Vitamin C supplement use and bone mineral density in postmenopausal women.

Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity, a marker for osteoblast formation. Studies of dietary vitamin C intake and the relation with bone mineral density (BMD) have been conflicting, probably because of the well-known limitations of dietary nutrient assessment questionnaires. The purpose of this study was to evaluate the independent relation of daily vitamin C supplement use with BMD in a population-based sample of postmenopausal women. Subjects were 994 women from a community-based cohort of whom 277 women were regular vitamin C supplement users. Vitamin C supplement use was validated. Daily vitamin C supplement intake ranged from 100 to 5,000 mg; the mean daily dose was 745 mg. Average duration of use was 12.4 years; 85% had taken vitamin C supplements for more than 3 years. BMD levels were measured at the ultradistal and midshaft radii, hip, and lumbar spine. After adjusting for age, body mass index (BMI), and total calcium intake, vitamin C users had BMD levels approximately 3% higher at the midshaft radius, femoral neck, and total hip (p < 0.05). In a fully adjusted model, significant differences remained at the femoral neck (p < 0.02) and marginal significance was observed at the total hip (p < 0.06). Women taking both estrogen and vitamin C had significantly higher BMD levels at all sites. Among current estrogen users, those also taking vitamin C had higher BMD levels at all sites, with marginal significance achieved at the ultradistal radius (p < 0.07), femoral neck (p < 0.07), and total hip (p < 0.09). Women who took vitamin C plus calcium and estrogen had the highest BMD at the femoral neck (p = 0.001), total hip (p = 0.05), ultradistal radius (p = 0.02), and lumbar spine. Vitamin C supplement use appears to have a beneficial effect on levels of BMD, especially among postmenopausal women using concurrent estrogen therapy and calcium supplements.     

Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study.

Homocysteine and related factors were evaluated as risk factors for subsequent hip fractures among 4766 elderly men and women. High levels of homocysteine and low levels of folate predicted fracture, whereas vitamin B12 and genotypes were not related to fracture risk. High homocysteine may be a modifiable risk factor for hip fracture. INTRODUCTION: Elevated plasma total homocysteine (tHcy) and deficiencies of folate and vitamin B12 are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298C-->T polymorphisms predicted hip fracture. MATERIALS AND METHODS: This was a population-based prospective study of 2639 women and 2127 men who were 65-67 yr at enrollment in 1992-1993. Information on hip fracture was obtained from computerized records of discharge diagnoses from all hospitalizations in the region in the period between enrollment and November 30, 2005. Cox proportional hazard regression was used to estimate fracture risk according to levels of plasma tHcy, folate, and vitamin B12 and for different genotypes. RESULTS: Over a median follow-up period of 12.6 yr, hip fracture was recorded in 184 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (>or=15 microM) compared with low levels (<9.0 microM) of tHcy was 2.42 (1.43-4.09) among women and 1.37 (0.63-2.98) among men. Dose-response analyses indicated a positive association between plasma tHcy and risk of fracture in both sexes and a negative association between plasma folate and risk of fracture among women only. Plasma vitamin B12 level or MTHFR genotype was not significantly related to risk of fracture after adjustments for confounding factors. The association between tHcy and risk of hip fracture was only slightly weakened by adjustments for plasma levels of vitamin B12 and folate. CONCLUSIONS: tHcy seems to be a predictor for hip fracture among elderly men and women. Folate was a predictor among women only, whereas vitamin B12 and MTHFR genotype did not predict hip fracture. Our data corroborate the hypothesis that homocysteine may play a role in the pathogenesis of osteoporotic fractures.     

