.92%) and 8 patients (9.64%) respectively.
Conclusions:
The prevalence of osteoporosis in this population was very high. The more frequent risk factors associated with osteoporosis were: previous osteoporotic fracture, alcohol consumption, smoking and family history of previous fracture. The probability of fracture using femoral neck FRAX(®) tool was low. Vitamin D deficiency was very common (98.8%).
Introduction
Vitamin D deficiency is common in the elderly, especially among institutionalized and/or hip fracture patients. However, there are few population studies on the prevalence of this deficiency in the general population over 64 years in our environment. The aim of this study was to determine the prevalence of vitamin D deficiency in an urban population cohort of over 64 years, and analyze its relationship with sociodemographic, climatic, and health factors.
Material and methods
Cross-sectional study from «Peñagrande cohort», a population-based cohort consisting of people over 64 years. We determined 25-hydroxyvitamin D levels, and recorded sociodemographic data (age, sex, marital status, education, socioeconomic status), season of measurement and health variables (comorbidity, obesity, malnutrition, renal failure, cognitive impairment, vitamin D supplements, and disability).
Results
A total of 468 individuals with a mean age of 76.0 years (SD: 7.7) were included, of which 53.4% were women. The mean value of vitamin D was 20.3 ± 11.7 ng/mL. The large majority (86.3%, 95% CI: 83.0-89.5) had a vitamin insufficiency (≤ 30 ng/ml), and 35.2% (95% CI: 30.8-39.7) showed severe vitamin deficiency (≤ 15 ng/ml). Vitamin insufficiency increases linearly with age (OR 1.06; 95% CI: 1.01-1.11), and was associated with low socioeconomic status (OR 3.29; 95% CI: 1.55-6.95). Severe vitamin D deficiency increases with age (OR 1.06; 95% CI: 1.02-1.09), female gender (OR 1.80; 95% CI: 1.18-2.75) and with cognitive impairment (OR 1.71; 95% CI: 1.04-2.83).
Conclusion
The prevalence of vitamin D deficiency in people over 65 years of age in our community is high. It would be advisable to determine the vitamin D values in the high risk elderly in order to introduce measures of pharmacological supplementation in those with inadequate levels.
This study aims to evaluate the prevalence of vitamin D deficiency and insufficiency in older subjects. A cross-sectional population study in subjects over 65 years of age residing in their home, in a nursing home and in-patients was performed. A total of 454 persons were evaluated. Mean serum concentrations of 25 (OH) D3 were 37± 20 nmol/l in home subjects, 33±17 nmol/l in nursing home and 27±14 nmol/l in in-patients. An inverse correlation between paratohormon (PTH) and vitamin D was found (r: -0.257, p = 0.0001). Vitamin D deficiency and insufficiency were present in 79% and 31% in home subjects, 91% and 32% in nursing home and 92% and 52% in in-patients. In conclusion, hypovitaminosis D is a very frequent finding in elderly people of the population of our health care area.
Correspondencia: Dra. Ana Romagosa Pérez-Portabella. Centro de Salud Dr. Sayé. Torres i Amat, 8. 08001 Barcelona. España.
Introduction
Osteoporosis is a chronic disease that affects more than two million women in Spain. In addition to an antiresorptive agent in its therapeutic approach, adequate intake of calcium and vitamin D should be assured. When the patient cannot achieve these minimum daily requirements, these should be administered exogenously through supplements. The real situation in regard to the prescription and degree of compliance with these elements from the clinical practice of Primary Care is unknown, thus we have considered conducting a pragmatic study to address the unanswered questions.
Methods
Cross-sectional study which includes an ad hoc questionnaire, based on the study objective that was administered by 49 Primary Care physicians from the 32 health districts of Andalusia, during March-April 2006, who were chosen by non-probability sampling criteria, the condition of being an expert in osteoporosis being the selection criteria. Each one of the investigators had to contact at least 10 Primary Care physicians in the Primary Care area providing them with the questionnaire.
Results
A total of 749 Primary Care physicians from all of the health districts answered the questionnaire. Information was collected from 3,745 patients since each physician had to review 5 clinical records of patients being treated for osteoporosis. A total of 31% of the physicians admitted that they were not concomitantly associating an antiresorptive agent with calcium-vitamin D supplements for at least 50% of the time. Fifty-two percent of those questioned admitted that tolerance to calcium supplements is either regular, poor or very poor, and up to 62% of the physicians addressed claimed that 50% of their patients discontinued supplement treatment within a three month period due to intolerance or adverse effects. Fifty percent of the physicians admitted they were not concerned about vitamin D intake in these patients, since they believed that due to the sunny climate in Spain, insufficient vitamin D was not a frequent issue.
Conclusions
The majority of Primary Care physicians in Andalusia believe that compliance with calcium and vitamin D supplements for concomitant treatment of osteoporosis is quite poor. Therefore, integral therapeutic management of osteoporosis is inadequate. An effort must be made to increase physicians’ awareness regarding adequate intake of calcium and vitamin D. There is a high rate of withdrawal of supplements due to side effects or intolerance as well as a false concept of association between sun exposure and adequate vitamin D levels.
Background and objective
Supplements of calcium and vitamin D (Ca/VitD) could help prevent falls, although it is unknown whether the effect differs according to the level of physical activity or baseline 25-OH-vitamin D3. The objective is to determine the effect of Ca/VitD supplements in reducing falls and the musculoskeletal function in elderly over 65 years living in the community, who do not have osteoporosis or vitamin D deficiency.
Material and method
Randomized double-blinded clinical trial. A total of 508 patients were selected from 35 Family Medicine consultations. The treatment was administered to 398 subjects (Ca/VitD 188 and placebo 210). The efficacy parameters were: incidence of falls, changes in muscle strength in dominant hand and changes in musculoskeletal function.
Results
The cumulative incidence of falls in the group Ca/VitD was 27.7% (95% confidence interval [95% CI]: 21.0 to 34.3) and 30.5% in the placebo group (95% CI: 24.0 to 36.9) (P = .537). The difference was not significant in the subgroup analysis: male/female, active/inactive physically and level of 25-OH-vitamin D3 higher/less than 32 ng/ml. There was no difference in muscle strength in subjects of both groups. The proportion of adverse effects was higher in the Ca/VitD group (14.4 versus 7.1%, P = .019).
Conclusions
The results contradict the recommendation to provide supplements, and it is not an effective and well tolerated strategy. Although they may reduce the risk of falls when there are very low levels of vitamin D, the results are unsatisfactory when elders do not have this deficiency, and it is necessary to consider the possibility of adverse effects.
