Calcaneal quantitative ultrasound is associated with all-cause and cardiovascular disease mortality independent of hip bone mineral density.

Osteoporosis has been linked with increased risk of cardiovascular disease previously. However, few studies have detailed bone and vascular information. In a prospective study of older women, we demonstrated heel quantitative ultrasound measures were associated with increased cardiovascular and all-cause mortality, independent of established cardiovascular risk factors. INTRODUCTION: Osteoporosis and low bone mineral density (BMD) have been previously linked to cardiovascular disease (CVD) and mortality. Calcaneal quantitative ultrasound (QUS) is used to evaluate bone material properties, especially in older women. However, it is uncertain whether it is related to risk of mortality. This study was aimed to investigate the association between calcaneal QUS measurements and 15-year all-cause and CVD mortality in 1404 older women (mean age 75.2 ± 2.7 years). METHODS: One thousand four hundred four older women, participants of Calcium Intake Fracture Outcome study (CAIFOS), had calcaneal bone measured at baseline (1998) and followed for 15 years. The primary outcomes, any deaths, and deaths attributable to cardiovascular causes ascertained by using linked data were obtained from Western Australia data linkage system. RESULTS: Over the 15 years of follow-up (17,955 person years), 584 of the women died, and 223 from CVD. For every standard deviation (SD), reduction in broadband ultrasound attenuation (BUA) in minimally and multivariable-adjusted model including cardiovascular risk factors increased relative hazards for all-cause (multivariable-adjusted HR 1.15; 95%CI: 1.06-1.26, p = 0.001) and CVD mortality (multivariable-adjusted HR 1.20; 95%CI: 1.04-1.38, p = 0.010). Such relationships also persisted when hip BMD was included in the model (all-cause mortality HR 1.19; 95%CI: 1.07-1.33, p = 0.002; CVD mortality HR 1.28; 95%CI: 1.07-1.53, p = 0.008). CONCLUSION: BUA is associated with all-cause and CVD mortality in older women independent of BMD and established CVD risk factors. Understanding why and how these are related may provide further insights about the bone-vascular nexus as well as therapeutic targets benefiting both systems.

Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years.

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0-4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2 = 32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed) = 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD(fixed) = 0.04 g/cm2 (0.00 to 0.08, P = 0.07), I2 = 0%) or FNBMD (total n = 435, MD(random) = 0.01 g/cm2 (-0.03 to 0.05, P = 0.59), I2 = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

Utility of four sarcopenia criteria for the prediction of falls-related hospitalization in older Australian women.

Numerous sarcopenia definitions are not associated with increased falls-related hospitalization risk over 5 years to 9.5 years in older community-dwelling Australian women. Measures of muscle strength and physical function, but not appendicular lean mass (measured by dual-energy X-ray absorptiometry) may help discriminate the risk of falls-related hospitalization. INTRODUCTION: The aim of this prospective, population-based cohort study of 903 Caucasian-Australian women (mean age 79.9 ± 2.6 years) was to compare the clinical utility of four sarcopenia definitions for the prediction of falls-related hospitalization over 9.5 years. METHODS: The four definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and modified FNIH (AUS-POPF) and EWGSOP (AUS-POPE) definitions using Australian population-specific cut points (< 2 SD below the mean of young healthy Australian women). Components of sarcopenia including muscle strength, physical function, and appendicular lean mass (ALM) were quantified using hand grip strength, timed-up-and-go (TUG), and dual-energy X-ray absorptiometry (DXA), respectively. Incident 9.5-year falls-related hospitalization were captured by linked data. RESULTS: Baseline prevalence of sarcopenia according to FNIH (9.4%), EWGSOP (24.1%), AUS-POPF (12.0%), and AUS-POPE (10.7%) differed substantially. Sarcopenia did not increase the relative hazard ratio (HR) for falls-related hospitalization before or after adjustment for age (aHR): FNIH aHR 1.00 95%CI (0.69-1.47), EWGSOP aHR 1.20 95%CI (0.93-1.54), AUS-POPF aHR 0.96 95%CI (0.68-1.35), and AUS-POPE aHR 1.33 95%CI (0.94-1.88). When examining individual components of sarcopenia, only muscle strength and physical function but not ALM (adjusted for height2 or BMI) were associated with falls-related hospitalization. CONCLUSION: Current definitions of sarcopenia were not associated with falls-related hospitalization risk in this cohort of community-dwelling older Australian women. Finally, measures of muscle strength and physical function, but not ALM (measured by DXA) may help discriminate the risk of falls-related hospitalization.

