Prospective validation of a novel visual analogue uroflowmetry score (VAUS) in 1000 men with lower urinary tract symptoms (LUTS).

INTRODUCTION AND AIMS: Family physicians are limited by lack of tools to monitor benign prostate hyperplasia. VAUS provides a cost-effective, easily administered non-invasive tool. Our primary aim was to validate VAUS correlation with uroflowmetry measured maximal flow rate (Qmax), voided volume and International Prostate Symptom Scores (IPSS) symptom scores. Secondary aim was to study how the VAUS fared at predicting poor flow (Qmax < 10 ml/s) compared to age, voided volume and IPSS. Tertiary aim was to predict the best VAUS as a cutoff for poor flow. METHODS: After IRB approval, 1000 patients were prospectively recruited. They had VAUS, uroflowmetry and IPSS performed. VAUS is a novel five-point visual analogue scoring of urine flow, with one being the weakest and five the strongest. Data were analysed using SPSS where spearman's correlation coefficient and logistic regression analysis were performed looking for significance. Receiver operating curves (ROC) curves were used to identify best VAUS cutoff. RESULTS: 1000 patients were studied with mean age of 68.99 (50-95). VAUS showed good correlation with Qmaxp < 0.001, voided volume p = 0.006 and IPSS p <0.001. On multivariate analysis both VAUS and voided volume predicted poor flow significantly with p value of<0.001 and p =0.001, respectively. On ROC analysis VAUS of 2.5 was identified as best value for predicting poor flow with p value <0.001. CONCLUSION: VAUS is a validated tool for monitoring of lower urinary tract symptoms in our patients showing significant correlation with uroflowmetry, voided volume and IPSS.

Feature tracking for assessment of diastolic function by cardiovascular magnetic resonance imaging.

AIM: To assess the agreement of cardiovascular magnetic resonance imaging (CMRI) feature-tracking (FT) parameters with echocardiography to diagnose diastolic dysfunction; to determine whether a similar parameter to mitral inflow early diastolic velocity to early diastolic tissue velocity ratio (E/e') can increase accuracy of imaging by dividing the phase contrast (PC) mitral inflow E-wave (E) with a CMRI-FT parameter; to compare the agreement between CMRI-FT and PC diastolic function assessment using echocardiography. MATERIALS AND METHODS: Patients (n=71; 43 abnormal diastolic function) undergoing both CMRI and echocardiography independently were included. Echocardiography was the reference standard. CMRI-FT analysed the short and long axis cine contours. PC images of mitral inflow, tissue velocity, pulmonary vein flow, and left atrial area were assessed. RESULTS: Using CMRI-FT, the area under the curve (AUC) for identifying diastolic dysfunction was >0.80 for radial and circumferential strain, systolic strain rate (SSR), and early diastolic strain rate (DSR). For cases with CMRI-determined left ventricular ejection fraction (LVEF) ≥50% (n=38), circumferential DSR was the only parameter with good accuracy (AUC=0.87; cut-off 0.93/s). E/circumferential DSR ratio and longitudinal strain had high accuracy in all patients (AUC=0.88 and 0.93 respectively) and CMRI-determined LVEF ≥50% (AUC=0.81; cut-off 76.7). Circumferential DSR showed the highest agreement with echocardiography (higher than E/circumferential DSR and PC assessment) in all cases (kappa 0.75; p<0001) and cases with CMRI LVEF ≥50% (kappa 0.73; p<0.0001). CONCLUSIONS: CMRI-FT circumferential DSR showed the highest accuracy for determining diastolic dysfunction with good agreement with echocardiography. Circumferential DSR had higher accuracy than E/circumferential DSR and PC.

Validation of cardiac magnetic resonance tissue tracking in the rapid assessment of RV function: a comparative study to echocardiography.

