Vitamin D supplementation and bone mineral density in early postmenopausal women

BACKGROUND: Increased vitamin D intake may preserve or increase bone mineral density (BMD) in older persons. OBJECTIVE: A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone. DESIGN: One hundred eighty-seven women who were >or= 1 y postmenopausal were randomly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind, placebo-controlled format. The BMD of the proximal forearm, lumbar spine, femoral neck, Ward's triangle, and femoral trochanter was measured at 6-mo intervals by osteodensitometry. RESULTS: During the 2-y period, there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2). Both groups significantly (P < 0.005) gained BMD in Ward's triangle and the femoral trochanter but significantly (P < 0.005) lost bone in the proximal radius. There was no significant change in the lumbar spine or femoral neck BMD. CONCLUSION: In younger postmenopausal women ( age: 56 y) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range, the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone.     

Vitamin D status and bone health in healthy Thai elderly women

Objective

The prevalence of hypovitaminosis D varies in different countries. Therefore, the current study was designed to assess vitamin D status and bone health in elderly women in Thailand, which is situated near the equator.

Methods

This cross-sectional study was performed in 446 healthy women aged 60-97 y.

Results

Serum 25-hydroxyvitamin D (25(OH)D) was 67.6 ± 15.7 (mean ± SD) nmol/L. Daily calcium intake was 309.5 ± 147.2 mg/d. Serum 25(OH)D levels tended to decline with bone mineral density (BMD) status. Based on functional health-based reference values, plasma-intact parathyroid hormone began to rise below serum 25(OH)D level 70 nmol/L and increase significantly when serum 25(OH)D was ≤60 nmol/L. Thirty-two percent of elderly women had 25(OH)D insufficiency (≤60nmol/L). There was no trend toward a decrease in the concentration of serum 25(OH)D with age (r = −0.078, P = 0.10) and no significant inverse relationship with plasma intact parathyroid hormone values (r = −0.079, P = 0.097). However, a positive relationship was observed between serum 25(OH)D level and femoral neck BMD (r = 0.156, P = 0.001) but not lumbar spine L₂-L₄ BMD (r = 0.093, P = 0.050). In addition, BMD at the femoral neck but not lumbar spine of the vitamin D insufficiency group was significantly lower than that of the vitamin D sufficiency group.

Conclusion

The optimum level of serum 25(OH) value in Thai elderly women should be higher than 70 nmol/L. Vitamin D insufficiency is observed in one-third of elderly women in Bangkok.     

Vitamin D inadequacy in Belgian postmenopausal osteoporotic women

Background  

Inadequate serum vitamin D [25(OH)D] concentrations are associated with secondary hyperparathyroidism, increased bone turnover and bone loss, which increase fracture risk. The objective of this study is to assess the prevalence of inadequate serum 25(OH)D concentrations in postmenopausal Belgian women. Opinions with regard to the definition of vitamin D deficiency and adequate vitamin D status vary widely and there are no clear international agreements on what constitute adequate concentrations of vitamin D.     

Vitamin D status among postmenopausal Malaysian women

Serum levels of 25-hydroxyvitamin D (25 (OH) D) were determined in 276 (103 Malays and 173 Chinese) postmenopausal women, aged 50 to 65 years. The level of 25 (OH) D was significantly lower in the postmenopausal Malay women (44.4 +/-10.6 nmol/L) compared to the Chinese women (68.8 +/- 15.7 nmol/L) (P<0.05). There were 27% Malay women with serum 25 (OH) D in the range of 50 - 100 nmol/L (defined as lowered vitamin D status, or hypovitaminosis D) and 71% with levels in the range of 25 - 50 nmol/L (defined as vitamin D insufficiency) compared to 87% and 11% Chinese women respectively. Serum 25 (OH) D was found to significantly correlate with BMI, fat mass and PTH level. Multivariate analyses showed that race has a strong association with vitamin D status. The high prevalence of inadequate levels of serum vitamin D found in our study may have important public health consequences and warrants the development of a strategy to correct this problem in the older adult Malaysian population.     

