Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women

Summary

The various factors that may contribute to vitamin D deficiency or insufficiency were examined among healthy Saudi pre- and postmenopausal women. Vitamin D deficiency was highly prevalent among studied Saudi women with obesity, poor sunlight exposure, poor dietary vitamin D supplementation and age as the main risk factors.

Introduction

The various factors that may contribute to vitamin D deficiency or insufficiency in relation to bone health among Saudi women are not known. The main objectives of the present study were to determine the factors influencing vitamin D status in relation to serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH), bone turnover markers (BTMs), bone mineral density (BMD), and vitamin D receptor genotype (VDR) in healthy Saudi pre- and postmenopausal women.

Methods

A total number of 1,172 healthy Saudi women living in the Jeddah area were randomly selected and studied. Anthropometric parameters, socioeconomic status, sun exposure index together with serum levels of 25(OH)D, calcitriol, intact PTH, Ca, PO4, Mg, creatinine, albumin, and biochemical BTMs were measured. BMD was measured by a dual energy X-ray absorptiometry and VDR genotypes were also determined.

Results

About 80.0% of Saudi women studied exhibited vitamin D deficiency (serum 25(OH)D?<?50.0?nmol/L) with only 11.8% of all women were considered with adequate vitamin D status (serum 25(OH)D?>?75?nmol/L). Secondary hyperparathyroidism was evident in 18.5% and 24.6% in pre- and postmenopausal women with 25(OH)D?<?50?nmol/L. Serum 25(OH)D was lower (P?<?0.001) and intact PTH higher (P?<?0.001) in the upper quintiles of body mass index (BMI) and waist-to-hip ratio (WHR). Multiple linear regression analysis showed that BMI, sun exposure index, poor dietary vitamin D supplementation, WHR, and age were independent positive predictors of serum 25(OH)D values.

Conclusions

Vitamin D deficiency is highly prevalent among healthy Saudi pre-and postmenopausal women and largely attributed to obesity, poor exposure to sunlight, poor dietary vitamin D supplementation, and age.     

Randomized Controlled Trial of the Effects of Calcium With or Without Vitamin D on Bone Structure and Bone‐Related Chemistry in Elderly Women With Vitamin D Insufficiency

There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status. The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone‐related chemistry in elderly women with vitamin D insufficiency. Three hundred two elderly women (age, 77.2 ± 4.6 yr) with serum 25(OH)D concentrations <60 nM participated in a 1‐yr randomized, double‐blind, placebo‐controlled trial. All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol (vitamin D₂) or identical placebo (control). The effects of time and time treatment interactions were evaluated by repeated‐measures ANOVA. At baseline, calcium intake was 1100 mg/d, and 25(OH)D was 44.3 ± 12.9 nM; this increased in the vitamin D group by 34% but not the control group after 1 year (59.8 ± 13.8 versus 45.0 ± 13.3 nM, p < 0.001). Total hip and total body BMD increased significantly, and procollagen type I intact N‐terminal propeptide (PINP) decreased during the study with no difference between the treatment groups (hip BMD change: vitamin D, +0.5%; control, +0.2%; total body BMD change: vitamin D, +0.4%; control, +0.4%; PINP change: vitamin D, ?3.9%; placebo, ?2.8%). Although the fasting plasma and urine calcium increased in both groups equally, there was no detectable change in serum PTH. The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption, which fell equally in both groups (vitamin D, ?17.4%; control, ?14.8%). In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency, vitamin D₂ 1000 IU for 1 year has no extra beneficial effect on bone structure, bone formation markers, or intestinal calcium absorption over an additional 1000 mg of calcium. Vitamin D supplementation adds no extra short‐term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency.     