AIM: To investigate the accuracy of cardiac magnetic resonance (CMR) tissue tracking (CMR-TT) and speckle tracking echocardiography (STE) against CMR determined right ventricular (RV) ejection fraction (RVEF) and to identify an optimal cut-off value for STE and CMR-TT to determine RVEF <45% and compare this to other conventional methods for estimating RVEF in dilated cardiomyopathy (DCM) patients. MATERIALS AND METHODS: Twenty-nine DCM patients were recruited prospectively. CMR and echocardiography were performed within 48 hours and four-chamber views were used for strain analysis. Contoured CMR short axis images provided RVEF. Intraclass correlation coefficient (ICC), bias, levels of agreement, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: CMR-TT RV free-wall longitudinal strain (FLS) and STE RV global longitudinal strain (GLS) showed the best correlation with RVEF (r=-0.68, r=-0.82, p<0.001 respectively). There was moderate correlation between echocardiography RV GLS and CMR RV FLS (r=0.64, p<0.001). CMR-TT FLS showed excellent intra-observer and interobserver reliability (ICC=0.980; ICC=0.968 respectively). STE GLS correlated better with RVEF than with peak systolic annular velocity (S'; r=0.45), tricuspid annular plane systolic excursion (TAPSE; r=0.56), and fractional area change (FAC; r=0.78). CMR-TT RV FLS had better correlation with RVEF than CMR TAPSE (r=0.69 versus 0.40). ROC analysis demonstrated the optimal cut-off value for CMR-TT RV FLS and STE GLS in detection of RVEF <45% was ≥-24.4% (area under the curve=0.87, 100% sensitivity, 66.7% specificity) and ≥-20.9% (area under the curve=0.88, 100% sensitivity, 60% specificity) respectively. CONCLUSION: CMR-TT FLS and STE GLS showed potential to provide rapid assessment of RV function and had superior correlation with RVEF compared to conventional parameters.

Pulmonary complications of cystic fibrosis.

The life expectancy of patients with cystic fibrosis (CF) has steadily increased over recent decades with a corresponding increase in the frequency of complications of the disease. Radiologists are increasingly involved with managing and identifying the pulmonary complications of CF. This article reviews the common manifestations of CF lung disease as well as updating radiologists with a number of less well-known complications of the condition. Early and accurate detection of the pulmonary effects of CF are increasingly important to prevent irreversible lung damage and give patients the greatest possibility of benefiting from the new therapies becoming available, which correct the underlying defect causing CF.

Estimating the heritability of reporting stressful life events captured by common genetic variants.

BACKGROUND: Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies. Method We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings. RESULTS: A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This 'heritability' was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10-8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R 2 = 0.08 in SLEs (p = 0.03). CONCLUSIONS: These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.

Depressive disorder moderates the effect of the FTO gene on body mass index.

There is evidence that obesity-related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to body mass index (BMI) in two independent samples of major depressive disorder (MDD) cases and controls. We analysed 88 polymorphisms in the FTO gene in a clinically ascertained sample of 2442 MDD cases and 809 controls (Radiant Study). In all, 8 of the top 10 single-nucleotide polymorphisms (SNPs) showing the strongest associations with BMI were followed-up in a population-based cohort (PsyCoLaus Study) consisting of 1292 depression cases and 1690 controls. Linear regression analyses of the FTO variants and BMI yielded 10 SNPs significantly associated with increased BMI in the depressive group but not the control group in the Radiant sample. The same pattern was found in the PsyCoLaus sample. We found a significant interaction between genotype and affected status in relation to BMI for seven SNPs in Radiant (P<0.0057), with PsyCoLaus giving supportive evidence for five SNPs (P-values between 0.03 and 0.06), which increased in significance when the data were combined in a meta-analysis. This is the first study investigating FTO and BMI within the context of MDD, and the results indicate that having a history of depression moderates the effect of FTO on BMI. This finding suggests that FTO is involved in the mechanism underlying the association between mood disorders and obesity.

Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project.

Suicidal thoughts during antidepressant treatment have been the focus of several candidate gene association studies. The aim of the present genome-wide association study was to identify additional genetic variants involved in increasing suicidal ideation during escitalopram and nortriptyline treatment. A total of 706 adult participants of European ancestry, treated for major depression with escitalopram or nortriptyline over 12 weeks in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study were genotyped with Illumina Human 610-Quad Beadchips (Illumina, San Diego, CA, USA). A total of 244 subjects experienced an increase in suicidal ideation during follow-up. The genetic marker most significantly associated with increasing suicidality (8.28 × 10(-7)) was a single-nucleotide polymorphism (SNP; rs11143230) located 30 kb downstream of a gene encoding guanine deaminase (GDA) on chromosome 9q21.13. Two suggestive drug-specific associations within KCNIP4 (Kv channel-interacting protein 4; chromosome 4p15.31) and near ELP3 (elongation protein 3 homolog; chromosome 8p21.1) were found in subjects treated with escitalopram. Suggestive drug by gene interactions for two SNPs near structural variants on chromosome 4q12, one SNP in the apolipoprotein O (APOO) gene on chromosome Xp22.11 and one on chromosome 11q24.3 were found. The most significant association within a set of 33 candidate genes was in the neurotrophic tyrosine kinase receptor type 2 (NTRK2) gene. Finally, we also found trend for an association within genes previously associated with psychiatric phenotypes indirectly linked to suicidal behavior, that is, GRIP1, NXPH1 and ANK3. The results suggest novel pathways involved in increasing suicidal ideation during antidepressant treatment and should help to target treatment to reduce the risk of this dramatic adverse event. Limited power precludes definitive conclusions and replication in larger sample is warranted.