BACKGROUND AND OBJECTIVE: Supplements of calcium and vitamin D (Ca/VitD) could help prevent falls, although it is unknown whether the effect differs according to the level of physical activity or baseline 25-OH-vitamin D(3). The objective is to determine the effect of Ca/VitD supplements in reducing falls and the musculoskeletal function in elderly over 65 years living in the community, who do not have osteoporosis or vitamin D deficiency. MATERIAL AND METHOD: Randomized double-blinded clinical trial. A total of 508 patients were selected from 35 Family Medicine consultations. The treatment was administered to 398 subjects (Ca/VitD 188 and placebo 210). The efficacy parameters were: incidence of falls, changes in muscle strength in dominant hand and changes in musculoskeletal function. RESULTS: The cumulative incidence of falls in the group Ca/VitD was 27.7% (95% confidence interval [95% CI]: 21.0 to 34.3) and 30.5% in the placebo group (95% CI: 24.0 to 36.9) (P=.537). The difference was not significant in the subgroup analysis: male/female, active/inactive physically and level of 25-OH-vitamin D(3) higher/less than 32ng/ml. There was no difference in muscle strength in subjects of both groups. The proportion of adverse effects was higher in the Ca/VitD group (14.4 versus 7.1%, P=.019). CONCLUSIONS: The results contradict the recommendation to provide supplements, and it is not an effective and well tolerated strategy. Although they may reduce the risk of falls when there are very low levels of vitamin D, the results are unsatisfactory when elders do not have this deficiency, and it is necessary to consider the possibility of adverse effects.
There are many studies that associate vitamin D serum levels in older persons with muscle strength, physical performance and risk of fractures and falls. However, current evidence is insufficient to make a general recommendation for administrating calcium and vitamin D to older persons. The objective of this study is to determine the effectiveness of calcium and vitamin D supplementation in improving musculoskeletal function and decreasing the number of falls in person aged over 65 years.
Phase III, randomized, double blind, placebo-controlled trial to evaluate the efficacy of already marketed drugs in a new indication. It will be performed at Primary Care doctor visits at several Healthcare Centers in different Spanish Health Areas. A total of 704 non-institutionalized subjects aged 65 years or older will be studied (sample size calculated for a statistical power of 80%, alpha error 0.05, annual incidence of falls 30% and expected reduction of 30% to 20% and expected loss to follow up of 20%). The test drug containing 800 IU of vitamin D and 1000 mg of calcium will be administered daily. The control group will receive a placebo. The subjects will be followed up over two years. The primary variable will be the incidence of spontaneous falls. The secondary variables will include: consequences of the falls (fractures, need for hospitalization), change in calcidiol plasma levels and other analytical determinations (transaminases, PTH, calcium/phosphorous, albumin, creatinine, etc.), change in bone mass by densitometry, change in muscle strength in the dominant hand and change in musculoskeletal strength, risk factors for falls, treatment compliance, adverse effects and socio-demographic data.
The following principles have been considered in the development of this Project: the product data are sufficient to ensure that the risks assumed by the study participants are acceptable, the study objectives will probably provide further knowledge on the problem studied and the available information justifies the performance of the study and its possible risk for the participants.If calcium and vitamin D supplementation is effective in the prevention of falls and fractures in the elderly population, a recommendation may be issued with the aim of preventing some of the consequences of falls that affect quality of life and the ensuing personal, health and social costs.
ClinicalTrials.gov: NCT01452243
To determine the level of hypovitaminosis D in adult healthy women attended in primary care and their associated factors.
Cross-sectional, descriptive study.
A neighbourhood of Barcelona, Spain, with a socially deprived population with a high percentage of immigrants, and urban factors which meant that they lived with hardly any sunlight.
Women between 15-50 years seen between February and March 2005.
Primary: residence time (years), skin phototype, sun exposure, vitamin D deficiency pain type, calcium, vitamin D consumed, and measurement of serum 25-hydroxyvitamin D (25[OH]D) or calcidiol and parathyroid hormone (PTH) if (25[OH]D) was <10 ng/mL; 94 women were included. Mean age: 33 years (SD, 7.8); 62.8% immigrants (mean years of residence, 11.5). Mean (25[OH]D), 14.0 ng/mL (95% CI, 12.5-15.5). Skin phototype V-VI was associated with low levels of (25[OH]D) (P=.001). None of the women stated that they consumed the recommended amount of vitamin D and only 46% the recommended amount of calcium. Sun exposure of >4 hours/week: 37%. Sixteen percent had musculo-skeletal pain. No relationship was found between vitamin D levels and immigration. All the women had (25[OH]D) levels of <40 mg/mL, 47.9% had insufficient (25[OH]D), 10-20 ng/mL, and 37.2% were deficient: pound10 mg/mL. PTH was within the normal range.
All the women had low levels of vitamin D, more than a third of these, deficient. No relationship with immigration was found. A relationship was established between skin phototype V-VI and (25[OH]D) deficiency. None of the cases consumed the recommended amounts of vitamin D.
In an effort to reduce the complications of Scopinaro's biliopancreatic diversion (BPD), in 1989 we introduced the modification of lengthening the alimentary channel preserving most of the jejunum-ileum, by creating a short biliopancreatic limb (50 cm) and maintaining 50 cm of common limb (Larrad 50-50 BPD).
Of 343 patients who consecutively underwent Larrad 50-50 BPD surgery, 325, 194 and 65 patients were evaluated at 2, 5 and 10 years after surgery, respectively, in terms of surgical morbidity, mortality, metabolic sequelae and weight. Mean age was 41.2 years (range 17-62), mean initial weight 151.2 kg (range 97-260), and BMI was 52.2 kg/m2. Maximum follow-up was 120 months.
Mortality was 0.87% and surgical morbidity 7.6%. There were no cases of suture dehiscence, peritonitis or stomal stenosis. Percent excess weight loss (%EWL) stabilized 2 years after surgery and at 10 years was 77.8 +/- 11.2% for morbidly obese patients and 63.2 +/- 11.8% for super-obese patients. The main complications were 43.8% clinical incisional hernia, 2.5% severe diarrhea, 10.8% mild diarrhea and 9.2% constipation. 30% experienced anemia and/or iron deficiency, and 3% required iron parenterally or lifelong zinc supplements. 28% showed preoperative PTH elevation and 30% vitamin D deficiency; these values postoperatively increased to 45% and 43% respectively. Both these alterations were resolved using supplements, although 12% needed increased doses of vitamin D. The incidence of severe hypoproteinemia was 0.29%. No patient required surgical reversal. When independently evaluated, failure rates in terms of insufficient weight loss were 9% at 5 years and 11.3% at 10 years for morbidly obese, and 12.2% and 14% for super-obese patients respectively. According to the BAROS questionnaire, 75% of surgery outcomes were excellent or very good, 18% good, 5% fair and 2% failures.
After 2, 5 and 10 years, Larrad's BPD has offered excellent results in terms of weight loss and quality of life, a low rate of metabolic sequelae, including a hypoproteinemia rate < 0.5%, and a revision surgery rate 0%.
Objective: To review the effect of vitamin D on bone density and fractures in postmenopausal women. Data Source: We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data. Study Selection: We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr. Data Extraction: For each trial, three independent reviewers assessed the methodological quality and abstracted data. Data Synthesis: Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 μg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D. Conclusions: Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.
Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown.
We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward.
A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent.
Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.
Our data show clearly that low plasma 25-OHD concentrations are more common in patients suffering a fracture of the femoral neck than in matched controls. The figure of 40% with 25-OHD concentrations below 25 nmol/l (10 ng/ml), the level below which most cases of histological osteomalacia occur, is consistent with the 30% prevalence of histological osteomalacia reported, since not all patients with vitamin D deficiency develop osteomalacia. Low dietary vitamin D and lack of sunlight both contribute to this deficiency but the latter is clearly the more important factor. The patients with fractures, 51% of whom were housebound, depended for their vitamin D supply on their diet, which was inadequate. The controls, being more active, obtained their vitamin D from sunlight, which is why their plasma concentrations were relatively independent of their vitamin D intake. We suggest that vitamin D deficiency contributes to the high incidence of fractures of the neck of the femur in Britain through an effect on the skeleton or on muscle power, or both. If this is so the rate of fractures to the femoral neck might be substantially reduced by improving the vitamin D status of the elderly population.
The factors that influence vitamin D status were investigated in 125 patients with hip fracture and in 74 elderly control subjects. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] varied with sunshine score and were paralleled by serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The control subjects showed a higher sunshine score and higher serum 24(OH)D levels than the patients with hip fracture. Dietary vitamin D intake was similar in both groups (mean 115 IU/d). A positive correlation between vitamin D intake and serum 25(OH)D was observed in the patients with low sunshine exposure. It appeared from this relation that dietary vitamin D intake should be approximately 300 IU/d to maintain an adequate serum (25(OH)D concentration. Vitamin D status was very poor in patients who were institutionalized before hip fracture. Multiple regression analysis on serum 25(OH)D confirmed the primary role of sunshine exposure as determinant of vitamin D status. The principal determinants of serum 1,25(OH)2D were serum 25(OH)D, serum creatinine, and serum phosphate.
Problems of compliance and malabsorption in the elderly led us to examine the effect of a single depot injection of vitamin D in seven elderly women with osteomalacia. We found that a single 15 mg injection of vitamin D was effective in initiating and sustaining healing of osteomalacia for at least six months. Our regimen is safe: no patient developed hypercalcaemia, and concentrations of 25-hydroxy-vitamin D remained well below values seen in poisoning with vitamin D. Vitamin D given intramuscularly probably remains at the site of injection and is released slowly into the blood.
To determine whether vitamin D supplementation decreases the incidence of hip fractures and other peripheral bone fractures.
Prospective, double-blind trial.
Community setting (Amsterdam and surrounding area).
2578 persons (1916 women, 662 men) 70 years of age and older (mean age +/- SD, 80 +/- 6 years) living independently, in apartments for elderly persons, or in homes for elderly persons.
Participants were randomly assigned to receive either vitamin D3, 400 IU in one tablet daily, or placebo for a maximum of 3.5 years.
Dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] were estimated in a subset of participants. During follow-up, attention was concentrated on hip fractures and other peripheral fractures. The maximal follow-up period was 4 years. The results were evaluated by survival analysis.
Mean dietary calcium intake from dairy products was 868 mg/d. Mean serum 25(OH)D concentration in the third year of the study was 23 nmol/L in the placebo group and 60 nmol/L in the vitamin D group. Median follow-up was 3.5 years, and total follow-up was 8450 patient-years. During follow-up, 306 persons in the placebo group and 282 persons in the vitamin D group died (P = 0.20). Hip fractures occurred in 48 persons in the placebo group and 58 persons in the vitamin D group (P = 0.39, intention-to-treat analysis). Other peripheral fractures occurred in 74 persons in the placebo group and 77 persons in the vitamin D group (P = 0.86).
Our results do not show a decrease in the incidence of hip fractures and other peripheral fractures in Dutch elderly persons after vitamin D supplementation.
Low vitamin D levels may contribute to hip fractures in women, although limited data are available on vitamin D levels in US women admitted with acute hip fractures.
To determine whether postmenopausal women with hip fractures have low vitamin D and high parathyroid hormone levels compared with nonosteoporotic and osteoporotic women admitted for elective joint replacement.
Comparative case series conducted between January 1995 and June 1998.
Ninety-eight postmenopausal community-dwelling women with no secondary causes of bone loss admitted for hip replacement, of whom 30 women had acute hip fractures and 68 women were admitted for elective joint replacement. Of the women admitted for elective joint replacement, 17 had osteoporosis and 51 did not. Women with comorbid conditions or who were taking medications that affect bone density and turnover were excluded.
Primary measures were levels of vitamin D and parathyroid hormone; secondary measures were body composition and markers of bone turnover.
Women with hip fractures had lower levels of 25-hydroxyvitamin D than women without osteoporosis admitted for elective joint replacement (P = .02) and than women with osteoporosis admitted for elective joint replacement (P = .01) (medians, 32.4, 49.9, and 55.0 nmol/L, respectively; comparisons adjusted for age and estrogen intake). Parathyroid hormone levels were higher in women with fractures than women in the nonosteoporotic control group (P<.001) or than elective osteoporotic women (P = .001) (medians, 5.58, 3.26, and 3.79 pmol/L, respectively; comparisons adjusted for age and estrogen intake). Fifteen patients (50.0%) with hip fractures had deficient vitamin D levels (< or =30.0 nmol/L) and 11 (36.7%) had a parathyroid hormone level greater than 6.84 pmol/L. Levels of N-telopeptide, a marker of bone resorption, were greater in the women with hip fractures than in the elective nonosteoporotic controls (P = .004).
Postmenopausal community-living women who presented with hip fracture showed occult vitamin D deficiency. Repletion of vitamin D and suppression of parathyroid hormone at the time of fracture may reduce future fracture risk and facilitate hip fracture repair. Because vitamin D deficiency is preventable, heightened awareness is necessary to ensure adequate vitamin D nutrition, particularly in northern latitudes.
To establish the prevalence of hypovitaminosis D among free-living postmenopausal women referred to an osteoporosis outpatient clinic in Northern Italy, we evaluated 25-hydroxyvitamin D (25(OH)D) levels in 570 postmenopausal women who had been consecutively referred to our clinic in the 12 months beginning October 1995. Parathyroid hormone (PTH), serum calcium (Ca), creatinine (Cr) and osteocalcin (OC), urinary calcium (Ca24h) and creatinine (Cr24h), and the bone mineral density of the lumbar spine (LBMD) and femur (FBMD) were also measured. 1,25-Dihydroxyvitamin D (1,25(OH)2D) concentrations were measured in 23 women. All women had normal electrolyte serum concentrations and kidney function. Mean +/- SD 25(OH)D concentration was 18.3 +/- 8.3 ng/ml. A significant (p < 0.001) seasonal variation was seen for both 25(OH)D and PTH. Women were divided into two groups based on their vitamin D status: low vitamin D status (25(OH)D < 12 ng/ml, n = 161, 28%) and normal vitamin D status (25(OH)D > or = 12 ng/ml, n = 409, 72%). Hypovitaminosis D was found in 38.5% of all the women in the time period December-May and in 12.5% in the other half-year; among women > 70 years old 51% had hypovitaminosis D in the time period December-May and 17% in the other half-year. PTH was significantly (p < 0.05) increased, and Ca24h, OC and FBMD significantly (p < 0.05) decreased in women with hypovitaminosis D. 1,25(OH)2D positively correlated with 25(OH)D (p < 0.0001), but did not correlate with PTH, age or creatinine clearance. In conclusion, hypovitaminosis D is an important, underestimated problem in Italian free-living postmenopausal women referred to an outpatient osteoporosis clinic.