Vitamin D intake and status in Irish postmenopausal women

OBJECTIVE: The objective of this study was to assess vitamin D status during late-summer and late-winter/early-spring in postmenopausal Irish women, and whether it was influenced by vitamin D-containing supplement use. DESIGN: A longitudinal observational study. SETTING: Cork City, Ireland (51 degrees north). SUBJECTS: A total of 59 apparently healthy, free-living, postmenopausal women aged between 51 and 69 y were sampled during February/March 2002. Of these, 48 and 47 returned during August/September 2002 and February/March 2003, respectively. None of the women were suffering from any medical condition likely to affect vitamin D status. Fasting serums were collected and analysed for 25-hydroxyvitamin D (25 (OH) D) and parathyroid hormone (PTH) by enzyme immunoassays. RESULTS: Mean daily intake of vitamin D was 3.2 microg from food sources alone and 5.8 microg when vitamin D-containing supplements were included (P<0.01). Serum 25 (OH) D was significantly lower (P<0.001) during February/March 2002 than both August/September 2002 and February/March 2003. Serum 25 (OH) D was also significantly higher (P < or = 0.05) in women who were vitamin D-containing supplement users than nonusers during all three sampling points. Between 17 and 36% of women had inadequate vitamin D status (defined as serum 25 (OH) D <40 nmol/l) during late-winter, but only 4% had inadequate vitamin D status during late-summer. Serum 25 (OH) D was inversely related to serum PTH (r = -0.33; P = 0.028). CONCLUSION: Suboptimal vitamin D status is common in postmenopausal Irish women during winter. Vitamin D supplementation is associated with improved vitamin D status, even during summertime.     

Vitamin D and bone health in early life

Prolonged vitamin D deficiency resulting in rickets is seen mainly during rapid growth. A distinct age distribution has been observed in the Copenhagen area where all registered hospital cases of rickets were either infants and toddlers or adolescents from immigrant families. Growth retardation was only present in the infant and toddler group. A state of deficiency occurs months before rickets is obvious on physical examination. Growth failure, lethargy and irritability may be early signs of vitamin D deficiency. Mothers with low vitamin D status give birth to children with low vitamin D status and increased risk of rickets. Reports showing increasing rates of rickets due to insufficient sunlight exposure and inadequate vitamin D intake are cause for serious concern. Many countries (including the USA from 2003) recommend vitamin D supplementation during infancy to avoid rickets resulting from the low vitamin D content of human milk. Without fortification only certain foods such as fatty fish contain more than low amounts of vitamin D, and many children will depend entirely on sun exposure to obtain sufficient vitamin D. The skin has a high capacity to synthesize vitamin D, but if sun exposure is low vitamin D production is insufficient, especially in dark-skinned infants. The use of serum 25-hydroxyvitamin D to evaluate vitamin D status before development of rickets would be helpful; however, there is no agreement on cut-off levels for deficiency and insufficiency. Furthermore, it is not known how marginal vitamin D insufficiency affects children's bones in the long term.     

Vitamin D and bone health: potential mechanisms

Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms.     

Diet,weight, cytokines and bone health in postmenopausal women

Objectives

To investigate diet and nutrition-related factors associated with bone loss in a group of postmenopausal (PM) women. Nutritional intake, inflammatory markers and body composition (weight, body mass index, fat/lean mass) were analysed for associations with bone mineral density (BMD).

Design

A cross sectional study examining correlations between BMD (Duel-energy X ray absorptiometry; (DXA) and dietary intake (3-day diaries), body composition and plasma bone and inflammatory markers: C-terminal telopeptide of type I collagen (CTX) and procollagen type I N propeptide (P1NP), C- reactive protein (CRP), interleukin 6 and 10 (IL-6, IL-10), tumour necrosis factor (TNF) and osteoprotegerin (OPG).

Setting

Community dwelling women from the Auckland, Hawke’s Bay and Manawatu regions in New Zealand.

Participants

142 healthy, PM women aged 50–70 years.

Results

OPG (per kilogram fat mass) was increased in women with osteoporosis (p<0.001) compared to groups classified with normal BMD and osteopenia. Protein, vitamin B12, zinc, potassium and dairy intake were all positively correlated with higher BMD while dairy and potassium intakes also inversely correlated with CTX. Body composition (weight, BMI and fat/lean mass) had strong positive associations with BMD. Multiple regression analysis showed body weight, potassium and dairy intake were predictors of increased BMD in PM women and explained 39% (r²=0.39, p< 0.003) of variance.

Conclusion

BMD was negatively correlated with OPG and positively with weight, dairy and potassium intake. This study highlights the importance of maintaining adequate body weight and emphasising dairy and potassium predominantly sourced from fruit/vegetables to reduce bone loss at midlife.     

Dietary calcium intake, vitamin D status, and bone health in postmenopausal women in rural Pakistan

The high prevalence of osteoporosis in Pakistan is of public-health concern. However, there is a paucity of information regarding nutrition and bone density in rural communities. The purpose of this study was to evaluate the dietary and lifestyle factors that impact bone health in Nahaqi. Data were collected from 140 postmenopausal women using an interviewer-administered 24-hour dietary recall questionnaire. Bone mineral density was estimated using the quantitative ultrasound index (QUI). Serum 25(OH)D was measured in fasting blood samples. The QUI scores revealed that 42% and 29% of the women had T-scores, indicative of osteopaenia and osteoporosis respectively. The mean calcium intake was 346 mg/d, which is less than 50% of the recommended daily intake. The QUI correlated with 25(OH)D after controlling for age (p=0.021, r=0.41, r2=0.168). Vitamin D deficiency and low intake of dietary calcium are two key factors contributing to poor bone health in this population.     