Meta-analysis of 32 genome-wide linkage studies of schizophrenia.

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.

Continuous daily assessment of multiple sclerosis disability using remote step count monitoring.

Disability measures in multiple sclerosis (MS) rely heavily on ambulatory function, and current metrics fail to capture potentially important variability in walking behavior. We sought to determine whether remote step count monitoring using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability assessment. 99 adults with relapsing or progressive MS able to walk ≥2-min were prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit use was 97% of days. Substudy validation resulted in high interclass correlations between Fitbit, ActiGraph and manual step count tally during a 2-minute walk test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring. Over 4 weeks of continuous monitoring, daily steps were lower in progressive versus relapsing MS (mean difference 2546 steps, p < 0.01). Lower average daily step count was associated with greater disability on the Expanded Disability Status Scale (EDSS) (p < 0.001). Within each EDSS category, substantial variability in step count was apparent (i.e., EDSS = 6.0 range 1097-7152). Step count demonstrated moderate-strong correlations with other walking measures. Lower average daily step count is associated with greater MS disability and captures important variability in real-world walking activity otherwise masked by standard disability scales, including the EDSS. These results support remote step count monitoring as an exploratory outcome in MS trials.

Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise healthy, unselected sibling pairs.

BACKGROUND: The FOXC2 gene on 16q24 is mutated in lymphoedema distichiasis (LD), in which varicose veins (VV) are a common feature. We hypothesised that this gene might be implicated in the development of VV in the normal population, therefore, after performing a classical twin study, we tested for linkage and association in white women. We also tested for linkage with haemorrhoids (H), as a separate venous anomaly at the same locus. METHODS: A total of 2060 complete female twin pairs aged 18-80 years from the St Thomas' Adult UK Twin registry replied to questions on VV and H as part of a broader postal survey of 6600 twins (62% response rate). Dizygotic female twin pairs were tested for linkage and association to the candidate marker D16S520 (1903 individuals genotyped), which is located about 80 kb from FOXC2. RESULTS: Casewise concordance rates were significantly higher for monozygotic than dizygotic twins for both phenotypes (VV 67% v 45%; p = 2.2x10(-6); H 68% v 59%; p = 0.01; H including during pregnancy 73% v 64%; p = 2.1x10(-4)), corresponding to additive genetic heritabilities in liability of 86% (95% confidence interval (CI) 73% to 99%) for VV and 56-61% for H (95% CI 43% to 73%). The presence of VV and H were significantly correlated. We found significant evidence of linkage to the marker for VV (MLS(ASP) = 1.37, p = 0.01; GLM(ASP/DSP) Z = 3.17 p = 0.002), but no association. Both linkage and association tests were negative for H. The combined phenotype of having VV and H did not show any evidence of linkage or association. CONCLUSION: These results demonstrate VV and H to be heritable, related conditions, and the data strongly suggest FOXC2 to be implicated in the development of VV in the general population.

Genetic and environmental determinants of bone mineral density in Chinese women.

BMD is a complex trait determined by genetic and lifestyle factors. To assess the genetic and environmental determinants of BMD in southern Chinese women, we studied a community-based cohort of 531 pre- and postmenopausal southern Chinese women and assessed the influence of 12 candidate gene loci and lifestyle risk factors on spine and hip BMD. The candidate genes studied include estrogen receptor alpha (ESR1) and beta (ESR2), calcium sensing receptor (CASR), vitamin D receptor (VDR), collagen type Ialpha1 (COLIA1), and LDL receptor-related protein 5 (LRP5). Social, medical, reproductive history, dietary habits and lifestyle factors were determined using a structured questionnaire. Single nucleotide polymorphisms (SNPs) of the COLIA1 and LRP5 gene in Chinese were determined by direct sequencing. Nucleotide (nt) -1363C/G and -1997 G/T of COLIA1, nt 266A/G, 2220C/T and 3989C/T of LRP5 gene were analyzed. Using stepwise multiple linear regression analyses, body weight was the strongest predictor for BMD in premenopausal women (n = 262), which accounted for 15.9% of the variance at the spine, 20% at femoral neck, 17.1% at trochanter, 24.3% at total hip and 10.9% at the Ward's triangle. Other significant predictors were ESR1 Ivs1-397T/C genotype (2.2% at the spine); LRP5 2220C/T genotype (1.3% at the spine, 1.6% at the trochanter); LRP5 266A/G genotype (1.1% at Ward's triangle); age at menarche (1.3% at trochanter) and age (2.0% at Ward's triangle). As for postmenopausal women (n = 269), body weight ( approximately 25% at various sites) and age (approximately 16% at femoral neck, trochanter, total hip and Ward's triangle sites) were the strongest predictors of BMD. Other significant predictors were age at menarche (4.4% at spine, 0.7% at femoral neck, 1.4% at trochanter, and 1.4% at Ward's triangle); weight bearing physical activity (2.1% at trochanter and 1% at total hip); calcium intake (1.1% at femoral neck, 0.9% at trochanter, and 1.7% at total hip) ; height (0.7% at trochanter); and ESR2 1082A/G genotype (0.8% at trochanter). We conclude that BMD at various sites and at different time span of a woman is modified by different genetic and lifestyle factors, suggesting that BMD is highly dependent on gene-environmental interactions.