Effects of calcium supplementation on circulating osteocalcin and glycated haemoglobin in older women.

One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control. INTRODUCTION: Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years). METHODS: Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998-2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999). RESULTS: After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 µg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 µg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels. CONCLUSION: One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.

Ageing Effects on 3-Dimensional Femoral Neck Cross-Sectional Asymmetry: Implications for Age-Related Bone Fragility in Falling.

This paper explores the effects of aging on femoral neck (FN) anatomy in a study of women aged 20-90years in relation to implications for FN fracture propensity in buckling. Five hundred and four participants were scanned by Quantitative Computed Tomography and analyzed using Quantitative Computed Tomography Pro BIT (Mindways). FN cross-section was split through geometric center into superior and inferior sectors. Bone mass, structural measurements, and bone mineral density were analyzed. Buckling ratio was calculated as ratio of buckling radius to cortical thickness. Between 2nd decade and 8th decade, age-related integral bone mass reduction in superior sector was substantially larger than in inferior sector (33% compared to 21%), especially in cortical bone superiorly compared to inferiorly (53% vs 21%; p < 0.001), principally due to reduction in cortical thickness, averaged cortical thickness (56%) with little difference in density. Superior and inferior sector trabecular bone mineral density reduction was similar at 41% and 43% respectively. Differential cortical bone loss in superior sector resulted in a 59% inferior displacement (δ) of center-of-mass from geometric center. Differences in δ and averaged cortical thickness with age accounted for a 151% increase in mean superior buckling ratio from 9 to 23. Analysis confirms significant progressive age-related superior cortical bone loss as the major age effect on FN structure with relative preservation of inferior cortex probably related to maintenance of inferior sector by regular loading as a result of standing and walking. Computation of buckling ratio may allow prediction of fracture propensity in a sideways fall.

Evaluation of a simplified hip structure analysis method for the prediction of incident hip fracture events.

UNLABELLED: Many attempts have been made to improve the predictive ability of areal bone mineral density (aBMD) which integrates bone mass and area. The addition of an extra variable derived from the hip dual-energy X-ray (DXA) image TR_σ, which describes distribution of mass within the scanned area of the trochanter, improved prediction of 15-year hip fracture probability in elderly women. INTRODUCTION: Two-dimensional DXA imaging of the proximal femur to produce an aBMD is a clinically useful predictor of future fracture risk. Further analysis of the DXA image to produce an eight-variable hip structure analysis (Beck HSA) has been developed to improve understanding of structural factors determining hip bone strength at each of three proximal femur sites, the narrow femoral neck (NN), intertrochanter (TR) and shaft (S). Recently, data on four measurements derived from the currently used eight Beck HSA variables were used to capture population variation in bone structure at each site. These include two previously used variables, the localised aBMD and the sub-periosteal width (W) applying to 5-mm sections (at each sites), and two new variables, standard deviation of normalised mineral-mass projection profile distribution (σ), and displacement between centre-of-mineral mass and geometric centre-of-mineral mass of projection profile (δ). METHODS: Using a cohort of 1159 women, mean baseline age 75, who sustained 139 hip fractures over 15 years, we determined whether these measures significantly improved 15-year hip fracture prediction compared to current approach utilising age and total hip aBMD. To describe the most parsimonious model for hip fracture risk prediction, the 12 base measures (4 from each site), total hip aBMD and age were evaluated in stepwise logistic regression models. RESULTS: The final model included TR_σ, total hip aBMD and age and provided improved utility for hip fracture prediction compared to total hip aBMD and age alone (C-statistic 0.73 vs. 0.69, P = 0.009 and net reclassification improvement 0.164, P < 0.001, respectively). CONCLUSIONS: Addition of TR_σ to total hip aBMD and age substantially improved prediction of 15-year hip fracture risk in this cohort of elderly women.

The effect of yoghurt and its probiotics on blood pressure and serum lipid profile; a randomised controlled trial.