Association of plasma folate, plasma total homocysteine, but not methylenetetrahydrofolate reductase C667T polymorphism, with bone mineral density in postmenopausal Iranian women: a cross-sectional study

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been well documented to cause hyperhomocysteinemia, and recent studies suggest an association of C677T mutation of methylenetetrahydrofolate reductase with low bone mineral density (BMD). In this study, the association of plasma total homocysteine (Hcy), plasma folate, and vitamin B12 as well as methylenetetrahydrofolate reductase C667T polymorphism with bone mineral density at neck of femur and lumbar spine in 271 postmenopausal Iranian women was investigated. Bone mineral density was measured by dual-energy X-ray absorptiometry. Restriction fragment length polymorphism was used for genotyping the methylenetetrahydrofolate reductase polymorphism. Plasma total homocysteine, plasma folate, and vitamin B12 were also determined. The bone mineral densities at the neck of femur and lumbar spine together with other clinical characteristics among methylenetetrahydrofolate reductase genotypes (CC, CT, and TT) were examined. Bone mineral densities at both neck of femur (r = -0.18, P = 0.003) and lumbar spine (r = -0.16, P = 0.01) were significantly and negatively correlated with the logarithm of plasma total homocysteine. Bone mineral density at the lumbar spine was also significantly and positively associated with plasma folate (r = 0.14, P = 0.02). However, no correlation between methylenetetrahydrofolate reductase polymorphism with bone mineral density at neck of femur (r = -0.01, P = 0.81) and lumbar spine (r = -0.04, P = 0.51) was observed. The negative association of plasma total homocysteine with bone mineral density was no longer significant when adjusted for folate and vitamin B12. Plasma folate and age were the main predictors of plasma total homocysteine explaining 15.3% and 5.2% of the variance of plasma total homocysteine, respectively. Methylenetetrahydrofolate reductase polymorphism, however, was not associated with plasma folate (r = 0.086, P = 0.17) or vitamin B12 (r = 0.05, P = 0.4). Plasma folate was one of the main predictors explaining 3.0% and 1.7% of variance of the bone mineral density at femoral neck and lumbar spine, respectively. Results from this study suggest hyperhomocysteinemia as a result of folate deficiency, but not methylenetetrahydrofolate reductase polymorphism, is independently associated with low bone mineral density and may contribute to the pathogenicity of osteoporosis in postmenopausal Iranian women.     

Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study

We have previously found BMD and fracture risk to be significantly associated with the MTHFR (C677T) polymorphism in healthy postmenopausal women in the first years after menopause. Since then, other cohort studies have suggested that sufficient intake of riboflavin and/or folate may have the potential to prevent development of low BMD in women with the TT genotype. This could to some extent explain why this polymorphism is associated with low BMD or fracture in some study populations and not in others. It would also indicate that fractures associated with the TT genotype could be preventable by vitamin B supplementation. We have, therefore, reviewed baseline food record data from our original study to determine if BMD and fracture associations with the MTHFR genotype depended on the intake of folate, riboflavin, or other members of the vitamin B complex, associated with homocysteine metabolism. We analyzed genotype, BMD, and dietary records from 1700 healthy postmenopausal women who participated in the DOPS study. For the assessment of fracture risk, we used longitudinal observations from 854 women in the control group who remained compliant with their initial allocation of no treatment. Riboflavin intake was significantly correlated with femoral neck (FN) BMD in women with the TT genotype (r = 0.24, P < 0.01). FN and lumbar spine (LS) BMD were only associated with the MTHFR genotype in the lowest quartile of riboflavin intake. At the FN, similar threshold effects were shown for folate, vitamin B12, and vitamin B6. Among these vitamin B complex members, stepwise regression analysis identified riboflavin as the only significant predictor of FN BMD in the TT genotype. In conclusion, we confirm reports that BMD in the MTHFR TT genotype is only significantly reduced in the lowest quartile of riboflavin, B12, B6, and folate intake, at least at the time of menopause. Vitamin B supplementation would only be expected to benefit BMD in about 2% of the population, i.e., those with the TT genotype and low vitamin B intake.     