Fat intake in Hong Kong Chinese children.

The people of Hong Kong are experiencing a transition in dietary practices and lifestyle that can be observed in the fat intakes of Hong Kong children as compared with those of their counterparts on mainland China. The studies described here include 1) a longitudinal and observational dietary survey beginning with a cohort of 174 newborns and concluding with 124 children at age 7 y; 2) a biochemical study of serum lipids in relation to dietary fat intake at age 7 y; 3) a chemical fatty acid analysis and comparison of duplicate meals collected from 20 Hong Kong and 20 mainland Chinese children at age 7 y; 4) a dietary assessment of 52 lactoovovegetarian children aged 4-14 y; and 5) a comparison of the growth of all subjects with US National Center for Health Statistics standards. About 30% of the total daily energy intake of Hong Kong Chinese children aged 1-7 y was contributed by fat-much more than that in the traditional Chinese diet. Growth of the children was not impaired, including that of children on the mainland and of those lactoovovegetarians in Hong Kong whose fat intakes were lower. Mean serum cholesterol of Hong Kong Chinese children at age 7 y was 4.59 mmol/L, significantly higher than that of their counterparts on the mainland, 4.16 mmol/L. Foods consumed in Hong Kong had a significantly lower ratio of 18:2 to 14:0. Nutritional deficiency was uncommon. Chinese children in Hong Kong had a dietary fat intake that was both quantitatively and qualitatively different from the traditional Chinese diet.

The prevalence of microalbuminuria among patients with type II diabetes mellitus in a primary care setting: cross-sectional study.

OBJECTIVES: To determine the prevalence of microalbuminuria among patients with type II diabetes mellitus in a primary care setting, and to study the association between various risk factors and the presence of microalbuminuria. DESIGN: Cross-sectional community-based study. SETTING: Four primary care clinics, Hong Kong. PATIENTS: All patients with type II diabetes mellitus who regularly attended the clinics between May 2002 and March 2003. MAIN OUTCOME MEASURES: Patients' demographic data, the proportion with microalbuminuria (measured using a spot urine test), and the association between this condition and risk factors for diabetic nephropathy (via correlation and multivariable logistic regression analysis). RESULTS: The mean age of the 1161 patients in the sample population was 58.0 years. The mean duration of diabetes mellitus was 5.7 years, and the mean level of glycated haemoglobin was 7.4%. A total of 13.4% of the patients had microalbuminuria. Having the condition was significantly associated with advanced age, female sex, poor glycaemic control, and coexisting hypertension in both correlation and regression analyses. No significant association with ever smoking was found. CONCLUSION: Early screening for incipient diabetic nephropathy and aggressive management of modifiable risk factors in a primary care setting may be important in optimising the renal outcome of patients with type II diabetes mellitus.

A study on SARS awareness and health-seeking behaviour - findings from a sampled population attending National Healthcare Group Polyclinics.

INTRODUCTION: The study aimed to assess the effectiveness of massive SARS public education effort on SARS awareness and the conduct of those suspected of having SARS. MATERIALS AND METHODS: Five hundred and ninety-three respondents attending the National Healthcare Group Polyclinics (NHGP) participated in the survey from 9 to 13 June 2003. Associations between awareness of SARS symptoms and (i) first action to be taken and (ii) mode of transportation used, if the respondent was suspected of having SARS, were analysed using Chi-square or Fisher's exact tests. Logistic regression was performed to adjust for relevant covariates. RESULTS: The majority (92.7%) of the respondents were aware of SARS symptoms. Television (91.6%), newspaper (65.2%) and radio (30.4%) formed the top 3 sources of information on SARS. Slightly more than half (51.6%) of those who suspect themselves of having SARS would choose to visit their primary health care doctors, while 22.7% of the respondents would go to Tan Tock Seng Hospital (TTSH). If they suspected themselves to have SARS, most (84.9%) of the 578 respondents would react appropriately by taking the SARS ambulance or driving themselves to TTSH. However, 60 respondents would nonetheless take public transport to TTSH [by taxi 8.5%, mass rapid transit (MRT) or bus 1.9%]. In particular, the retired with lower educational levels were likely to be oblivious both to the symptoms of SARS and the possible consequences of travelling by inappropriate transport. CONCLUSION: Despite more than 2 months of intensive SARS public education in Singapore, there remain important gaps in knowledge and appropriate behaviour that have to be bridged.