The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level (LOAEL).
Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg (1000 and 4000 IU)/d. Efficacy was based on the lowest serum 25-hydroxyvitamin D [25(OH)D] concentration achieved by subjects taking vitamin D3; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios.
Healthy men and women (n = 61) aged 41 +/- 9 y (mean +/- SD) were randomly assigned to receive either 25 or 100 microg vitamin D3/d for 2-5 mo, starting between January and February. Serum 25(OH)D was measured by radioimmunoassay.
Baseline serum 25(OH)D was 40.7 +/- 15.4 nmol/L (mean +/- SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 +/- 16.9 nmol/L in the 25-microg/d group and at 96.4 +/- 14.6 nmol/L in the 100-microg/d group. Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 +/- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively. Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study.
The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 microg vitamin D3/d to be a safe intake.
A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liège, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits; (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures; (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy; (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis; (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk; and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products.
Background
Vitamin D deficiency has been frequently observed in the elderly population in Europe.However few information is available about the vitamin D status in postmenopausal womenin the Mediterranean countries. The aim of this study was to evaluate the vitamin D statusassessed by serum 25(OH)D3 (calcidiol) in postmenopausal women who attended a Rheumatologypractice in Madrid area, and to evaluate calcidiol serum levels through one year after twoforms of vitamin D administration.
Patients and Methods
Calcidiol serum levels were measured in 171 postmenopausal women(111 with osteoporosis and 60 without osteoporosis). 82 women with calcidiol serum levels < 10 ng/ml were distributed in two groups: Group I received 800 U/day of vitamin D3 associatedwith calcium (1 g/day) and group II, one dose of 80.000 U vitamin D orally as calcidiol and lattera daily dose of 800 U vitamin D3 plus 1 g calcium. Calcidiol serum levels were measured byRIA in both groups at basal condition and after three, six and twelve months under treatment.
Results
Three cut-offs were considered: 10, 15 and 20 ng/ml of calcidiol. Percentages of postmenopausalwomen with vitamin D deficiency for such cut-offs were: 35.3%, 64.1% and87.1%, respectively. After three months of treatment, women from group II showed calcidiolserum levels higher than group I. At six and twelve months calcidiol serum levels were similarin both groups.
Conclusions
A high prevalence of vitamin D deficiency was observed in a group of postmenopausalwomen who attended a rheumatology practice in Madrid area. Both forms of vitamin Dadministration seem not sufficient to maintain the adequate calcidiol serum levels in postmenopausaldeficient women. A dose of 80.000 U of calcidiol twice a year should be considered.
Although only few postmenopausal women exhibit biochemical signs of hypovitaminosis D, vitamin D insufficiency has been shown to have adverse effects on bone metabolism and could be an important risk factor for osteoporosis and fracture. We determined serum levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), bone turnover markers, dietary calcium intake, and bone mineral density (BMD; measured by dual X-ray absorptiometry) in 161 consecutive ambulatory women, healthy except for osteoporosis, referred to a bone metabolic unit. The prevalence of vitamin D insufficiency [25(OH)D ≤ 15 ng/ml] was 39.1%. 25(OH)D was lower in the osteoporotic subjects (15.7 ± 5.3 ng/ml vs. 21.8 ± 9.7 ng/ml; p < 0.001). After controlling for all other variables, lumbar spine (LS) BMD was found to be significantly associated with 25(OH)D, body mass index (BMI), and years after menopause (YSM) (R2 = 0.253; p < 0.001). For femoral neck (FN), significant independent predictors of BMD were YSM, BMI, iPTH, and 25(OH)D (R2 = 0.368; p < 0.001). The probability of meeting osteoporosis densitometric criteria was higher in the vitamin D insufficiency group (odds ratio [OR], 4.17, 1.83-9.48) after adjusting by YSM, BMI, iPTH, and dietary calcium intake. Our study shows that vitamin D insufficiency in an otherwise healthy postmenopausal population is a common risk factor for osteoporosis associated with increased bone remodeling and low bone mass.
The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7 +/- 15.9 vs 46.0 +/- 27.8 nmol/l) and calcitriol (63.6 +/- 25.0 vs 91.1 +/- 39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (4.7 +/- 2.1 vs 5.3 +/- 3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture.
Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.
We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.
Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001).
Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.
To compare vitamin D status between countries in young adults and in the elderly.
Reports on vitamin D status (as assessed by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kingdom).
Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavia. Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations.
The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the essential means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. All countries should adopt a fortification policy. It seems likely that the elderly would benefit additionally from a daily supplement of 10 micrograms of vitamin D.
To examine the relation between bone density and indices of calcium metabolism including parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women.
A cross sectional study.
138 women volunteers aged 45-65 with no known osteoporosis and unselected for disease status recruited for a dietary assessment study from the community using general practice registers. Volunteer rate was 20%.
Bone mineral density measured with dual energy x ray absorptiometry.
Bone density at the lumbar spine and neck and trochanteric regions of the femur was inversely related to serum intact parathyroid hormone concentrations and positively related to serum 25-hydroxyvitamin D concentrations. These associations were independent of possible confounding factors, including age, body mass index, cigarette smoking habit, menopausal status, and use of diuretics and postmenopausal hormone replacement therapy. These associations were apparent throughout the whole distribution of bone density and 25-hydroxyvitamin D and parathyroid hormone concentrations within the normal range, suggesting a physiological relation.
The findings are consistent with the hypothesis that parathyroid hormone and 25-hydroxyvitamin D concentrations influence bone density in middle aged women. Findings from this study together with other work suggest that the role of vitamin D in osteoporosis should not be neglected. The associations with parathyroid hormone also indicate plausible biological mechanisms. The roughly 5-10% difference in bone density between top and bottom tertiles of serum 25-hydroxyvitamin D concentrations, though not large in magnitude, may have considerable public health implications in terms of prevention of osteoporosis and its sequelae, fractures.
Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25-hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to greater than 40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r = -0.450, P = 0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P = 0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r = 0.509, P = 0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r = -0.382, P = 0.08). Before menopause, the change in PBMC was positively correlated with OC (r = 0.450, P = 0.03). Postmenopause, the correlation with DBMC slope was negative (r = -0.506, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Serum intact parathyroid hormone (PTH), 25 hydroxyvitamin D(25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), albumin, and ionized calcium were measured in 61 Chinese female patients with hip fracture and 61 control subjects. Hip fracture patients had low albumin, ionized calcium, and 250HD levels. Serum PTH and 1,25(OH)2D values were not different between the two groups. We conclude that although 250HD level in hip fracture patients is low, there is no evidence of secondary hyperparathyroidism, suggesting that the low 250HD levels may be a secondary phenomenon in response to the fracture.
The effect of age and vitamin D status on parathyroid function was studied in 129 healthy subjects between 20 and 89 yr old, with normal serum creatinine (less than 0.11 mmol/L), and living in Cordoba, Spain. Serum calcium and phosphorus as well as 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] decreased, whereas serum alkaline phosphatase increased, with age. Serum PTH also increased significantly with age when measured with either a carboxyl-terminal (cPTH) or an intact [PTH(1-84)] assay. The increase in cPTH, however, exceeded largely the increase in PTH(1-84) (+120% and +30% in subjects above 80 yr vs. young adults, respectively). Serum PTH(1-84) was negatively correlated with serum (ionized) calcium, 25OHD, and insulin-like growth factor I (IGF-I) but not with serum 1,25-(OH)2D. Serum 1,25-(OH)2D decreased with age and was highly correlated with serum 25OHD, cPTH, and IGF-I. In multiple regression analysis 50-60% of the variation of total and free 1,25-(OH)2D could be explained by serum 25OHD, PTH(1-84), and especially IGF-I, suggesting a possible role of decreasing GH and IGF-I concentrations in the mineral homeostasis of the elderly. Calcium infusion (1.5 mg/kg body weight over 10 min) decreased serum PTH(1-84) to below normal concentrations in young adults (nadir 14% of basal concentration), whereas the nadir in elderly subjects with secondary hyperparathyroidism was only 32% of basal concentration. The relative decrease was, however, identical in both age groups when simultaneous changes in ionized calcium were taken into account. Basal serum PTH(1-84) in selected elderly subjects (50 +/- 10 ng/L or 5 +/- 1 pmol/L, n = 10) decreased significantly (2.7 +/- 0.9 pmol/L, P less than 0.01) after 3 iv injections of 1,25-(OH)2D during 1 week without changes in serum (ionized) calcium. The PTH suppressibility after calcium infusion did not further improve. In conclusion: elderly patients with normal serum creatinine had a small (+30%) but significant increase in intact serum PTH concentration but the mean concentration still remained within the normal range. The PTH secretion remained normally suppressible by acute calcium infusion. Treatment with 1,25-(OH)2D decreased basal calcium-PTH setpoint without further additional effects during calcium infusion.
To define the potential role of subclinical vitamin D deficiency in postmenopausal bone loss, we analyzed the levels of circulating 25-hydroxyvitamin D (25OHD) in 539 midwestern caucasian women screened for osteoporosis. Low 25OHD (less than 38 nmol/L) was found in 49 subjects (aged 52-77 yr). Women with low 25OHD had a reduced vertebral bone density (VBD), assessed by quantitative computed tomography, compared to age-matched controls (P less than 0.001). They also had significantly lower levels of serum calcium and phosphate, lower urinary calcium, higher serum alkaline phosphatase, and, in most cases, increased immunoreactive PTH (iPTH) concentrations, suggesting secondary hyperparathyroidism. Furthermore, only in the low 25OHD group did VBD correlate directly with 25OHD (r = 0.41; P less than 0.01), and inversely with iPTH (r = -0.47; P less than 0.01). Multivariate analyses revealed that iPTH was the major determinant of the observed decrease in VBD. Seasonal variations of serum 25OHD were noted only in the control population; in this group the 25OHD levels also correlated with sunlight exposure (r = 0.48; P less than 0.01), as assessed by an outdoor score. Thus, vitamin D deficiency develops when both the endogenous and exogenous sources are insufficient and contributes to a reduced bone mass in elderly women.
The effects of age, sex, renal function, and seasonal variation on serum parameters within the vitamin D endocrine system were studied cross-sectionally in a healthy population of 167 men and 114 women, aged 20-94 yr. Serum 25-hydroxy- and 1,25-dihydroxyvitamin D [25OHD and 1,25-(OH)2D] did not decline with age in either sex. Nonlinear regression using a sine function showed a significant seasonal variation in 25OHD and 1,25-(OH)2D in both sexes (P less than 0.005). Serum intact PTH increased significantly by 35% over the age span in both sexes (P less than 0.005). In women, serum phosphorus and total and ionized calcium remained constant with age. In sharp contrast, males had a marked 25% fall in phosphorus across the age span (r = -0.564; P less than 0.0001) and a slight but significant 4% decline in total and ionized calcium. Creatinine clearance declined markedly with age, but was not related to 1,25-(OH)2D in either sex. Only in men was there a significant but modest inverse relationship between creatinine clearance and PTH (r = -0.212; P less than 0.05), which was multicollinear with age. We conclude that in healthy individuals 1) compromised vitamin D status or serum 1,25-(OH)2D levels are not a normal concomitant of aging; 2) declining glomerular filtration does not appear to be the principle cause of the age-related rise in PTH; and 3) there are marked male-female differences in phosphorus metabolism across the age span.
We have assessed indices of calcium metabolism in 41 women with hip fractures and compared them with two elderly control groups. The women with hip fractures had lower serum concentrations of albumin, 25-hydroxyvitamin D and osteocalcin than the controls. Serum concentrations of calcium, alkaline phosphatase and parathyroid hormone, as well as urinary hydroxyproline/creatinine ratios were similar in the three groups of women. The small reduction in serum osteocalcin concentration in fracture patients is consistent with the hypothesis that reduced osteoblast function may contribute to the osteoporosis which results in hip fracture.
A poor vitamin D status is common in the elderly during the winter months. Because it is possible that hypovitaminosis D may be a cause of senile osteopenia, a simple method of prophylaxis would be useful. The single, oral, high-dose method was tested in two old-age homes, and the efficacy of vitamin D3 was compared with that of 25-hydroxyvitamin D3 (25-OHD3). The trials showed that 25-OHD3 caused a higher peak value in the serum 25-OHD levels in the second week than did vitamin D3. However, follow-up after four to five months showed that in those patients who received a single, oral dose of 25-OHD3, the serum 25-OHD levels had returned to the baseline low values, whereas in those patients who had had oral vitamin D3, the serum 25-OHD levels still remained significantly raised compared with the baseline values and were within normal limits. It is concluded that the single, oral, high-dose method using vitamin D3 is a safe and simple method of prophylaxis and could be used easily in large populations of elderly persons.
It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33-94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage form of vitamin D, as well as 25OHD3 (representing both endogenous and exogenous sources of vitamin D), and 25OHD2 (representing only exogenous sources). Both baseline serum total 25OHD (r = -0.29, P less than 0.001) and the metabolite 25OHD3 (r = -0.41, P less than 0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD2, 25OHD3, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age-related bone loss.