Association of dietary and biochemical measures of vitamin K with quantitative ultrasound of the heel in men and women

Introduction Low vitamin K nutritional status is associated with increased fracture risk but is inconsistently related to bone mineral density (BMD), suggesting that vitamin K may affect components of bone strength not measured by BMD, such as microarchitecture. Quantitative ultrasound (QUS) may assess trabecular orientation, providing information on the mechanical properties of bone and may serve as a potential alternative to BMD for gaining insight to the relation between vitamin K and bone strength. We therefore examined the association of vitamin K nutritional status measured in several different ways with QUS in men and women who participated in the Framingham Osteoporosis Study. Methods From 1996 to 2001, broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus (heel) were measured in 583 men and 768 women (mean age 59 years). Vitamin K nutritional status was assessed between 1995 and 1998 by three separate measures: plasma phylloquinone concentration, serum percent undercarboxylated osteocalcin (%ucOC) and dietary vitamin K intake. Multiple linear regression analyses were used to calculate regression coefficients in order to evaluate the associations between both measures of QUS and each measure of vitamin K nutritional status. Regression analyses were conducted separately for subgroups of participants defined by gender, menopause status and current use of estrogen replacement medication. Results Among the men, plasma phylloquinone concentration was positively associated with both BUA (P<0.01) and SOS (P=0.02) of the heel. Neither serum %ucOC nor dietary vitamin K intake, however, was associated with QUS measures. Among women, none of the three measures of vitamin K nutritional status were associated with either BUA or SOS, regardless of menopause status or use of estrogen. Although QUS is associated with vitamin K nutritional status in men, the observed relation was not consistent among subgroups of participants. Conclusion These findings suggest that QUS may not be the best method for elucidating the role of vitamin K on the skeleton. From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine, Framingham, Massachusetts, USA.     

Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort.

The role of dietary silicon in bone health in humans is not known. In a cross-sectional, population-based study (2847 participants), associations between dietary silicon intake and BMD were investigated. Dietary silicon correlated positively and significantly with BMD at all hip sites in men and premenopausal women, but not in postmenopausal women, suggesting that increased silicon intake is associated with increased cortical BMD in these populations. INTRODUCTION: Osteoporosis is a burgeoning health and economic issue. Agents that promote bone formation are widely sought. Animal and cellular data suggest that the orthosilicate anion (i.e., dietary silicon) is involved in bone formation. The intake of silicon (Si, approximately 30 mg/day) is among the highest for trace elements in humans, but its contribution to bone health is not known. MATERIALS AND METHODS: In a cross-sectional, population-based study, we examined the association between silicon intake and bone mineral density (BMD) in 1251 men and 1596 pre- and postmenopausal women in the Framingham Offspring cohort (age, 30-87 years) at four hip sites and lumbar spine, adjusting for all potential confounding factors known to influence BMD and nutrient intake. RESULTS: Silicon intake correlated positively with adjusted BMD at four hip sites in men and premenopausal women, but not in postmenopausal women. No significant association was observed at the lumbar spine in any group. Categorical analysis by Si intake, or energy-adjusted Si intake, supported these findings, and showed large differences in BMD (up to 10%) between the highest (> 40 mg Si/day) and lowest (< 14 mg Si/day) quintiles of silicon intake. A significant association at the lumbar spine in men was also observed. Further analyses indicated that some of the effects seen for moderate consumption of alcoholic beverages on BMD might be attributed to Si intake. CONCLUSIONS: These findings suggest that higher dietary silicon intake in men and younger women may have salutary effects on skeletal health, especially cortical bone health, that has not been previously recognized. Confirmation of these results is being sought in a longitudinal study and by assessment of the influence of silicon intake on bone markers in this cohort.     

Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans

Recent studies have found a connection between hyperhomocysteinemia and hip fracture. If this association is causal, it could be mediated through detrimental effects of low B-vitamin status on bone mineral density (BMD). Studies have linked homocysteine (Hcy) and the established Hcy determinants folate and vitamin B12, to BMD, but results have been inconsistent. Furthermore, only one study considered the specific marker of tissue vitamin B12 status, methylmalonic acid (MMA), and none have considered red blood cell (RBC) folate. To further explore associations between Hcy and B-vitamin status indicators and bone health, we used data collected on older (i.e., aged >55 years) men and women who underwent DEXA scans of the hip as participants in phase 2 of the third U.S. National Health and Nutrition Examination Survey (n = 1550). We used BMD at the total hip as a continuous outcome variable in some analyses. In others, we used osteoporosis defined on a sex- and race/ethnicity-specific basis according to World Health Organization (WHO) guidelines. After adjusting for demographic factors, body mass index, and other osteoporosis risk factors, BMD decreased and osteoporosis increased significantly with increasing serum MMA quartile category (P < 0.01). Serum vitamin B12 was related to BMD in dose-response fashion up to about 200 pmol/L, and subjects with serum Hcy > or = 20 micromol/L had significantly lower BMD than subjects with serum Hcy < 10 micromol/L. Furthermore, the OR (95% CI) relating a serum vitamin B12 concentration below the 25th percentile to osteoporosis/osteopenia was 2.0 (1.0-3.9), and dose-response trends relating both serum B12 and Hcy to this outcome were marginally statistically significant. Neither serum nor RBC folate was related to BMD or osteoporosis. We conclude that Hcy and vitamin B12 status indicators are associated with BMD in older Americans. Whether this association reflects a causal relation remains unclear and merits further study in light of age-related declines in B12 status and BMD, and the need for low-risk, easily implemented strategies for osteoporosis prevention.     

维生素D、维生素B12和同型半胱氨酸水平与绝经后女性骨密度的相关性研究

目的探索绝经后非骨质疏松症和骨质疏松症女性患者高半胱氨酸、维生素D、维生素B_(12)和骨密度(bone mineral density,BMD)之间的关系。方法选取2017年8～12月在我院就诊的138名女性作为研究对象,根据骨密度将绝经后女性分为骨质疏松组(n=58)和非骨质疏松组(n=80)。记录两组患者的体质量指数(body mass index,BMI)、年龄、腰围等一般资料,检测腰椎L_(1～4)前后位、左侧股骨近端的BMD,测定血清同型半胱氨酸、维生素B_(12)、维生素D、碱性磷酸酶、钙、磷水平。分析两组患者不同指标的差异以及高半胱氨酸、维生素D、维生素B_(12)和BMD之间的相关性。结果两组患者的年龄、BMI、腰围、同型半胱氨酸、维生素D、维生素B_(12)、腰椎L_(1～4)和左股骨颈骨密度比较差异有统计学意义(P均0.05);Rho相关性和回归分析表明,同型半胱氨酸与维生素D和B_(12)在绝经后非骨质疏松症和同型半胱氨酸与维生素B_(12)在绝经后骨质疏松症女性中呈显著负相关。结论高水平同型半胱氨酸可以通过绝经后非骨质疏松症患者维生素D水平和绝经后骨质疏松症女性维生素B_(12)水平预测。     

Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study.

Lifestyle and dietary factors may influence the association of IL-6 polymorphisms with bone mass. In 1574 unrelated men and women from the Framingham Offspring Cohort, we observed significant hip BMD differences between IL-6 -174 genotypes only in older women, those without estrogens, and those with a poor calcium intake. Hence, association of IL-6 polymorphisms with BMD may be limited to discrete population subgroups. INTRODUCTION: Interleukin (IL)-6 plays a central role in the pathogenesis of osteoporosis. Two functional variants in the IL-6 promoter have previously been associated with IL-6 expression, bone resorption levels, and BMD in late postmenopausal women, but results were conflicting in different populations. We hypothesized that the association between IL-6 promoter alleles and BMD may be affected by interactions with lifestyle and dietary factors known to influence bone turnover. MATERIALS AND METHODS: Among the Offspring Cohort of the Framingham Heart Study, 1574 unrelated men and women were genotyped for IL-6 -572 and -174 alleles. Interaction analyses with years since menopause, estrogen status, physical activity, smoking, dietary calcium, vitamin D, and alcohol intake were based on BMD measurements at the hip. RESULTS AND CONCLUSIONS: In models that considered only the main effects of IL-6 polymorphisms, no significant association with BMD was observed in either gender. In contrast, p values (0.003-0.096 by ANOVA) suggestive of an interaction between IL-6 -174 genotypes and years since menopause, estrogen status, dietary calcium, and vitamin D intake were observed in women (n = 819). In turn, BMD was significantly lower with genotype -174 GG compared with CC, and intermediate with GC, in women who were more than 15 years past menopause and in those without estrogens or with calcium intake <940 mg/day. In estrogen-deficient women with poor calcium intake, BMD differences between genotypes CC and GG were 10.2% at femoral neck (p = 0.012), 12.0% at trochanter (p = 0.012), and 16.8% at Ward's area (p = 0.0014). In contrast, no such interactions were observed in men (n = 755). In conclusion, IL-6 genetic variation was prominently associated with hip BMD in late postmenopausal women, those without estrogen replacement therapy, and those with inadequate calcium intake. In contrast, IL-6 polymorphisms are unlikely to be significant determinants of bone mass in other women or men.     

Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study.

Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/-4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health.     

Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation

Elevation of homocysteine is associated with an increased risk for bone fractures. Whether the risk is due to homocysteine or to the reduced levels of cofactors necessary for its metabolisation, such as folates or vitamin B12, is not completely clear. In this study we wanted to determine whether in postmenopausal women, levels of folates, homocysteine or vitamin B12 are predictive of the rate of vertebral bone mineral density (BMD) change. The study was conducted at the centre for the menopause of our university hospital. Between September 2001 and March 2002, 161 healthy postmenopausal women volunteered for a cross-sectional evaluation of BMD and levels of serum folates, homocysteine and vitamin B12. Women were recalled for a second evaluation of vertebral BMD after about 5 years. Women having used anti-resorptive therapies for more than 1 year were excluded. The analysis was possible in 117 postmenopausal women. The annual rate of vertebral BMD change was independently related to levels of folates (coefficient of regression (CR): 2.040; 95%CI: 0.483, 3.596; p=0.011), and initial BMD values (CR: -0.060; 95%CI: -0.117, -0.003; p=0.040). No significant relation was found between the change of vertebral BMD and homocysteine or vitamin B12. BMD values at the first (r=0.225; p=0.016) and the second (r=0.206; p=0.027) evaluation were related to levels of folates, but not of homocysteine or of vitamin B12. These data suggest an important role for folates deficiency in the vertebral BMD decline of postmenopausal women.     

The Relation of Dietary Vitamin C Intake to Bone Mineral Density: Results from the PEPI Study

Ascorbic acid is a required cofactor in the hydroxylations of lysine and proline necessary for collagen formation; its role in bone cell differentiation and formation is less well characterized. This study examines the cross-sectional relation between dietary vitamin C intake and bone mineral density (BMD) in women from the Postmenopausal Estrogen/Progestin Interventions Trial. BMD (spine and hip) was measured using dual energy X-ray absorptiometry (DXA). The PEPI participants (n = 775) included in this analysis were Caucasian and ranged in age from 45 to 64 years. At the femoral neck and total hip after adjustment for age, BMI, estrogen use, smoking, leisure physical activity, calcium and total energy intake, each 100 mg increment in dietary vitamin C intake, was associated with a 0.017 g/cm² increment in BMD (P= 0.002 femoral neck; P= 0.005 total hip). After adjustment, the association of vitamin C with lumbar spine BMD was similar to that at the hip, but was not statistically significant (P= 0.08). To assess for effect modification by dietary calcium, the analyses were repeated, stratified by calcium intake (>500 mg/day and ≤500 mg/day). For the femoral neck, women with higher calcium intake had an increment of 0.0190 g/cm² in BMD per 100 mg vitamin C (P= 0.002). No relation between BMD and vitamin C was evident in the lower calcium stratum. Similar effect modification by calcium was observed at the total hip: the β coefficient in the higher calcium stratum was similar to that for the total sample (β= 0.0172, P= 0.01), but no statistically significant relation between total hip BMD and vitamin C was found in the lower calcium subgroup. Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed (β= 0.0199, P= 0.024). These data are consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg. Received: 12 September 1997 / Accepted: 27 January 1998     

Serum 25-hydroxyvitamin D, bone mineral density, and non-vertebral fracture risk in community-dwelling older men: results from Mr. Os, Hong Kong

Summary

The study examined vitamin D status in relation to bone mineral density (BMD) and fracture risk in older Chinese men. Vitamin D deficiency was uncommon in this sample. Higher serum vitamin D level was associated with higher baseline BMD, but was not associated with bone loss or fracture risk.