[A comparative study on blood cholesterol and dietary fat intake between Hong Kong and Cantonese children].

Blood cholesterol level in children aged 7 in Hong Kong (4.59mmol/L) was significantly higher than that in Jiangmen City, Guangdong Province (4.16mmol/L). Duplicate meals were collected from 20 children each in Hong Kong and Jiangmen for chemical analysis of fat intake and fatty acid profile. Results showed daily fat intake was 34.7 g for children in Jiangmen, which was about 30% lower than that in Hong Kong (47.6 g). Fatty acid profile in the diet of Jiangmen children showed a significantly higher polyunsaturated fatty acid saturated fatty acid ratio (0.81 vs 0.69) and linoleic acid/myristic acid ratio (20.73 vs 10.91) than that of Hong Kong children. It suggested dietary mode in a society with rapid developing economy and well-to-do life has changed, and it is necessary to prevent from the damage to health, especially the risk of coronary heart disease, caused by over-nutrition, as early as possible.

[Prevalence of obesity in Hong Kong children and adolescents aged 3-18 years].

A cross-sectional study on growth and development in Hong Kong children and adolescents ranging from their birth to 18 years of age was performed in 1993 and all the growth standards were constructed in the form of percentile chart. Those having a weight at one's median weight for height standard of 120% were defined as obesity. Prevalence of obesity in children and adolescents aged 3-18 was 10.08% (11.28% and 8.93% for boys and girls, respectively), which was higher than that in the inland of the country and that in Hong Kong as previously reported. Result showed there was a gradual increase in the prevalence after the age of 5, which reached a peak at the age of 11 for boys and 8 for girls.

Traumatic spinal cord injury in Hawaii.

As a prelude to continuing surveillance in Hawaii, a 2-year retrospective study (1987-1989) was conducted by the Pacific Basin Rehabilitation Research & Training Center (PBRRTC) and the Rehabilitation Hospital of the Pacific (REHAB) in order to examine the frequency and causes of traumatic spinal cord injury (SCI) at REHAB; determine similarities and differences when compared to national statistics and make recommendations for future study. Data were abstracted from patient records at REHAB. During the period of study, 59 persons were treated for SCI. Similar to the national database, 85% were males and 70% were teenagers and young adults. Motor Vehicle Accidents (MVAs) contributed to 38% of the injuries followed by falls (28%), sports (19%) and violence (16%); however, etiology differed according to age. Sixty-two percent of the lesions were cervical. Almost 50% were neurologically complete. Sixty-six percent were in wheelchairs. Over 50% were independent in mobility and feeding and nearly 40% were independent in bathing and dressing. Eighty-eight percent returned to their homes. In general, the case at REHAB did not differ from the national database. Because reporting has not been mandatory, actual SCI incidence in Hawaii is most likely higher. Information derived from a mandatory reporting system would lead to identification of high risk groups, development and evaluation of prevention programs, identification of patients requiring early intervention and rehabilitation, and better planning of health care services.

Effect of environmental factors and gender on the heritability of bone mineral density and bone size.

Bone mineral density (BMD), a risk factor for osteoporosis, is believed to be under genetic control. The effect of environmental factors and gender on the heritability of BMD and bone size is ill-defined. In this study, heritability estimates (h2) were determined in 3,320 southern Chinese subjects from 1,019 families using the variance components model. The h2 for age, weight and height-adjusted BMD was 0.63-0.71 for females, and 0.74-0.79 for males; and for bone size, 0.44-0.64 for females and 0.32-0.86 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking and alcohol consumption altered the h2 differently in males and females. The proportion of variance in BMD and bone size explained by all covariates varied between skeletal sites, but was consistently greater in females than males. A significant gender difference was observed in the genetic variance of BMD and bone size at the hip but not the spine. In conclusion, a gender difference was observed in the degree of heritability of BMD and bone size at specific skeletal sites. Environmental influences contributed variably at different sites in the two sexes.