BACKGROUND AND AIMS: Despite strong mechanistic data, and promising results from in vitro and animal studies, the ability of probiotic bacteria to improve blood pressure and serum lipid concentrations in humans remains uncertain. The aim of this study was to determine the effect of Lactobacillus acidophilus La5 and Bifidobacterium animalis subsp lactis Bb12, provided in either yoghurt or capsule form, on home blood pressure and serum lipid profile. METHODS AND RESULTS: Following a 3-week washout period, 156 overweight men and women over 55 y were randomized to a 6-week double-blinded, factorial, parallel study. The four intervention groups were: A) probiotic yoghurt plus probiotic capsules; B) probiotic yoghurt plus placebo capsules; C) control milk plus probiotic capsules; and D) control milk plus placebo capsules. Each probiotic test article provided a minimum L. acidophilus La5 and B. animalis subsp. lactis Bb12 dose of 3.0 × 109 CFU/d. Home blood pressure monitoring, consisting of 7-day bi-daily repeat measurements, were collected at baseline and week 6. Fasting total cholesterol, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and serum triglyceride were performed at baseline and week 6. When compared to control milk, probiotic yoghurt did not significantly alter blood pressure, heart rate or serum lipid concentrations (P > 0.05). Similarly, when compared to placebo capsules, supplementation with probiotic capsules did not alter blood pressure or concentrations of total cholesterol LDLC, HDLC, or triglycerides (P > 0.05). CONCLUSIONS: The probiotic strains L. acidophilus La5 and B. animalis subsp. lactis Bb12 did not improve cardiovascular risk factors.

Consumption of a whey protein-enriched diet may prevent hepatic steatosis associated with weight gain in elderly women.

BACKGROUND AND AIMS: Protein consumption has been associated with cardio-metabolic benefits, including weight loss and improved insulin sensitivity, and may have potential benefits for individuals with fatty liver disease (FLD). We investigated the effect of increasing dietary protein intake from whey relative to carbohydrate on hepatic steatosis. METHODS AND RESULTS: A two-year randomized, double-blind, placebo-controlled trial of 30 g/day whey protein-supplemented beverage (protein) or an energy-matched low-protein high-carbohydrate beverage (control) for cardio-metabolic and bone health in 219 healthy elderly women, recruited from the Western Australian general population. Hepatic steatosis was quantified using computed tomographic liver-to-spleen (L/S) ratio. FLD was defined as liver-to-spleen difference <10 Hounsfield units. At baseline, FLD prevalence was 11.4%. Control and protein groups were similar in body mass index (BMI), insulin resistance, L/S ratio and FLD prevalence at baseline. At two-years, dietary protein increased by 20 g in the protein, but not the control, group. Total energy intake and physical activity remained similar between groups. At two-years, BMI and FLD prevalence increased in both groups, with no between group differences. L/S ratio increased in control, but not protein, group at two-years, with no between group differences. In a within group comparison, change in BMI correlated with changes in L/S ratio in control (r = 0.37, P = 0.0007), but not with protein group (r = 0.04, P = 0.73). CONCLUSION: Increasing dietary protein intake from whey relative to carbohydrate does not reduce weight, hepatic steatosis or the prevalence of FLD in elderly women. However, it may prevent worsening of hepatic steatosis associated with weight gain. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (Registration no. ACTRN012607000163404).

Higher Dietary Vitamin K Intake is Associated with Better Physical Function and Lower Long-Term Injurious Falls Risk in Community-Dwelling Older Women.

BACKGROUND: In recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support muscle function in the context of falls prevention remains unknown. OBJECTIVE: To examine the relationship of dietary Vitamin K1 and K2 with muscle function and long-term injurious fall-related hospitalisations in older women. DESIGN: Cohort study. PARTICIPANTS: 1347 community-dwelling older Australian women ≥70 years. MEASUREMENTS: A new Australian Vitamin K nutrient database, supplemented with published data, was used to calculate Vitamin K1 and K2 intake from a validated food frequency questionnaire at baseline (1998). Muscle function (grip strength and timed-up-and-go; TUG) as well plasma Vitamin D status (25OHD) were also assessed at baseline. Fall-related hospitalisations over 14.5 years were obtained from linked health records. Multivariable-adjusted logistic regression and Cox-proportional hazard models were used to analyse the data. RESULTS: Over 14.5 years of follow-up (14,774 person-years), 535 (39.7%) women experienced a fall-related hospitalisation. Compared to women with the lowest Vitamin K1 intake (Quartile 1, median 49 µg/d), those with the highest intake (Quartile 4, median 120 µg/d) had 29% lower odds (OR 0.71 95%CI 0.52-0.97) for slow TUG performance (>10.2 s), and 26% lower relative hazards of a fall-related hospitalisation (HR 0.74 95%CI 0.59-0.93) after multivariable adjustment. These associations were non-linear and plateaued at moderate intakes of ~70-100 µg/d. There was no relation to grip strength. Vitamin K2 intakes were not associated with muscle function or falls. CONCLUSION: A higher habitual Vitamin K1 intake was associated with better physical function and lower long-term injurious falls risk in community-dwelling older women. In the context of musculoskeletal health, Vitamin K1 found abundantly in green leafy vegetables should be promoted.