The Effect of High-Dose Vitamin D Supplementation on Calciotropic Hormones and Bone Mineral Density in Obese Subjects with Low Levels of Circulating 25-Hydroxyvitamin D: Results from a Randomized Controlled Study

Low levels of 25-hydroxyvitamin D (25OHD) are associated with increased bone turnover and risk of fractures. Plasma 25OHD is inversely related to body mass index, and vitamin D deficiency is common in obesity. We aimed to determine whether vitamin D supplementation affects bone turnover and bone mineral density (BMD) in obese subjects. Fifty-two healthy obese men and women aged 18–50 years with plasma 25OHD levels below 50 nmol/L were randomized to 7,000 IU of cholecalciferol daily or placebo for 26 weeks. We measured plasma levels of 25OHD, parathyroid hormone (PTH), and markers of bone turnover, as well as BMD at the hip, spine, forearm, and whole body. Compared with placebo, treatment with cholecalciferol increased mean plasma 25OHD from 35 to 110 nmol/L (p < 0.00001) and significantly decreased PTH (p < 0.05). BMD increased significantly at the forearm by 1.6 ± 0.7 % (p = 0.03). The bone resorption marker C-terminal telopetide of type 1 collagen (CTX) decreased borderline significantly in the cholecalciferol group compared with the placebo group (p = 0.07). Changes in plasma 25OHD correlated inversely with changes in plasma levels of bone-specific alkaline phosphatase (r = ?0.38, p = 0.01) and CTX (r = ?0.33, p = 0.03). Changes in CTX correlated inversely with changes in spine BMD (r = ?0.45, p = 0.04). Increasing circulating 25OHD levels by cholecalciferol treatment is of importance to bone health in young obese subjects as increased levels of 25OHD are associated with a decrease in both PTH and bone turnover and with an increase in BMD at the forearm.     

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: A 1‐year double‐blind RCT in postmenopausal women

Few year‐long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D₃ at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1‐year double‐blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25‐dihydroxyvitamin D[1,25(OH)₂D], N‐terminal propeptide of type 1 collagen [P1NP], C‐terminal telopeptide of type I collagen [CTX], and fibroblast growth factor‐23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25‐hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was ?4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored. © 2013 American Society for Bone and Mineral Research.     

Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women

OBJECTIVES: To determine factors influencing serum 25 hydroxyvitamin D (25OHD) concentration and relationships between serum 25OHD concentration, bone turnover markers, bone mineral density (BMD), and vitamin D receptor (VDR) genotype in Emirati women. METHODS: Serum 25OHD, parathyroid hormone (PTH), osteocalcin (OC), vitamin D binding protein (VDBP), and urinary deoxypyrdinoline (UDPD) concentrations and VDR genotype were determined in Emirati women volunteers who were participating in a study aiming at establishing a reference database for BMD. RESULTS: Serum 25OHD concentration in the 259 women volunteers was 25.3 +/- 10.8 nmol/l (mean +/- SD), and all had vitamin D deficiency (25OHD <80 nmol/l). Mean serum 25OHD was highest in April (29.2 +/- 13.0 nmol/l), which marks the end of the short and cooler winter season, and lowest in August (18.2 +/- 5.9 nmol/l). No significant difference in 25OHD concentration was noted among Emirati women wearing different dress styles, but the mean serum 25OHD was significantly lower in comparison with non-Arab Caucasian women volunteers who dressed in a Western style (P < 0.001). Serum 25OHD correlated positively with age (r = 0.2), number of pregnancies (r = 0.16), dietary vitamin D intake (r = 0.15), serum calcium (r = 0.14), phosphorus (r = 0.14), VDBP (r = 0.15), and urinary calcium/creatinine (r = 0.2), and inversely with PTH (r = -0.22), OC (r = -0.13), and UDPD/creatinine (r = -0.15); P < 0.05 for all correlations. Multiple linear regression analysis showed that age, dietary vitamin D intake, multivitamin intake, and cooler season were independent positive predictors of serum 25OHD concentration (R(2) = 0.18). The frequencies of VDR genotypes were 36% GG, 44.1% AG, and 19.9% AA. Allele frequencies were 58% for G allele and 42% for A allele and were in Hardy-Weinberg equilibrium (x(2) = 1.44; P > 0.1). There was no statistically significant influence of VDR genotype on bone turnover or BMD. CONCLUSIONS: Vitamin D deficiency is highly prevalent in Emirati women and appears largely attributable to insufficient sunlight exposure. It is associated with increased bone turnover. VDR genotype does not appear to influence bone turnover markers or BMD in Emirati women.     

