Higher serum 25-hydroxyvitamin D 25(OH)D concentrations have been associated with a lower risk of multiple cancer types across a range of 25(OH)D concentrations.
To investigate whether the previously ...reported inverse association between 25(OH)D and cancer risk could be replicated, and if a 25(OH)D response region could be identified among women aged 55 years and older across a broad range of 25(OH)D concentrations.
Data from two cohorts representing different median 25(OH)D concentrations were pooled to afford a broader range of 25(OH)D concentrations than either cohort alone: the Lappe cohort (N = 1,169), a randomized clinical trial cohort (median 25(OH)D = 30 ng/ml) and the GrassrootsHealth cohort (N = 1,135), a prospective cohort (median 25(OH)D = 48 ng/ml). Cancer incidence over a multi-year period (median: 3.9 years) was compared according to 25(OH)D concentration. Kaplan-Meier plots were developed and the association between 25(OH)D and cancer risk was examined with multivariate Cox regression using multiple 25(OH)D measurements and spline functions. The study included all invasive cancers excluding skin cancer.
Age-adjusted cancer incidence across the combined cohort (N = 2,304) was 840 cases per 100,000 person-years (1,020 per 100,000 person-years in the Lappe cohort and 722 per 100,000 person-years in the GrassrootsHealth cohort). Incidence was lower at higher concentrations of 25(OH)D. Women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer than women with concentrations <20 ng/ml (HR = 0.33, 95% CI = 0.12-0.90).
25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined.
Introduction: Stress fractures (SFx) are one of the most common and debilitating overuse injuries seen in military recruits, and they are also problematic for nonmilitary athletic populations. The ...goal of this randomized double‐blind, placebo‐controlled study was to determine whether a calcium and vitamin D intervention could reduce the incidence of SFx in female recruits during basic training.
Materials and Methods: We recruited 5201 female Navy recruit volunteers and randomized them to 2000 mg calcium and 800 IU vitamin D/d or placebo. SFx were ascertained when recruits reported to the Great Lakes clinic with symptoms. All SFx were confirmed with radiography or technetium scan according to the usual Navy protocol.
Results: A total of 309 subjects were diagnosed with a SFx resulting in an incidence of 5.9% per 8 wk. Using intention‐to‐treat analysis by including all enrolled subjects, we found that the calcium and vitamin D group had a 20% lower incidence of SFx than the control group (5.3% versus 6.6%, respectively, p = 0.0026 for Fisher's exact test). The per protocol analysis, including only the 3700 recruits who completed the study, found a 21% lower incidence of fractures in the supplemented versus the control group (6.8% versus 8.6%, respectively, p = 0.02 for Fisher's exact test).
Conclusions: Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment, calcium and vitamin D supplementation for the entire cohort would have prevented ∼187 persons from fracturing. Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs.
Osteoporosis mainly occurs in postmenopausal women, which is characterized by low bone mineral density (BMD) due to unbalanced bone resorption by osteoclasts and formation by osteoblasts. Circulating ...monocytes play important roles in osteoclastogenesis by acting as osteoclast precursors and secreting osteoclastogenic factors, such as IL-1, IL-6 and TNF-α. MicroRNAs (miRNAs) have been implicated as important biomarkers in various diseases. The present study aimed to find significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.
We used ABI TaqMan® miRNA array followed by qRT-PCR validation in circulating monocytes to identify miRNA biomarkers in 10 high and 10 low BMD postmenopausal Caucasian women. MiR-133a was upregulated (P=0.007) in the low compared with the high BMD groups in the array analyses, which was also validated by qRT-PCR (P=0.044). We performed bioinformatic target gene analysis and found three potential osteoclast-related target genes, CXCL11, CXCR3 and SLC39A1. In addition, we performed Pearson correlation analyses between the expression levels of miR-133a and the three potential target genes in the 20 postmenopausal women. We did find negative correlations between miR-133a and all the three genes though not significant.
This is the first in vivo miRNA expression analysis in human circulating monocytes to identify novel miRNA biomarkers underlying postmenopausal osteoporosis. Our results suggest that miR-133a in circulating monocytes is a potential biomarker for postmenopausal osteoporosis.
MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various ...diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.
We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression.
Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.
Context:
Deficits in bone acquisition during growth may increase fracture risk. Assessment of bone health during childhood requires appropriate reference values relative to age, sex, and population ...ancestry to identify bone deficits.
Objective:
The objective of this study was to provide revised and extended reference curves for bone mineral content (BMC) and areal bone mineral density (aBMD) in children.
Design:
The Bone Mineral Density in Childhood Study was a multicenter longitudinal study with annual assessments for up to 7 yr.
Setting:
The study was conducted at five clinical centers in the United States.
Participants:
Two thousand fourteen healthy children (992 males, 22% African-Americans) aged 5–23 yr participated in the study.
Intervention:
There were no interventions.
Main Outcome Measures:
Reference percentiles for BMC and aBMD of the total body, lumbar spine, hip, and forearm were obtained using dual-energy x-ray absorptiometry for Black and non-Black children. Adjustment factors for height status were also calculated.