Measurements of bone mineral index, mean metacarpal cortical thickness, plasma calcium, alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations were carried out in 39 Asian vegetarian patients with hypovitaminosis D. It was concluded that PTH is probably the major determinant of osteopenia in patients with osteomalacia and secondary hyperparathyroidism; and that the presence of secondary hyperparathyroidism in association with hypovitaminosis D should be an absolute indication for vitamin D supplementation even in asymptomatic patients.
The relationship among serum vitamin D metabolites, PTH, and osteocalcin concentrations was investigated in 20 elderly subjects. All except 2 had subnormal 25-hydroxyvitamin D concentrations. Eighteen (90%) had subnormal serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations, while 8 subjects (40%) had elevated PTH concentrations. There was a highly significant inverse relationship between PTH and 1,25-(OH)2D concentrations. Serum osteocalcin concentrations were not elevated in any subject, and in fact, the mean osteocalcin concentration was in the lower part of the normal range. These data indicate no compensatory increase in 1,25-(OH)2D in response to secondary hyperparathyroidism and no increase in osteocalcin in response to hypersecretion of PTH in the elderly. These 2 defects may contribute to the bone disease of the elderly.
There is uncertainty about the adequacy of renal secretion of 1,25-dihydroxyvitamin D(1,25-(OH)2-D) in elderly patients with osteoporosis. To investigate this uncertainty, we stimulated secretion of 1,25-(OH)2-D with a 24-hour intravenous infusion of synthetic human parathyroid hormone fragment 1-34 and compared the results in normal young adults and elderly patients with untreated osteoporosis. Serum levels of 1,25-(OH)2-D were similar in both groups (49 +/- 10 and 42 +/- 9 pg per milliliter [116 +/- 24 and 99 +/- 21 pmol per liter]) before the infusion. However, during the 24-hour infusion, serum levels nearly doubled (P less than 0.01) in the normal volunteers but did not change significantly in the patients. Serum ionized calcium increased and serum inorganic phosphate decreased similarly in both groups during the infusion (P less than 0.05). Although the present study does not establish whether deficient 1,25-(OH)2-D secretory reserve is an effect of age or of osteoporosis, it is possible that such a deficiency will explain the inability of elderly osteoporotic patients to adapt to the low-calcium diets common in this age group. If so, this phenomenon may play a part in the pathogenesis of age-related osteoporosis.
The effects of age on calciotropic hormones are not completely understood. The presence of secondary hyperparathyroidism has previously been demonstrated, particularly in patients with hip fracture. The role of a disturbance of vitamin D metabolism, especially a defect in 1 alpha-hydroxylation, is debated. The aim of this study was to compare serum parathyroid hormone (PTH), osteocalcin and vitamin D metabolites (25(OH)D and 1,25(OH)2D) in osteoporotic elderly patients with hip fracture (HF) and in elderly controls. We studied 57 HF patients aged 83.9 +/- 5.9 years (mean +/- SD) and 68 controls aged 82.5 +/- 5 years recruited during two periods: 1 January and 30 April 1988 and 1989. Patients with chronic renal failure (serum creatinine above 150 mumol/l), cancer, or other metabolic bone disease were excluded. Thirty healthy young adults were studied in 1989 only for measurement of 1,25(OH)2D. (1,25(OH)2D was measured by different laboratories in 1988 and 1989 for technical reasons.) We also measured serum PTH, osteocalcin, total calcium and ionized calcium. 1,25(OH)2D levels were not statistically different between HF patients and controls for the two years, nor between HF patients and young healthy adults in 1989. 25(OH)D was decreased in HF patients (p < 0.003), as was ionized calcium. Serum PTH levels were higher in HF patients than in controls (p < 0.01). A positive correlation has been found between PTH and age in HF patients (r = 0.29; p < 0.03) and in the whole group of HF patients and controls. There was a significant decrease in osteocalcin in HF patients versus elderly controls (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
The criteria required for an effective screening strategy for osteoporosis are largely met in Caucasian women. The disease is common and readily diagnosed by the measurement of bone mineral with single- or dual-energy absorptiometry. Such measurements have high specificity but lower sensitivity, so that the value of the technique is greater for those identified as being at higher risk. Against this background there is little evidence that osteoporosis can usefully be tackled by a public health policy to influence risk factors such as smoking, exercise and nutrition. This suggests that it is appropriate to consider targetting of treatment with agents affecting bone metabolism to susceptible individuals. Since the main benefits of the use of hormone replacement therapy (HRT) are probably on cardiovascular morbidity, the major role for selective screening is to direct non-HRT interventions. An appropriate time to consider screening and intervention is at the menopause, but screening at later ages is also worthy of consideration. Since the cost of screening is low and that of bone-active drugs is high, the selective use of screening techniques will improve the cost-benefit ratio of intervention.
The relationship between vitamin D and bone density was studied in 150 selected, mature (45-74), postmenopausal women with a lumbar spine Z score below 0. Vitamin D status was evaluated using calcidiol serum levels. Serum calcitriol and parathyroid hormone (PTH) values were also evaluated in some subjects. Bone mass was evaluated by ascertaining bone density and Z and T scores in the lumbar spine and femur region. The reference group consisted of 25 premenopausal women. The postmenopausal group was divided into subgroups according to age, i.e., under or over 60 years old. Additionally, the whole group was also subdivided according to their lumbar spine Z scores into group I (Z > -1), group II (Z < -1; > -2), and group III (Z < -2). Group III of postmenopausal women had higher PTH and lower calcitriol levels than premenopausal women. Calcidiol serum levels were lower in postmenopausal women groups II or III than in the group I and premenopausal women. Calcidiol serum levels and the bone mass values for the lumbar spine were correlated positively in all the postmenopausal women; in the women over 60 years of age, calcidiol levels also correlated with the bone mass values expressed as the bone density in three femur regions: femoral neck, trocanter, and Ward's triangle. In conclusion, mature post-menopausal woman showed high PTH levels and low calcidiol and calcitriol values. Calcidiol status is significantly related to bone mineral density in the lumbar spine and in women over 60 years, calcidiol levels also correlated with bone density in the femur regions.
Vitamin D is absolutely essential for the maintenance of a healthy skeleton throughout our lives. There is mounting evidence that vitamin D insufficiency and vitamin D deficiency in elderly people is a silent epidemic that results in bone loss and fractures. It is casual exposure to sunlight that provides most humans with their vitamin D requirement. Seasonal changes, time of day, latitude, aging, sunscreen use, and melanin pigmentation can substantially influence the cutaneous production of vitamin D. Although the recommended dietary allowance for vitamin D in adults is 5 micrograms (200 IU), there is mounting evidence that in the absence of exposure to sunlight the vitamin D requirement is at least 15 micrograms (600 IU)/d. The skin is a target tissue for the active form of vitamin D (1,25-dihydroxycholecalciferol). 1,25-Dihydroxycholecalciferol inhibits the proliferation of cultured keratinocytes and induces them to differentiate. 1,25-Dihydroxycholecalciferol and its analogs have been developed as an effective new therapy for the treatment of the hyperproliferative skin disease psoriasis.