Vitamin D status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart’s Project

Summary

In girls, a plateau in parathyroid hormone (PTH) was observed at a 25-hydroxyvitamin D (25(OH)D) concentration of approximately 60 nmol/l. In boys, there was no plateau in PTH concentrations as 25(OH)D concentration increased. A 25(OH)D threshold of 60 nmol/l appears to have implications for bone health outcomes in both girls and boys.

Introduction

Our objective was to investigate if there is a threshold 25(OH)D concentration where a plateau in PTH concentration is evident and to examine the impact of this relationship on bone mineral density (BMD) and bone turnover in a representative sample of adolescents.

Methods

We conducted a cross-sectional analysis among 1,015 Northern Irish adolescents aged 12 and 15 years. Serum 25(OH)D, PTH, osteocalcin, type 1 collagen cross-linked C-telopeptide (CTx), and BMD of the nondominant forearm and heel were measured. Nonlinear regression analysis was used to model the association between 25(OH)D and PTH.

Results

In girls, a plateau in PTH was observed at a 25(OH)D concentration of approximately 60 nmol/l (PTH?=?47.146?+?370.314?×?exp^{(?0.092?×?25(OH)D)}) while no plateau in PTH was observed in boys (PTH?=?42.144?+?56.366?×?exp^{(?0.022?×?25(OH)D)}). Subjects with 25(OH)D levels <60 nmol/l had significantly higher osteocalcin concentrations (P?<?0.05) compared with those who had ≥60 nmol/l, while no significant (P?>?0.05) differences were noted for CTx concentrations. In girls only, nondominant forearm BMD but not heel BMD was significantly higher (P?=?0.046) in those with 25(OH)D concentrations?≥?60 nmol/l.

Conclusions

Serum 25(OH)D levels above 60 nmol/l in Northern Irish adolescent girls prevent an increase in serum PTH levels and maintaining 25(OH)D >60 nmol/l in both girls and boys may lead to improved bone health outcomes.     

Vitamin D Supplementation After Parathyroidectomy: Effect on Bone Mineral Density—A Randomized Double‐Blind Study

Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower bone mineral density (BMD), and an increased risk of fractures. They also have a high incidence of low vitamin D levels (25‐OH‐vitamin D <50 nmol/L) that could worsen the negative effect on the bone. In this double‐blinded clinical trial, 150 patients with PHPT were randomized, after successful parathyroidectomy (PTX), to 1‐year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D +) or calcium carbonate alone (D–). BMD was measured in the lumbar spine, femoral neck, total hip, distal and 33% radius using dual‐energy X‐ray absorptiometry (DXA) before surgery and after 1 year of study medication. Median age was 60 (range 30–80) years and there were 119 (79%) women and 31 (21%) men; 76% had 25‐OH‐D <50 nmol/L before PTX and 50% had persistent elevated parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the lumbar spine, femoral neck, and total hip was observed in both groups (D + : 3.6%, 3.2%, and 2.7%, p < 0.001, respectively; and D–: 3.0%, 2.3%, and 2.1%, respectively, p < 0.001). Patients with vitamin D supplementation also increased their BMD in distal radius (median 2.0%; interquartile range, ?1.7% to 5.4%; p = 0.013). The changes in BMD, especially in the hips, were correlated to the baseline concentrations of PTH, ionized calcium, and bone markers (p < 0.001). A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation, who also improved their BMD at 33% radius and radius ultradistal (p < 0.05). In conclusion, except for a minor improvement of radius BMD, our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest association with improvement in BMD. © 2014 American Society for Bone and Mineral Research.     

Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays

Summary

A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D.

Introduction

This study aims to compare measures of vitamin D-binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations.

Methods

DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21–80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D.

Results

Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r _s?=?0.02, p?=?0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p?<?0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (?0.34, p?<?0.001) versus free/bioavailable 25(OH)D (?0.18/?0.24 depending on DBP assay, p?≤?0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites.

Conclusions

The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health.