Vitamin D, hydroxyapatite, and calcium gluconate in treatment of cortical bone thinning in postmenopausal women with primary biliary cirrhosis

Women with primary biliary cirrhosis malabsorb calcium, phosphate and vitamin D, and develop accelerated cortical bone thinning. We have assessed the value of parenteral vitamin D, oral hydroxyapatite (HA), and calcium gluconate (CG) in the treatment of cortical bone thinning in primary biliary cirrhosis. Sixty-four postmenopausal women with primary biliary cirrhosis were assigned randomly into three groups: one group receiving no mineral supplements (control), one group receiving HA, and one group receiving CG. All patients received parenteral vitamin D2 (100,000 IU monthly). Eleven patients withdrew from the study and 10 withdrew due to poor compliance (six HA, four CG). Over a 14-month follow-up period, none of the groups showed a significant change in serum calcium or inorganic phosphate levels. Pre- and posttreatment hand radiographs were used to assess changes in metacarpal cortical thickness using the technique of caliper radiogrammetry. Cortical bone loss occurred in the control group (p less than 0.01). The HA group showed a significant gain in cortical bone thickness (p less than 0.01), while no significant change occurred in the CG group. This study indicated that vitamin D2 does not halt metacarpal cortical bone thinning in primary biliary cirrhosis. The addition of CG prevents bone thinning, and HA promotes positive cortical bone balance.     

Vitamin D status: effects on parathyroid hormone and 1, 25-dihydroxyvitamin D in postmenopausal women

BACKGROUND: Low serum 25-hydroxyvitamin D ?25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. OBJECTIVE: Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. DESIGN: This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. RESULTS: PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ?1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations 40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. CONCLUSION: The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.     

Investigating the role of natural phyto-oestrogens on bone health in postmenopausal women

Research on the bone effects of natural phyto-oestrogens after menopause is at a relatively early stage. Published studies are few, difficult to compare and often inconclusive, due in part to design weaknesses. Currently, many questions remain to be answered including to what extent a safe daily intake may prevent postmenopausal bone loss. These questions can only be addressed by conducting well-planned, randomised clinical trials that take into consideration present knowledge in the oestrogen, phyto-oestrogen and bone fields. This review is intended to provide hints for critical decision-making about the selection of subjects, type of intervention, suitable outcome measures and variables that need to be controlled.     

Vitamin D insufficiency among postmenopausal women in urban and rural areas in Guilan, Northern Iran

This study aimed to describe vitamin D status in postmenopausal women in urban and rural areas in Guilan, northern Iran. Between October 2004 and February 2005 a group of 750 women older than 50 years was randomly selected from urban and rural areas in Guilan. The participants were interviewed to collect data on age, educational level, body weight, height, employment status, reproductive history, medications, history of illness, and supplement use. Serum 25(OH) D was measured in 646 women (427 in urban areas and 219 women in rural areas). Serum 25(OH) D levels in urban and rural postmenopausal women were 18.5 ± 13.5 ng/ml and 22.9 ± 13.8 ng/ml (P < 0.0001), respectively. In urban and rural areas, 84.7% and 79.5% of the women had serum 25(OH) D levels less than 30 ng/ml, respectively. In this study, serum vitamin D levels and prevalence of vitamin D insufficiency was related to educational level in urban women. The urban women in the lowest educational level (<5 years schooling) had a better vitamin D status than other educational groups. This study showed that a high proportion of postmenopausal women living in Guilan province had vitamin D insufficiency. Vitamin D inadequacy was more common in urban areas and especially in the upper social class. Supplement use and national strategies to prevent vitamin D insufficiency are strongly needed in this community.     

Seasonal changes in vitamin D status and bone turnover in healthy Irish postmenopausal women

OBJECTIVES: To examine the effect of season on biochemical markers of bone turnover in 51-to 75-year-old Irish women and to investigate whether such changes are related to vitamin D status. DESIGN: Longitudinal observational study. SETTING: Cork, Ireland (52 degrees N). SUBJECTS: 76 apparently healthy, free-living postmenopausal women (aged 51-75 years), not taking any medication and free from any condition likely to affect vitamin D status or calcium/bone metabolism. RESULTS: Serum 25-hydroxyvitamin D [S-25(OH)D] showed a clear seasonal variation with significantly higher (p < 0.001) values during late summer than late winter. Both urinary pyridinoline (Ur-Pyr) (p < 0.01) and deoxypyridinoline (Ur-Dpyr) (p < 0.001), but not serum parathyroid hormone or osteocalcin, showed a marked seasonal variation with lowest values during late-summer. Stratifying women into those with S-25(OH)D levels > or = or <50 nmol/L (vitamin D adequate and inadequate, respectively) during late-winter, showed that Ur-Pyr and Ur-Dpyr in both groups were significantly (p < 0.05) lower during late summer, and the magnitude of the reduction from winter to summer was similar in both groups. CONCLUSION: Seasonal changes in bone resorption markers appeared to be linked to seasonal changes in vitamin D status. Further research is needed to investigate the impact of these changes on risk of bone loss and fracture.     