To the Editor: We reported previously (April 30, 1992, issue)1 that 71 percent of 42 milk samples purchased in five Eastern states in 1991 did not contain 80 to 120 percent of the amount of vitamin D claimed on the label. These results confirmed an earlier study by the Food and Drug Administration (FDA)2. As a result of these observations, there has been increased awareness of the need to monitor the fortification of milk with vitamin D more carefully. Between May 1992 and June 1993, we therefore purchased 94 milk samples in seven Eastern states, including the same five . . .
Vitamin D appears to be implicated in the loss of bone mass and its most severe complication is the hip fracture. A change is produced in the metabolism of vitamin D in elderly people although its study has received little attention in many countries.
With the aim of evaluating vitamin D and its metabolites in the elderly people with hip fracture in our geographic environment (Madrid, Spain), 58 patients with hip fracture over the age of 70, and 39 subjects without a fracture or the similar age were studied. Both groups were evaluated during the season of minimum solar irradiation. The plasma concentrations of intact PTH and the serum concentrations of calcidiol and calcitriol were studied in all the patients.
The patients with hip fracture presented significantly lower concentrations of calcidiol (11.7 +/- 6.4 vs. 18.4 +/- 12.7 nmol/l) and calcitriol (60.1 +/- 24.7 vs. 76.1 +/- 25.0 pmol/l) than in elderly persons without fracture, with similar PTH values being observed in both groups (4.8 +/- 1.9 vs. 5.1 +/- 2.3 pmol/l).
Although Madrid, Spain is considered to be a geographical area of high solar irradiation, the elderly population studied presented a vitamin D deficiency which was found to be greater in those with hip fracture.
Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons.
We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records.
The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02).
In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.
The problem of osteoporosis in men has recently been recognized as an important public health issue. To test the hypothesis that endocrine deficiency-mediated alterations in bone metabolism might contribute to osteoporotic fracture risk in elderly men, serum levels of 25-hydroxycholecalciferol (25(OH)D), 1,25-dihydroxycholecalciferol (1,25(OH)2D), intact parathyroid hormone (PTH), testosterone, and estradiol were measured in 40 males (mean age 73 years) who were consecutively recruited within 18 h following a fracture of the proximal femur, and in an equal number of community-living older men (mean age 72 years) who served as controls. In addition, circulating osteocalcin and urinary excretion of (deoxy)pyridinoline were determined as markers of bone formation and resorption, respectively. No differences were observed between the mean serum concentrations of osteocalcin and estradiol. Serum levels of 25(OH)D, 1,25(OH)2D, and testosterone, however, were decreased in hip fracture patients. When correcting for differences in vitamin D binding protein, differences in 1,25(OH)2D did not persist, whereas serum 25(OH)D was still significantly lower in patients than in controls (6.1 +/- 4.3 vs. 7.6 +/- 2.8, p = 0.01). Similarly, a highly significant deficit was observed in the free testosterone index, calculated from total testosterone and the level of sex hormone binding globulin (2.6 +/- 1.3 vs. 8.2 +/- 2.9, p < 0.001). Serum PTH and urinary pyridinium cross-links, however, were markedly increased in the fracture group. Moreover, in fracture patients, free 25(OH)D and free testosterone were both significant and mutually independent negative predictors of (deoxy)pyridinoline excretion. Although limited by its cross-sectional design, the present study suggests that both hypovitaminosis D and androgen deficiency may predispose to bone resorption in elderly men and in turn to remodeling imbalance and fracture risk.
Age-related bone loss may be a consequence of a lack of osteoblastic formation and/or function. In vitro, the osteoblastic response to 1,25(OH)2D3, an important regulator of osteoblastic function, appears to depend on the stage of osteoblastic maturation. In this study, we examined the response to 1,25(OH)2D3 of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) secretion in primary cultures of osteoblastic cells from human trabecular bone (hOB). Forty-four bone samples were obtained from subjects undergoing knee arthroplastia, 20 aged 50-70 (64 +/- 5), and 24 >70 (73 +/- 2) years. Another 33 bone samples were obtained from subjects undergoing hip arthroplastia, 21 were aged 50-70 (64 +/- 4) and 12 >70 (75 +/- 5) years. Pooling knee and hip hOB cell cultures, we found that PICP secretion decreased after 1,25(OH)2D3 in hOB cells from the older group (>70 years). Treatment with 1,25(OH)2D3 increased ALP secretion in these cells only in the younger group (50-70 years), whereas it increased OC secretion in hOB cells in both age groups. By pooling hOB cell cultures from both age groups we found that knee hOB cells increased OC secretion, and decreased PICP secretion, after 1,25(OH)2D3. This metabolite also increased OC secretion in hip hOB cells. Considering the influence of donor age at the same skeletal site, 1,25(OH)2D3 was found to stimulate ALP secretion only in knee hOB cells in the younger group. In contrast, this metabolite decreased ALP secretion in hip hOB cells in the older group. PICP secretion decreased after 1,25(OH)2D3 only in hOB cells in the older group, at both skeletal sites. In age-matched cultures, OC secretion was lower in hip hOB cells compared with those from the knee in the older group, but was similar in these cell cultures from both skeletal sites in the younger group. OC secretion after 1,25(OH)2D3 stimulation did not show age differences in knee hOB cells, but was lower in hip hOB in the older group. In summary, our results demonstrate that the response of various osteoblastic markers to 1,25(OH)2D3 in primary cultures of hOB cells depends on the donor age and skeletal site of origin.
For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.
To perform a meta-analysis on the published studies of serum levels of 25 hydroxyvitamin D in older people with fractures of the proximal femur compared to control groups.
A 'Medline' literature search using key words vitamin D' and 'hip fractures' for the years January 1966 to June 1999, seeking only papers published in English and available from New Zealand medical libraries, was performed. Bibliographies of identified papers were also searched. Studies which compared 25 hydroxyvitamin D levels in people with a fracture of the proximal femur to an older control group were eligible for inclusion. 30 studies were identified and 28 papers could be found in New Zealand. The method of weighted Z statistics was used in the meta-analysis.
The pooled reduction in serum 25 hydroxyvitamin D for the fracture group compared to the controls was 0.66 of a standard deviation with a 95% confidence interval of 0.74 to 0.59.
Although there may be publication bias in this meta-analysis and there was some evidence of heterogeneity in the studies, there is very good evidence that older people with fracture of the proximal femur have reduced levels of vitamin D compared to controls. Older people with fracture of the proximal femur should be treated with vitamin D.
To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women (aged 47-66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37 nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above 37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid. Vitamin D supplementation should therefore be considered in this population during the winter season.