Results:
Extended reference curves for BMC and aBMD of the total body, total body less head, lumbar spine, total hip, femoral neck, and forearm for ages 5–20 yr were constructed relative to sex and age for Black and non-Black children. Curves are similar to those previously published for 7–17 year olds. BMC and aBMD values were greater for Black vs. non-Black children at all measurement sites.
Conclusions:
We provide here dual-energy x-ray absorptiometry reference data on a well-characterized cohort of 2012 children and adolescents. These reference curves provide the most robust reference values for the assessment and monitoring of bone health in children and adolescents in the literature to date.
While numerous epidemiologic studies have found an association between higher serum 25-hydroxyvitamin D 25(OH)D concentrations and lower breast cancer risk, few have assessed this association for ...concentrations >40 ng/ml.
To investigate the relationship between 25(OH)D concentration and breast cancer risk across a broad range of 25(OH)D concentrations among women aged 55 years and older.
Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from <20 to ≥60 ng/ml (<50 to ≥150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements.
Within the pooled cohort (N = 5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses. First, comparing incidence rates, there was an 82% lower incidence rate of breast cancer for women with 25(OH)D concentrations ≥60 vs <20 ng/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20-39, 40-59 and ≥60 ng/ml were significantly different (P = 0.02), with the highest proportion breast cancer-free in the ≥60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 vs <20 ng/ml (P = 0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations ≥60 ng/ml had an 80% lower risk of breast cancer than women with concentrations <20 ng/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin.
Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ≥60 ng/ml being most protective.
Vitamin D, cardiovascular disease and mortality Pilz, Stefan; Tomaschitz, Andreas; März, Winfried ...
Clinical endocrinology (Oxford),
November 2011, 2011-Nov, 20111101, 2011-11, Letnik:
75, Številka:
5
Journal Article, Web Resource
Recenzirano
Odprti dostop
Summary
A poor vitamin D status, i.e. low serum levels of 25‐hydroxyvitamin D 25(OH)D, is common in the general population. This finding is of concern not only because of the classic vitamin D ...effects on musculoskeletal outcomes, but also because expression of the vitamin D receptor (VDR) and vitamin D metabolizing enzymes in the heart and blood vessels suggests a role of vitamin D in the cardiovascular system. VDR‐knockout mice suffer from cardiovascular disease (CVD), and various experimental studies suggest cardiovascular protection by vitamin D, including antiatherosclerotic, anti‐inflammatory and direct cardio‐protective actions, beneficial effects on classic cardiovascular risk factors as well as suppression of parathyroid hormone (PTH) levels. In epidemiological studies, low levels of 25(OH)D are associated with increased risk of CVD and mortality. Data from randomized controlled trials (RCTs) are sparse and have partially, but not consistently, shown some beneficial effects of vitamin D supplementation on cardiovascular risk factors (e.g. arterial hypertension). We have insufficient data on vitamin D effects on cardiovascular events, but meta‐analyses of RCTs indicate that vitamin D may modestly reduce all‐cause mortality. Despite accumulating data suggesting that a sufficient vitamin D status may protect against CVD, we still must wait for results of large‐scale RCTs before raising general recommendations for vitamin D in the prevention and treatment of CVD. In current clinical practice, the overall risks and costs of vitamin D supplementation should be weighed against the potential adverse consequences of untreated vitamin D deficiency.
We previously reported that sequential teriparatide followed by denosumab substantially increases BMD in premenopausal idiopathic osteoporosis (PremenIOP).
To determine whether administration of ...bisphosphonates after denosumab cessation is associated with stable BMD in PremenIOP.
Open-label extension study.
24 PremenIOP Teriparatide-Denosumab Study participants.
Oral alendronate (ALN), 70mg weekly, or IV zoledronic acid (ZOL), 5mg once (patient choice), was administered 7 months (M) after final denosumab dose.
BMD by DXA and serum C-telopeptide (CTX) q6M; vertebral fracture assessment (VFA) and HR-pQCT q12M.
24 women with PremenIOP (aged 43 ± 8 years), severely affected with low trauma adult fractures (range 0-12; 9 with vertebral fractures) and/or very low BMD, had large BMD increases on sequential teriparatide-denosumab (spine: 25 ± 9%; total hip: 11 ± 6%). During the Bisphosphonate Extension, mean BMD and CTX changes in the entire group were small and not statistically significant at 6 or 12M.Women choosing ZOL (n = 6) versus ALN (n = 18) did not differ by baseline age, BMI, fractures, BMD, or CTX. On ZOL, there were small LSBMD declines and CTX increases, particularly between 6M and 12M, while greater stability was observed on ALN.Changes in BMD and CTX did not differ by duration of denosumab (36M vs <36M) or between 20 women who remained premenopausal and 4 who transitioned into menopause. Higher pre-teriparatide CTX, likely reflecting baseline remodeling status, predicted more spine and hip bone loss. No new vertebral (clinical or VFA screening) or non-vertebral fractures occurred.
BMD remained stable in women with PremenIOP who received bisphosphonates after sequential teriparatide-denosumab therapy.
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