Vitamin K and bone health

Vitamin K, originally recognised as a factor required for normal blood coagulation, is now receiving more attention in relation to its role in bone metabolism. Vitamin K is a coenzyme for glutamate carboxylase, which mediates the conversion of glutamate to gamma-carboxyglutamate (Gla). Gla residues attract Ca2+ and incorporate these ions into the hydroxyapatite crystals. There are at least three Gla proteins associated with bone tissue, of which osteocalcin is the most abundant and best known. Osteocalcin is the major non-collagenous protein incorporated in bone matrix during bone formation. However, approximately 30% of the newly-produced osteocalcin stays in the circulation where it may be used as an indicator of bone formation. Vitamin K deficiency results in an increase in undercarboxylated osteocalcin, a protein with low biological activity. Several studies have demonstrated that low dietary vitamin K intake is associated with low bone mineral density or increased fractures. Additionally, vitamin K supplementation has been shown to reduce undercarboxylated osteocalcin and improve the bone turnover profile. Some studies have indicated that high levels of undercarboxylated osteocalcin (as a result of low vitamin K intake?) are associated with low bone mineral density and increased hip fracture. The current dietary recommendation for vitamin K is 1 microg/kg body weight per d, based on saturation of the coagulation system. The daily dietary vitamin K intake is estimated to be in the range 124-375 microg/d in a European population. Thus, a deficiency based on the hepatic coagulation system would be unusual, but recent data suggest that the requirement in relation to bone health might be higher.     

Nutrition and lifestyle in relation to bone health and body weight in Croatian postmenopausal women

The objective was to investigate the association of nutrients and lifestyle modifiers with bone mineral density (BMD) and weight and/or body mass index (BMI) in 120 healthy Croatian postmenopausal women. The hip and spine BMD was assessed by Lunar Prodigy (GE Medical Systems). Nutrient assessment from 3-day records was analyzed using the US Department of Agriculture Food Composition Tables and the Croatian National Institute of Public Health database. Subjects were asked to record the consumption of alcohol, coffee, tea and mineral waters, the amount of salt added to foods and smoking habits, as well as involvement in recreational activities, walking and heavy housework. Spot urine samples were analyzed for calcium, magnesium, sodium, potassium and zinc and were normalized by creatinine. Alcohol showed statistically significant positive association with femur and spine BMD and its consumption was higher in subjects without osteoporosis. Urinary sodium/creatinine was significantly positively associated with femoral neck and trochanter BMD, while urinary calcium/creatinine was significantly negatively associated with trochanter, total femur and spine BMD. Consumption of mineral waters was inversely associated with weight/BMI and so were dietary fiber and magnesium. In conclusion, moderate alcohol consumption and urinary sodium were positively associated while urinary calcium was negatively associated with either hip and/or spine BMD. Mineral waters, higher fiber and magnesium intake were beneficial for weight/BMI in this population of apparently healthy Croatian women.     

Vitamin D and adverse pregnancy outcomes: beyond bone health and growth

Concerns exist about adequacy of vitamin D in pregnant women relative to both maternal and fetal adverse health outcomes. Further contributing to these concerns is the prevalence of inadequate and deficient vitamin D status in pregnant women, which ranges from 5 to 84% globally. Although maternal vitamin D metabolism changes during pregnancy, the mechanisms underlying these changes and the role of vitamin D during development are not well understood. Observational evidence links low maternal vitamin D status with an increased risk of non-bone health outcome in the mother (pre-eclampsia, gestational diabetes, obstructed labour and infectious disease), the fetus (gestational duration) and the older offspring (developmental programming of type 1 diabetes, inflammatory and atopic disorders and schizophrenia); but the totality of the evidence is contradictory (except for maternal infectious disease and offspring inflammatory and atopic disorders), lacking causality and, thus, inconclusive. In addition, recent evidence links not only low but also high maternal vitamin D status with increased risk of small-for-gestational age and schizophrenia in the offspring. Rigorous and well-designed randomised clinical trials need to determine whether vitamin D has a causal role in non-bone health outcomes in pregnancy.