An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT.

SUMMARY: In a population of elderly women, bone cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), femoral neck axis length (FNAL), and width measured with hip structure analysis (HSA) on dual-energy x-ray absorptiometry (DXA) images in the femoral neck and trochanteric regions are highly correlated to quantitative computed tomography (QCT) measurements. INTRODUCTION: HSA is a method of obtaining measurements of proximal femur structure using 2D DXA technology. This study was designed to examine the correlations between HSA measurements and 3D QCT. METHODS: Forty-one women (mean age, 82.8 ± 2.5 years) were measured using DXA and a 64-slice CT scanner (1 mm slice thickness, 0.29 mm in plane resolution). HSA parameters were calculated at the narrow neck (NN) and trochanteric (IT) regions on the DXA image. These regions were then translated to anatomically equivalent regions on the QCT dataset by co-registering the DXA image and QCT dataset using four DXA images acquired at different angles. RESULTS: At the NN and IT regions, high linear correlations were measured between HSA and QCT for CSA r = 0.95 and 0.93, CSMI r = 0.94 and 0.93, and Z r = 0.93 and 0.89, respectively. All correlations were highly significant (p < 0.001), but there were differences in slope and offset between the two techniques, at least in part due to differences in calibration between the two techniques. FNAL and width of the bone at the NN and IT regions, physical measurements independent of the calibration, were highly correlated (r = 0.90-0.95, p < 0.001) and had slopes close to 1.0 (range, 0.978 to 1.003). CONCLUSION: CSA, CSMI, Z, FNAL, and width measured by HSA correlate highly to high-resolution QCT.

Differences in structural geometrical outcomes at the neck of the proximal femur using two-dimensional DXA-derived projection (APEX) and three-dimensional QCT-derived (BIT QCT) techniques.

UNLABELLED: Structural geometric parameters at neck of the proximal femur were obtained using DXA-derived hip structural analysis (APEX 3) and quantitative computed tomography-derived (BIT QCT) techniques in 237 elderly females. Linear correlations for parameters ranged from 0.45 to 0.90. The average value of the subperiosteal width, as determined by the two techniques, was the same; variables dependent on mass measurements were different. INTRODUCTION: There has been increasing interest in using bone structural geometry to assess bone fragility to complement bone mineral mass. The objective of this study is to compare structural geometrical differences between "2D" DXA-derived and "3D" QCT-derived techniques in unselected clinical cases. METHODS: All 237 females had both DXA and QCT assessments of femoral neck structural geometry. Variables compared were areal bone mineral density, cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), averaged cortical thickness (Ct), endosteal width (ESW), subperiosteal width (W), and buckling ratio (BR). RESULTS: Correlation of femoral neck variables ranged from 0.45 for ESW to 0.90 for CSA. APEX 3 and BIT QCT-derived femoral neck W values were numerically similar. However CSA, CSMI, Z and Ct values measured by APEX 3 were higher and ESW and BR values were lower than corresponding BIT QCT. CONCLUSIONS: 2D DXA structural analysis of neck of femur is related to but different from same parameters calculated from true 3D images obtained by CT. Femoral neck size values are similar for DXA and QCT, but structural geometrical variables dependent on mass calibration standards, location of neck ROI and mathematical derivation techniques are different.

Homozygous deletion of the UGT2B17 gene is not associated with osteoporosis risk in elderly Caucasian women.