     

Vitamin D Status and Parathyroid Hormone Concentrations Influence the Skeletal Response to Zoledronate and Denosumab

Studies suggest that optimal vitamin D status is required for the maximal effect of antiresorptive agents. We investigated the relationship between vitamin D status, serum parathyroid hormone (PTH) concentrations, and change in bone mineral density (BMD) following iv zoledronate and denosumab. We carried out a retrospective analysis of 111 patients, mean age 70 (SD 13) years, 89 women and 22 men, prescribed zoledronate and 43 postmenopausal women treated with denosumab for osteoporosis. We measured BMD at the lumbar spine (LS) and total hip (TH), serum 25 (OH) vitamin D, PTH, and bone turnover markers (plasma CTX, P1NP) at 1 year. In patients on zoledronate, BMD increased at the LS and TH (mean LS change [SEM] = 2.6 % [0.5 %], mean TH change = 1.05 % [0.5 %], p < 0.05). A significant increase in BMD was seen at the LS only in the denosumab group (p = 0.001). Significant decreases in CTX and P1NP were observed at 12 months in both treatment groups. At baseline and at 12 months, 34 % and 23 % of the patients on zoledronate had a serum vitamin D of <50 nmol/L, respectively. The mean PTH concentration in patients with 25 (OH) vitamin D <50 nmol/L was 44 ng/L (SEM 16.6). Patients with PTH concentration <44 ng/L had significantly higher increases in TH BMD compared to those with PTH >44 ng/L (zoledronate 1.9 [0.83] vs. ?0.43 [0.81], p = 0.04; denosumab 4.1 [0.054] vs. ?1.7 [0.04], p = 0.004). Optimal vitamin D status and PTH concentrations improve the skeletal response to zoledronate and denosumab.     

A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs.

Vitamin D supplementation, when given with calcium, has been shown to increase bone mineral density (BMD) and reduce the incidence of hip fracture in elderly subjects. Despite its widespread use, the benefits of vitamin D supplementation in younger women and as a single agent are less clear. We performed a randomized co-twin, placebo-controlled, double-blind trial over 2 years to measure the effect of vitamin D3 supplementation on bone density and bone metabolism in young postmenopausal women. Seventy-nine monozygotic (MZ) twin pairs (mean age, 58.7 years; range, 47-70 years) were recruited. For each twin pair, one was randomized to 800 IU cholecalciferol/day for 2 years and the other was randomized to placebo. BMD was measured at the spine and hip and heel ultrasound at baseline, 12, 18, and 24 months. Samples were collected at 0, 3, and 6 months to measure serum calcium, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary deoxypyridinoline (DPD). In total, 64 pairs completed the study. No differences in baseline characteristics were seen between the groups. At 6 months, the treatment group had an increase in serum vitamin D [mean +/- SEM intrapair difference, 14.1+/-2.4 microg/liter (p < 0.001)]. There were no significant differences in other serum measurements or bone markers at 3 months or 6 months. At 24 months, no significant treatment effect was seen on BMD or calcaneal ultrasound change within pairs. Subanalysis of treatment response by vitamin D receptor (VDR) genotype revealed no significant difference in effect on BMD variables with treatment. On the basis of these results, vitamin D supplementation, on its own, cannot be recommended routinely as an osteoporosis prevention for healthy postmenopausal women with normal vitamin D levels under the age of 70 years.     

Wintertime Vitamin D Supplementation Inhibits Seasonal Variation of Calcitropic Hormones and Maintains Bone Turnover in Healthy Men

Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21–49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 ± 5.1 (SD) μg/d. This was a 6‐mo double‐blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 μg (800 IU), 10 μg (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S‐)25(OH)D, iPTH, bone‐specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S‐25(OH)D, S‐PTH, and S‐TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S‐BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S‐BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5–20 μg (700–800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men.     

Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: The Rancho Bernardo Study

Vitamin D (25(OH)D) increases the efficiency of intestinal calcium absorption. Low levels of serum calcium stimulate the secretion of parathyroid hormone (PTH), which maintains serum calcium levels at the expense of increased bone turnover, bone loss and increased risk of fractures. We studied the association between 25(OH)D and PTH levels, and their associations with bone mineral density (BMD), bone loss, and prevalence of hip fractures in 615 community-dwelling postmenopausal aged 50–97 years. Mean level of 25(OH)D and PTH were 102.0 nmol/l±35.0 nmol/l and 49.4 ng/l±23.2 nmol/l, respectively; 49% of women were current hormone therapy users. The overall prevalence of vitamin D insufficiency (25(OH)D<50 nmol/l) was 2%, and prevalence of high PTH levels (>65 ng/l) was 17.4%. In multiple linear regression analyses hip BMD was negatively and independently associated with PTH levels ( p =0.04), and positively and independently associated with 25(OH)D levels ( p =0.03). There were only 23 women (3.7%) who experienced a hip fracture. In age-adjusted analyses there were no significant differences of 25(OH)D and PTH levels by hip fracture status. Across the entire range of values, the overall correlation between 25(OH)D and PTH was moderate ( r =–0.20). However, after the threshold vitamin D level of 120 nmol/l, all PTH values were below 65 ng/l. Further studies are necessary to identify the optimal vitamin D levels necessary to prevent secondary hyperparathyroidism.     

The Association between Parathyroid Hormone, Vitamin D and Bone Mineral Density in 70-Year-Old Icelandic Women

Parathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64° N), where daily intake of cod liver oil is common and mean calcium intake is high. ln PTH correlated inversely with 25(OH)D (r=−0.26, p<0.01). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R ²= 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis. Received: 3 January 2000 / Accepted: 10 April 2000     

Vitamin D Status,Parathyroid Function,Bone Turnover,and BMD in Postmenopausal Women With Osteoporosis: Global Perspective

Poor vitamin D status is common in the elderly and is associated with bone loss and fractures. The aim was to assess worldwide vitamin D status in postmenopausal women with osteoporosis according to latitude and economic status, in relation to parathyroid function, bone turnover markers, and BMD. The study was performed in 7441 postmenopausal women from 29 countries participating in a clinical trial on bazedoxifene (selective estrogen receptor modulator), with BMD T‐score at the femoral neck or lumbar spine ≤ ?2.5 or one to five mild or moderate vertebral fractures. Serum 25(OH)D, PTH, alkaline phosphatase (ALP), bone turnover markers osteocalcin (OC) and C‐terminal cross‐linked telopeptides of type I collagen (CTX), and BMD of the lumbar spine, total hip, femoral neck, and trochanter were measured. The mean serum 25(OH)D level was 61.2 ± 22.4 nM. The prevalence of 25(OH)D <25, 25–50, 50–75, and >75 nM was 5.9%, 29.4%, 43.5%, and 21.2%, respectively, in winter and 3.0%, 22.2%, 47.2%, and 27.5% in summer. Worldwide, a negative correlation between 25(OH)D and latitude was observed. With increasing 25(OH)D categories of <25, 25–50, 50–75, and >75 nM, mean PTH, OC, and CTX were decreasing (p < 0.001), whereas BMD of all sites was increasing (p < 0.001). A threshold in the positive relationship between 25(OH)D and different BMD parameters was visible at a 25(OH)D level of 50 nM. Our study showed a high prevalence of low 25(OH)D in postmenopausal women with osteoporosis worldwide. Along with latitude, affluence seems to be an important factor for serum 25(OH)D level, especially in Europe, where it is strongly correlated with latitude.     

Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women

Summary

We evaluated vitamin D status in HIV+ and HIV? postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy.

Introduction

To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women.

Methods

In this cross-sectional study, 89 HIV+ and 95 HIV? postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry.

Results

The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV? women (74-78%) had insufficient levels (<30?ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r?=?0.32; p?<?0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)₂D and CD4 count or between serum 25OHD, 1,25(OH)₂D or PTH and type of ART.

Conclusions

In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.     

Association of serum sclerostin with bone mineral density, bone turnover, steroid and parathyroid hormones, and fracture risk in postmenopausal women: the OFELY study

Summary

Sclerostin is a key regulator of bone formation. In a population of 572 postmenopausal women (mean age, 67 years) followed prospectively for a median of 6 years, there was no significant association between baseline levels of serum sclerostin and incidence of all fractures which occurred in 64 subjects.

Introduction

Sclerostin, an osteocyte soluble factor, is a major negative regulator of osteoblastic activity. Circulating sclerostin levels were reported to increase with age and to be modestly associated with bone mineral density (BMD) and bone turnover, but there are no data on the association with fracture risk.