Purpose

Vitamin D status in relation to bone health and fracture risk in Asian men is unknown. This study examined how vitamin D status was associated with BMD and fracture risk in Chinese men.

Methods

The study consisted of a cross-sectional and longitudinal design (the 4-year follow-up). Subjects included 939 and 712 men aged 65?year and older for cross-sectional analysis and longitudinal analysis, respectively. Baseline serum 25-hydroxyvitamin D (25OHD) was measured by a competitive radioimmunoassay kit. Baseline and 4-year percentage change in BMD at total hip, spine, and femoral neck was examined by dual-energy X-ray absorptiometry. Data on incident non-vertebral fractures and hip fractures in 4?years were collected. Data were collected for confounding factors: demographics, smoking, alcohol use, body mass index, physical activity, diet, season of blood measurement, and serum parathyroid hormone level. Multivariate regression analyses were performed with adjustments for confounding factors.

Results

A total of 94.1% of this sample had serum 25OHD at 50?nmol/L and over. After adjustment for potential confounding factors, higher serum 25OHD level was associated with higher baseline BMD at all measured sites. No association was observed between serum 25OHD level and percentage change in BMD or risk of non-vertebral fracture or hip fracture after adjustment for confounding factors.

Conclusions

Vitamin D deficiency was not common in this sample of Chinese men. Higher serum 25OHD level was associated with higher BMD at cross-sectional level. There was no association between serum 25OHD level and bone loss or fracture risk.     

Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women

Recent studies have suggested that hyperhomocystenemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenecity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine ( r =0.21, P =0.001) and femoral neck ( r =0.19, P =0.004) than was plasma 5-MTHF (lumbar spine; r =0.14, P =0.03 and femoral neck; r =0.17, P =0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenecity of osteoporosis in postmenopausal women.     

Risk factors for decreased bone density and effects of HIV on bone in the elderly

SUMMARY: Most studies of bone density in HIV-infected individuals focus on young men. This study compares differences in bone density in elderly HIV positive men and women to HIV negative controls. Bone density was lower in the lumbar spine and hip in the HIV-infected group. Antiretrovirals may be associated with decreased bone mineralization. INTRODUCTION: Individuals with human immunodeficiency virus (HIV) may be at increased risk for osteoporosis. Prolonged exposures to HIV and/or antiretroviral therapy are possible causes for this association. This study compares differences in bone mineral density (BMD) in elderly HIV positive men and women to HIV negative controls. METHODS: A cross-sectional study was conducted among 57 HIV-infected and 47 HIV negative subjects over age 55. BMD at the lumbar spine and total hip and markers of bone turnover were compared. RESULTS: BMD was borderline lower in the lumbar spine and significantly lower in the hip in the HIV-infected group. Controlling for age, sex, race and body mass index, differences between the groups were significant at both sites. There was no difference in markers of bone turnover between the groups. Tenofovir use was significantly associated with decreased BMD at the spine while protease inhibitor use was significantly associated with decreased BMD at the hip. CONCLUSION: Elderly men and women with HIV have lower bone mass than HIV negative controls. Decreased body mass index was the most important risk factor associated with decreased BMD. Bone demineralization was observed among HIV-infected subjects receiving either tenofovir or a protease inhibitor.     