Due to their known effects on bone metabolism, vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures.
To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis.
We searched MEDLINE, EMBASE, CINAHL, LILACS, CABNAR, BIOSIS, HEALTHSTAR, Current Contents, The Cochrane Database of Systematic Reviews, the Cochrane Musculoskeletal Injuries Group trials register, and bibliographies of identified trials and reviews. Date of the most recent search: September 2000.
Any randomised or quasi-randomised trial which compared vitamin D or a vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with eligible fracture outcomes, in elderly men or women with involutional or post-menopausal osteoporosis.
Two reviewers independently assessed trial quality, by use of a nine item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. Pooling of data, where it was admissible, used pooled relative risk and fixed effects model.
Almost all estimates of treatment effects are based on single studies. Administration of vitamin D3 alone without calcium co-supplementation was not associated with any reduction in incidence of hip fracture (relative risk (RR) 1.20, 95% confidence interval (CI) 0.83, 1.75) or other non-vertebral fracture. Administration of vitamin D3 with calcium co-supplementation to frail elderly people in sheltered accommodation was associated with a reduction in incidence of hip fracture (RR 0.74, 95% CI 0.60, 0.91). In healthy younger, ambulant participants the effect on hip fracture is unknown (RR 0.36, 95% CI 0.01, 8.78), although there appears to be a significant overall effect on non-vertebral fracture incidence in this group ( RR 0.46, 95% CI 0.23,0.90). Calcitriol (1,25 dihdyroxy vitamin D) was effective in reducing the incidence of vertebral deformity (RR 0.49, 95% CI 0.25, 0.95). Calcitriol was more effective than calcium in reducing the frequency of new vertebral deformities during the third year of treatment (RR 0.28, 95% CI 0.15, 0.52). 1-alpha-hydroxy vitamin D was effective in reducing the incidence of non-vertebral fractures in a single small study of elderly people whose mobility was impaired by neurological disease (RR 0.12, 95% CI 0.02, 0.95). No statistically significant effects were found for other comparisons of vitamin D or its analogues against each other, with and without calcium supplementation.
Uncertainty remains about the efficacy of regimens which include vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further large randomised trials are currently being conducted to clarify the effectiveness of community fracture prevention programmes employing vitamin D supplementation.
To study the prevalence of hypovitaminosis D [serum 25(OH)D < or = 37 nmol L-1)] in Finnish medical in- and outpatients in a cross-sectional study.
The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured.
Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L(-1) or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L(-1) or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males.
Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population.
Osteoporosis in the elderly is a common and severe disease, vitamin D deficiency being an important causative factor. Hypovitaminosis D is frequent in old people, particularly those living in nursing homes.
We performed a cross-sectional study of 100 randomly recruited elderly institutionalized subjects. The prevalence of hypovitaminosis D and its possible repercussion on the phosphocalcium metabolism were assessed. The degree of sun exposure and the existence of co-morbidity were also recorded. Individuals with hypovitaminosis D were included in a longitudinal study (6 months' duration) aimed at assess the efficacy of treatment with calcium and two different therapeutic regimens with calcidiol (16,000 IU/week or 16,000 IU every 3 weeks).
87% of individuals had hypovitaminosis D; 21.8% of them had secondary hyperparathyroidism. The study population had a low degree of sun exposure and a high level of co-morbidity. The two doses of calcidiol led to a normalization of 25-OHD3 levels, increased calciuria and compensated secondary hyperparathyroidism, yet higher 25-OHD3 levels were achieved with the weekly therapeutic scheme.
Hypovitaminosis D prevalence appears to be very high In the elderly institutionalized population. Calcium and calcidiol supplementation normalized 25-OHD3, improved calcium absorption and compensated secondary hyperparathyroidism. Calcium and vitamin D supplementation should be employed routinely in the elderly institutionalized population.
Bone mineral density (BMD) is one of the main determinants in the pathogenesis of fractures. However, data on factors predicting longitudinal variations in BMD are still limited and incomplete. Such data would be of great importance in order to better focus prevention strategies in both the clinical setting and at the population level. The aim of the study was to investigate the predictive value of both serological and questionnaire variables for bone mass variations in healthy women participating in a population-based longitudinal study carried out in Napoli, Italy.
High completion rate (85.2%) and adequate sample size were obtained: 139 women (45 to 79 years of age) were examined at study entry and then again after two years (24 +/- 2 months) following the same protocol. They underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. BMD was measured by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Data analysis included calculation of the percent variation in BMD in the 2-year period. Longitudinal data underwent stepwise analysis for a global evaluation of mutual interactions between independent variables.
Our findings indicate that dietary and serum calcium, and serum 25(OH)vitamin D are the only independent determinants of BMD variations at the lumbar and femoral level, respectively. While the pharmacological significance of calcium and vitamin D in the therapy of established osteoporosis is still controversial, the present longitudinal data evidence their role as essential nutrients in determining the natural history of BMD variations.
To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community.
Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years.
2686 people (2037 men and 649 women) aged 65-85 years living in the general community, recruited from the British doctors register and a general practice register in Suffolk.
Fracture incidence and total mortality by cause.
After five years 268 men and women had incident fractures, of whom 147 had fractures in common osteoporotic sites (hip, wrist or forearm, or vertebrae). Relative risks in the vitamin D group compared with the placebo group were 0.78 (95% confidence interval 0.61 to 0.99, P=0.04) for any first fracture and 0.67 (0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebral fracture. 471 participants died. The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 (0.74 to 1.06, P=0.18). Findings were consistent in men and women and in doctors and the general practice population.
Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.
To assess the cost implications for a preventive treatment strategy for institutionalised elderly women with a combined 1200 mg/day calcium and 800 IU/day vitamin D(3) supplementation in seven European countries.
Retrospective cost effectiveness analysis based on a prospective placebo-controlled randomised clinical trial.
Recently published cost studies in seven European countries. Clinical results from Decalyos, a 3-year placebo-controlled study in elderly institutionalised women. TRIALS: Decalyos study, with 36 months follow-up of 3270 mobile elderly women living in 180 nursing homes, allocated to two groups. One group received 1200 mg/day elemental calcium in the form of tricalcium phosphate together with 800 IU/day (20 microg) of cholecalciferol (vitamin D(3)), the other placebo.
In the 36 months analysis of the Decalyos study, 138 hip fractures occurred in the group of 1176 women, receiving supplementation and 184 hip fractures in the placebo group of 1127 women. The mean duration of treatment was 625.4 days. Adjusted to 1000 women, 46 hip fractures were avoided by the calcium and vitamin D(3) supplementation. For all countries, the total costs in the placebo group were higher than in the group receiving supplementation, resulting in a net benefit of 79000-711000 per 1000 women.
This analysis suggests that the supplementation strategy is cost saving. The results may underestimate the net benefits, as this treatment has also shown to be effective in decreasing the incidence of other non-vertebral fractures in elderly institutionalised women.