Methods

We investigated 572 postmenopausal women (mean age, 67?±?8.5 years) from the OFELY population-based cohort. The associations of serum sclerostin measured with a new two-site ELISA and spine and hip BMD by DXA, serum β-isomerized C-terminal crosslinking of type I collagen (CTX), intact N-terminal propeptide of type I collagen (PINP), intact PTH, 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone, and fracture risk were analyzed. At the time of sclerostin measurements, 98 postmenopausal women had prevalent fractures. After a median of 6 years (interquartile range, 5–7 years) follow-up, 64 postmenopausal sustained an incident fracture.

Results

Serum sclerostin correlated positively with spine (r?=?0.35, p?<?0.0001) and total hip (r?=?0.25, <0.0001) BMD. Conversely, serum sclerostin was weakly negatively associated with the bone markers PINP (r?=??0.10, p?=?0.014) and CTX (r?=??0.13, p?=?0.0026) and with intact PTH (r?=??0.13, p?=?0.0064). There was no significant association of serum sclerostin with 25(OH)D, estradiol, free estradiol index, or testosterone. Serum sclerostin considered as a continuous variable or in quartiles was not significantly associated with the risk of prevalent or incident fracture.

Conclusion

Serum sclerostin is weakly correlated with BMD, bone turnover, and PTH in postmenopausal women. It was not significantly associated with the risk of all fractures, although the number of incident fractures recorded may not allow detecting a modest association.     

Vitamin D Supplementation Efficacy: Sleeve Gastrectomy Versus Gastric Bypass Surgery

Background

Vitamin D deficiency is common with bariatric surgery, and few prospective studies comparing different surgical procedures have evaluated appropriate vitamin D supplementation levels. Therefore, vitamin D₃ and calcium supplementation were evaluated following gastric bypass and sleeve gastrectomy.

Methods

Women consumed 2,000 international units (IU) of vitamin D₃ and 1,500 mg calcium citrate daily for 3 months following gastric bypass (n?=?11) and sleeve gastrectomy (n?=?12). Height, weight, body mass index (BMI), serum 25-hydroxyvitamin D [25(OH)D], and serum PTH concentrations were measured preoperatively and at 3 months. Wilcoxon signed rank analyses compared body weight parameters, serum 25(OH)D and PTH concentrations, and dietary intakes of vitamin D and calcium preoperatively and at 3 months. Vitamin D deficiency was defined as a serum 25(OH)D concentration <20 ng/mL (50 nmol/L).

Results

Vitamin D deficiency decreased from 60.6 % preoperatively to 26.1 % after 3 months (P?P?Conclusions Reduced food intake increased the risk of vitamin D deficiency following bariatric surgery. However, daily supplementation with 2,000 IU of vitamin D₃ and 1,500 mg calcium citrate significantly increased 25(OH)D concentrations and reduced the percent of women who were vitamin D deficient. Although serum 25(OH)D concentrations did not reach levels associated with detrimental health effects, several women remained vitamin D deficient and more aggressive supplementation may be indicated.     

Effect of Bariatric Surgery on Bone Mineral Density: Comparison of Gastric Bypass and Sleeve Gastrectomy

The aim of our study was to compare bone mineral density (BMD) a year after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in age- and body mass index-matched women. In 33 morbidly obese women undergoing RYGB and 33 undergoing SG, plasma determinations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH) D₃), and insulin-like growth factor-I (IGF-I) were made prior to and at 12 months after surgery. Dual-energy X-ray absorptiometry was performed in all patients 1 year after surgery. BMD at the femoral neck and the lumbar spine 1 year after surgery was similar in women undergoing RYGB and SG (1.01?±?0.116 vs. 1.01?±?0.122 g/cm², p?=?0.993; 1.05?±?0.116 vs. 1.08?±?0.123 g/cm², p?=?0.384). The percentage of patients with osteopenia and osteoporosis was not different between groups. In the linear regression analysis, age (β?=??0.628, p?=?0.034) and lean mass 12 months after surgery (β?=?0.424, p?=?0.021) were found to be the main determinants of femoral neck BMD. Age (β?=??0.765, p?=?0.025), menopause (β?=??0.898, p?=?0.033), and lean mass (β?=?0.615, p?=?0.023) were determinants of BMD at the lumbar spine. No influence was found between low bone mass and type of surgery, plasma PTH, 25(OH) D₃, or IGF-I. The effect of RYGB and SG on BMD was comparable a year after surgery. Menopausal women were at a higher risk of having low bone mass, but the presence of osteoporosis was uncommon.     