Role of B12 and Homocysteine Status in Determining BMD and Bone Turnover in Young Indians

Vitamin B(12) (B(12)) deficiency and hyperhomocysteinemia (HHcy) are independent risk factors for low bone mineral density (BMD) and fracture risk. We studied the role of HHcy and B(12) deficiency in determining the peak bone mass in Indians. Randomly selected 151 healthy young adult subjects (females 100, mean age: 26 yr) underwent evaluation of dietary intake of calcium and B(12); sun exposure; estimation of BMD by dual-energy X-ray absorptiometry at total hip, forearm, and lumbar spine; serum 25(OH)D(3); intact parathyroid hormone; B(12); homocysteine (Hcy); and bone turnover markers (BTMs) serum crosslaps, N-mid osteocalcin, and bone-specific alkaline phosphatase. Hypovitaminosis D (serum 25OHD(3)<20 ng/mL) and serum ALP level >150 IU/L were seen in 83% and 27%, respectively. Median serum B(12) and Hcy levels were 140 pg/mL (interquartile range [IQR]: 72-230 pg/mL) and 18 μmol/L (IQR 14-32 μmol/L); B(12) deficiency (serum B(12)<200 pg/mL) and HHcy (serum Hcy>30 μmol/L) were present in 71% and 68%, respectively. Low BMD (Z-score <-2.0) was present in 17% of subjects. There was no significant correlation between serum Hcy, folate, B(12), BTM, and BMD. BMD was predicted by height, weight, and body mass index. Young Indian healthy adults have high prevalence of hypovitaminosis D, B(12) deficiency, and HHcy. There is no correlation of serum B(12), folate, and Hcy status with BTMs and BMD in young, healthy, vegetarian Indian adults. Anthropometric variables predict BMD in young Indians.     

Genetic and environmental determinants of peak bone mass in young men and women.

Peak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER) a, and collagen type Ialpha1 (COLIA1) genes in relation to other factors such as birth weight, lifestyle diet, and exercise in a population-based cohort of 216 women and 244 men in their early 20s. Stepwise multiple regression analysis showed that body weight was the strongest predictor of bone mineral density (BMD) in women, accounting for 16.4% of the variance in spine BMD and 8.4% of the variance in femoral neck BMD. Other significant predictors were VDR genotype (3.8%) and carbohydrate intake (1.6%) at the spine and vitamin D intake (3.4%) and ER genotype (3.4%) at the femoral neck. Physical activity was the strongest predictor of BMD in men, accounting for 6.7% of the variance at the spine and 5.1% at the hip. Other significant predictors were body weight (5%) and ER PvuII genotype (2.8%) at the spine and weight (3.4%) and alcohol intake (2%) at the femoral neck. Birth weight was not a significant predictor of BMD at either site but COLIA1 genotype significantly predicted birth weight in women, accounting for 4.3% of the variance. We conclude that peak bone mass is regulated by an overlapping but distinct set of environmental and genetic influences that differ in men and women. However, much of the variance in BMD was unexplained by the variables studied here, which suggests that either most of the genes that regulate BMD remain to be discovered or major environmental influences on BMD exist that have not yet been identified.     

A systematic review of the effect of alendronate on bone mineral density in men.

Alendronate is known to increase bone mineral density (BMD) at the lumbar spine and hip in women, but less information is available in men. We conducted a systematic review of randomized controlled trials to determine whether oral alendronate improves BMD at the lumbar spine and hip in men with low bone mass or prevalent fractures, compared with men treated with placebo, calcium, or vitamin D. In three trials in men, BMD (measured by dual-energy X-ray absorptiometry) increased at 2-3 yr (compared to baseline) at the lumbar spine and femoral neck in alendronate-treated patients compared to controls. The pooled estimates of changes in BMD with 10 mg of alendronate daily compared to controls were as follows: 7.8% over 2-3 yr (95% confidence interval [CI] = 4.8- 10.8) at the lumbar spine and 3.8% (95% CI = 2.3-5.3) at the femoral neck (p < 0.001 for treatment effect in each analysis). Statistically significant heterogeneity of treatment effect was noted between trials. We conclude that 10 mg of oral daily alendronate is significantly associated with increase in BMD at the lumbar spine and hip in men over 2-3 yr and that these changes are similar to those previously observed in postmenopausal women.     

Low Vitamin D Levels in Outpatient Postmenopausal Women from a Rheumatology Clinic in Madrid, Spain: Their Relationship with Bone Mineral Density

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. Received: 2 July 1999 / Accepted: 3 March 2000     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.