UNLABELLED: Previously, homozygous deletion of the UGT2B17 gene has shown association with hip fracture. Using a high-throughput qRT-PCR assay, we genotyped UGT2B17 copy number variation (CNV) in 1,347 elderly Caucasian women and examined for effects on bone phenotypes. We found no evidence of association between UGT2B17 CNV and osteoporosis risk in this population. INTRODUCTION: Genetic studies of osteoporosis commonly examine SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called CNV, also comprise a large amount of the genetic variability between individuals. Previously, homozygous deletion of the UGT2B17 gene in CNV 4q13.2, which encodes an enzyme that mediates the glucuronidation of steroid hormones, has shown association with the risk of hip fracture. METHODS: We used a quantitative real-time PCR assay for genotyping the UGT2B17 CNV in a well-characterized population study of 1,347 Caucasian women aged 75.2 ± 2.7 years (mean ± SD), to assess the effect of the CNV on bone mass density (BMD) at the total hip site and osteoporosis risk. RESULTS: The UGT2B17 CNV distribution was consistent with the expected Hardy-Weinberg distribution and not different from frequencies previously reported in a Caucasian population. Data from ANCOVA of age- and weight-adjusted BMD for UGT2B17 CNV genotype showed no significant difference between genotype groups. Individuals with homozygous or heterozygous deletion of the UGT2B17 gene showed no increased risk of incident fragility fracture. CONCLUSIONS: These data suggest that quantitative real-time PCR is a rapid and efficient technique for determination of candidate CNVs, including the UGT2B17 CNV; however, we found no evidence of an effect of UGT2B17 CNV on osteoporosis risk in elderly Caucasian women.

The calcium scare--what would Austin Bradford Hill have thought?

UNLABELLED: Detailed consideration of the suggested association between calcium supplementation and heart attacks has revealed weakness in the evidence which make the hypothesis highly implausible. INTRODUCTION: The aim of this study was to evaluate the strength of the evidence that calcium supplementation increases the risk of myocardial infarction. METHODS: This study used critical examination of a meta-analysis of the effects of calcium supplements on heart attacks in five prospective trials on 8,016 men and women, and consideration of related publications by the same author. RESULTS: The meta-analysis was found to be subject to several limitations including non-adherence to the clinical protocol, multiple endpoint testing and failure to correctly adjust for endpoint ascertainment. The main risk factors for myocardial infarction were not available for 65% of the participants, and none of the trials had cardiovascular disease as its primary endpoint. There were more overweight participants, more subjects on thyroxine and more men on calcium than on placebo. In particular, over 65% of all the heart attacks were self-reported. When the evidence was considered in the light of Austin Bradford Hill's six main criteria for disease causation, it was found not to be biologically plausible or strong or to reflect a dose-response relationship or to be consistent or to reflect the relationship between the trends in calcium supplementation and heart attacks in the community or to have been confirmed by experiment. The addition of a more recent trial on 1,460 women over 5 years reduced the relative risk to 1.23 (P = 0.0695). CONCLUSION: Present evidence that calcium supplementation increases heart attacks is too weak to justify a change in prescribing habits.

Significant association between common polymorphisms in the aromatase gene CYP19A1 and bone mineral density in postmenopausal women.

17ß-Estradiol is important in maintaining bone structure, and regulation of its synthesis plays an important role in the development of postmenopausal osteoporosis. We and others have demonstrated associations between variation in the CYP19A1 gene (encoding aromatase) and areal bone mineral density (aBMD) phenotypes in women. In the present study 33 tag polymorphisms were genotyped across the CYP19A1 gene in a population of 1,185 Caucasian postmenopausal women to test the association between sequence variations, total DXA hip aBMD, and circulating 17ß-estradiol levels. An in silico bioinformatics analysis was performed for single nucleotide polymorphisms (SNPs) associated with aBMD to identify putative functional effects, while linkage disequilibrium analysis of these SNPs was undertaken with previously published sequence variants. Five SNPs located in the central third of the gene were strongly associated with total-hip aBMD after adjustment for age (P = 0.006-0.013). A haplotype analysis of these five SNPs revealed an association between the haplotype C-G-G-G-C and increased aBMD (P = 0.008) and the haplotype A-A-A-A-A and a decreased aBMD (P = 0.021). The haplotype frequency was 9.0% for C-G-G-G-C and 15.4% for A-A-A-A-A, with the variation in mean total-hip aBMD explained by the haplotype analyses being 5% and 7%, respectively. None of these polymorphisms was significantly associated with circulating 17ß-estradiol levels. In conclusion, common genetic variations within the CYP19A1 gene are significantly associated with aBMD in postmenopausal Caucasian women.

Effects of a 1-year randomized controlled trial of resistance training on lower limb bone and muscle structure and function in older men.