Vitamin D levels in post-menopausal Korean women with a distal radius fracture

IntroductionThe purpose of this study was to investigate serum levels of vitamin D in post-menopausal Korean women with a distal radius fracture (DRF) and to determine if there is any association between vitamin D levels and bone-related variables such as bone mineral densities (BMDs), serum parathyroid hormone (PTH) levels and several bone turnover markers.Materials and methodsThe data of 104 postmenopausal women surgically treated for a distal radius fracture (DRF group) and 107 age-matched control patients without a fracture (control group) were compared. Serum vitamin D levels (25-hydroxycholecalciferol, 25(OH)D₃) were compared between the groups with consideration of age and seasonal variations. BMDs, serum PTH and several bone turnover markers, including serum osteocalcin, C-telopeptide and urine N-telopeptide, were measured and analysed to find any association with vitamin D levels.ResultsThe mean 25(OH)D₃ level was significantly lower in the DRF group compared to the control group (p < 0.001). In particular, patients in their sixth and seventh deciles in the DRF group had significantly lower 25(OH)D₃ levels than patients in the control group (p = 0.001 and 0.013, respectively). When seasonal variation was considered, significant differences of 25(OH)D₃ levels were found between the groups in autumn and winter. Hip BMDs were significantly lower in the DRF group than in the control group, and there was a positive correlation between serum 25(OH)D₃ levels and hip BMDs. Bone turnover markers were not significantly different between the two groups, although serum PTH levels were marginally higher in the DRF group (p = 0.08).ConclusionsPost-menopausal Korean women with a DRF were found to have significantly lower serum vitamin D levels than the control group, and vitamin D levels were particularly lower in women in their sixth and seventh deciles who may be a good target group for prevention of future fractures. Future investigation should focus on determining whether vitamin D supplementation can be helpful in preventing future fractures in patients with a DRF.     

Vitamin D Status and Bone Mineral Density Changes During Alendronate Treatment in Postmenopausal Osteoporosis

Vitamin D supplementation is recommended for women with osteoporosis. In the FOCUS-D trial comparing the combination tablet alendronate plus vitamin D₃ 5,600 IU (ALN/D) with standard care (SC) prescribed by patients’ personal physicians, ALN/D was more effective in improving serum 25(OH)D and bone turnover markers by 6 months and increasing spine and hip bone mineral density (BMD) after 1 year than SC. This post hoc analysis examined the relationship between BMD gain and 25(OH)D in women in SC receiving alendronate (SC/ALN, n = 134, 52 % of the SC group) and in the ALN/D group (n = 257). At baseline, participants were of mean age 73 years and 72 % were Caucasian, with a mean 25(OH)D of 14.9 ng/mL. In the SC/ALN group, most received vitamin D, although intake of vitamin D varied extensively (51 % received <400 μg/day). In this group, end-of-study 25(OH)D correlated positively with mean percent increases from baseline in lumbar spine and femoral neck BMD [Pearson correlation coefficients (95 % CI) = 0.23 (0.02–0.41) and 0.24 (0.03–0.41), respectively]. Baseline 25(OH)D correlated with increases in only lumbar spine BMD [Pearson correlation coefficient (95 % CI) = 0.22 (0.01–0.40)]. No correlations between mean BMD change and 25(OH)D were seen with ALN/D. In conclusion, in postmenopausal women with osteoporosis and low 25(OH)D receiving alendronate and a wide range of vitamin D doses, the increase in lumbar spine and femoral neck BMD was positively correlated with serum 25(OH)D achieved by the end of the study and, to some extent, with 25(OH)D concentrations at baseline. The degree of success of alendronate therapy for osteoporosis may depend on the vitamin D status of patients.