SUMMARY: A 1-year randomized controlled trial of resistance training compared with a control group was undertaken in 143 men aged 55-80 years. Although hip bone mineral density, lean body mass, and function increased in both groups, lean body mass and function but not bone density increased more in the resistance group. INTRODUCTION: Previous studies have demonstrated a positive effect of resistance training on bone mineral density (BMD) in postmenopausal women, but the effect in men is unclear. The aim was to examine the effect of a 1-year resistance training program on bone and lean body mass in 143 men aged 55-80 years, randomized to either resistance training or active control. METHODS: Resistance exercises were selected to provide loading at the hips. Measurements were taken at 0, 6, and 12 months for BMD (whole body, hip, and spine), lean body mass, strength, and functional fitness. RESULTS: The intervention showed a significant increase in total hip BMD for both groups at 12 months (active control, 1,014-1,050 mg/cm(2); resistance, 1,045-1,054 mg/cm(2), p < 0.05) with no increased effect of resistance training compared to active control. However, compared to the active control group, the resistance group increased their lean body mass (active control, 0.1 +/- 2.1%; resistance, 1.5 +/- 2.7%, p < 0.05), fitness (active control, 4.6 +/- 11.1%; resistance, 13.0 +/- 13.4%, p < 0.05), and lower limb muscle strength (active control, 14.3 +/- 16.8%; resistance, 39.4 +/- 30.87%, p < 0.05). CONCLUSIONS: In contrast to previous findings in older women, in older men, a resistance training program does not increase hip bone mass more than walking 30 min three times a week.

The effects of high potassium consumption on bone mineral density in a prospective cohort study of elderly postmenopausal women.

UNLABELLED: Few studies have investigated the long-term effects of potassium intake on BMD. In a cohort of 266 elderly women, we found that baseline potassium intake as reflected by 24-hour urine potassium excretion had positive association with BMD measured at 1 and/or 5 years later, suggesting a role of dietary potassium on osteoporosis prevention. INTRODUCTION: High dietary potassium intake has been suggested to be beneficial for bone structure, but few studies have investigated the long-term effects of potassium intake on BMD in elderly women. We examined the relationship between potassium intake as reflected by 24-hour urine potassium excretion and bone density in a cohort of elderly women. METHODS: The study subjects were 266 elderly postmenopausal women aged 70-80 years. Twenty-four-hour urinary potassium excretion was determined at baseline. At one year hip DXA BMD was measured, at 5 years hip and total body DXA BMD and distal radius and tibia pQCT vBMD were measured. The effects of potassium were evaluated by ANCOVA according to the quartile of baseline urinary potassium excretion. RESULTS: After adjustment for confounding factors, subjects in the highest quartile of urinary potassium excretion had significantly higher total hip BMD at 1 (5%) and 5 years (6%), and significantly higher total body BMD (4%) and 4% distal tibia total (7%) and trabecular vBMD (11%) at 5 years than those in the lowest quartile. CONCLUSIONS: Potassium intake shows positive association with bone density in elderly women, suggesting that increasing consumption of food rich in potassium may play a role in osteoporosis prevention.

The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women.

SUMMARY: Few studies have evaluated the effects of homocysteine and methylenetetrahydrofolate reductase (MTHFR) genotype on age-related bone loss. In our 5-year cohort study with 1,213 women aged 70-85 years, high homocysteine is associated with greater hip bone loss but not fracture risk. The effect of MTHFR genotype on bone density and fracture is weak. INTRODUCTION: Previous studies on the effects of homocysteine and MTHFR genotype on bone mineral density (BMD) and osteoporotic fracture risk have shown inconsistent results. Few studies have evaluated their effects on age-related bone loss. We evaluated the effects of homocysteine and MTHFR genotype variation on hip BMD and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70-85 years. METHODS: Nutritional intake and prevalent fracture status were assessed at baseline, plasma homocysteine was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographic report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of covariance and Cox proportional hazard regression. RESULTS: The highest tertile of homocysteine was associated with a greater hip BMD loss over 4 years (-2.8%) compared to the middle (-1.6%) and lowest tertiles (-1.2%) (P < 0.001). This effect remained after adjustment for covariates. There was no effect of homocysteine on fracture prevalence or incidence. MTHFR gene variation was only weakly related to one of the bone outcome measures. CONCLUSION: In this study population, high homocysteine is associated with greater hip bone loss but not fracture risk.

Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores.

UNLABELLED: Two-dimensional areal bone mineral density (aBMD) of the proximal femur measured by three-dimensional quantitative computed tomography (QCT) in 91 elderly women was compared to dual-energy X-ray absorptiometry (DXA) aBMD results measured in the same patients. The measurements were highly correlated, though QCT aBMD values were marginally lower in absolute units. Transformation of the QCT aBMD values to T score values using National Health and Nutrition Examination Survey (NHANES) DXA-derived reference data improved agreement and clinical utility. INTRODUCTION: World Health Organization guidelines promulgate aBMD (g cm(-2)) measurement of the proximal femur for the diagnosis of bone fragility. In recent years, there has been increasing interest in QCT to facilitate understanding of three-dimensional bone structure and strength. OBJECTIVE: To assist in comparison of QCT-derived data with DXA aBMD results, a technique for deriving aBMD from QCT measurements has been developed. METHODS: To test the validity of the QCT method, 91 elderly females were scanned on both DXA and CT scanners. QCT-derived DXA equivalent aBMD (QCT(DXA) aBMD) was calculated using CTXA Hip software (Mindways Software Inc., Austin, TX, USA) and compared to DXA-derived aBMD results. RESULTS: Test retest analysis indicated lower root mean square (RMS) errors for CTXA; F test between CTXA and DXA was significantly different at femoral neck (FN) and trochanter (TR) (p < 0.05). QCT underestimates DXA values by 0.02 +/- 0.05 g cm(-2) (total hip, TH), 0.01 +/- 0.04 g cm(-2) (FN), 0.03 +/- 0.07 g cm(-2) (inter-trochanter, IT), and 0.02 +/- 0.05 g cm(-2) (TR). The RMS errors (standard error of estimate) between QCT and DXA T scores for TH, FN, IT, and TR were 0.36, 0.40, 0.39, and 0.49, respectively. CONCLUSIONS: This study shows that results from QCT aBMD appropriately adjusted can be evaluated against NHANES reference data to diagnose osteoporosis.

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes.

AIMS: To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. METHODS: One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20-71 years underwent cross-sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x-ray absorptiometry. BMD data were available for 102 age- and gender-matched population-based control subjects. RESULTS: After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T- and Z-scores at the hip, femoral neck and spine were lower compared with age-matched control subjects (P < or = 0.048). Female Type 1 patients and control subjects had similar BMDs and T- and Z-scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. CONCLUSIONS: Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age-matched control subjects. Impaired bone formation may occur in Type 1 diabetes.

A cohort study of the effect of endogenous estrogen on spine fracture risk and bone structure in elderly women and an assessment of its diagnostic usefulness.

The decline in endogenous estrogen concentration after menopause is associated with accelerated bone loss. However, effects in older women remain controversial and the usefulness of estrogen status as a predictor of spine fracture has not been assessed. Therefore, we undertook a prospective cohort study of 1350 women mean age 75 years in order to study the role of endogenous estrogen concentration on the risk of morphometric X-ray absorptiometry (MXA)-defined vertebral deformity and atraumatic clinical spine fracture and the association of endogenous estrogen with bone structure. At 5 years 70 patients (5.2%) had sustained > or = 1 incident spine fracture. The fracture group had significantly lower concentrations of baseline free estradiol index (FEI) median (IQ range) (0.38 (0.22-0.60) vs. 0.49 (0.29-0.84) pmol/nmol, p=0.009). The patients in the lowest tertile of FEI (FEI <0.35) had twice the risk of sustaining a clinical vertebral fracture compared to those subjects in the highest tertile (FEI >0.68) (HR 2.18: 95% CI 1.11-4.28). A low FEI was associated with an increased risk of a vertebral deformity over the 5-year study (OR 1.77: 95% CI 1.02-3.07) for the lowest compared to highest tertile. A low baseline FEI was associated with lower baseline QUS heel bone structure and DXA hip bone structure at 12 months and with deterioration in QUS heel bone structure 5 years later. The effect size of the FEI in predicting spine fracture was similar to the effect size for DXA BMD and heel QUS, probably because of the beneficial effect of the FEI on bone structure. The data suggest that the estrogen effect on reducing spine fracture is at least in part due to an effect on bone structure and its measurement does not significantly improve fracture prediction.