Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial.

BACKGROUND: Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. METHODS: This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). RESULTS: Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p < 0.0001]) and those taking GLP-1RAs (mean absolute difference 5.2%, p < 0.0001). Proportions of subjects achieving 5% weight loss were significantly greater for NB vs. PL at weeks 26 and 52 among those taking DPP-4is or GLP-1RAs. There were no significant differences in effectiveness observed between NB + DPP-4i and NB + GLP-1RA or between PL + DPP-4i and PL + GLP-1RA in any of the analyses. Serious adverse events were reported by 9.1% and 11.1% for PL + DPP-4i and PL + GLP-1RA, respectively, and 13.3% and 12.4% of NB + DPP-4i and NB + GLP-1RA, respectively. CONCLUSION: NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

Extended-release naltrexone/bupropion and liver health: Pooled, post hoc analysis from four randomized controlled trials.

Sustained weight loss improves liver histology in non-alcoholic fatty liver disease. This post hoc analysis of four phase III, 56-week, randomized controlled trials investigated if extended-release naltrexone and bupropion (NB) affects alanine aminotransferase (ALT) and Fibrosis-4 (FIB-4) index in adults with overweight or obesity. Two thousand and seventy-three subjects (NB = 1310; placebo = 763; 79.0% female; 81.6% Caucasian) had baseline mean weight 101 kg, body mass index 36.2 kg/m2 , ALT 26.9 IU/L and FIB-4 0.79. At 56 weeks, NB-treated subjects experienced more weight loss than placebo (8.7 vs. 3.2 kg, respectively, P < .0001). Weight loss, independent of treatment, was associated with improved ALT and FIB-4 (P < .0001). There was a significant independent effect of NB on change from baseline for FIB-4 (P < .0001), but not for ALT (P = .54). Categorical ALT response (from above to within normal ranges: 10-40 IU/L for men; 7-35 IU/L for women) and achievement of 25% and 50% reduction in ALT were greater for NB versus placebo, and independently affected by weight loss (P < .0001), but not treatment. NB-associated weight loss may improve liver health by normalizing ALT values for those with high baseline levels.

The generalized bone phenotype in children with neurofibromatosis 1: a sibling matched case-control study.

People with neurofibromatosis 1 (NF1) have low bone mineralization, but the natural history and pathogenesis are poorly understood. We performed a sibling-matched case-control study of bone mineral status, morphology, and metabolism. Eighteen children with NF1 without focal bony lesions were compared to unaffected siblings and local population controls. Bone mineral content at the lumbar spine and proximal femur (dual energy X-ray absorptiometry (DXA)) was lower in children with NF1; this difference persisted after adjusting for height and weight. Peripheral quantitative computed tomography (pQCT) of the distal tibia showed that trabecular density was more severely compromised than cortical. Peripheral QCT-derived estimates of bone strength and resistance to bending and stress were poorer among children with NF1 although there was no difference in fracture frequencies. There were no differences in the size or shape of bones after adjusting for height. Differences in markers of bone turnover between cases and controls were in the directions predicted by animal studies, but did not reach statistical significance. Average serum calcium concentration was higher (although within the normal range) in children with NF1; serum 25-OH vitamin D, and PTH levels did not differ significantly between cases and controls. Children with NF1 were less mature (assessed by pubertal stage) than unaffected siblings or population controls. Children with NF1 have a generalized difference of bone metabolism that predominantly affects trabecular bone. Effects of decreased neurofibromin on bone turnover, calcium homeostasis, and pubertal development may contribute to the differences in bone mineral content observed among people with NF1.

Physical activity positively predicts bone architecture and bone strength in adolescent males and females.

AIMS: Physical activity (PA) has positive effects on bone accrual and geometry in children during growth. However, we do not know how PA influences adaptations in bone architecture during growth. We evaluated the contribution of PA to bone density, architecture and strength in adolescents. METHODS: We used HR-pQCT (XtremeCT, Scanco Medical) to assess cross-sectional moments of inertia [Imin, Imax (mm4)], total bone density (Tt.Dn, mg HA/cm³), total bone area (Tt.Ar, mm²), cortical bone density (Ct.Dn, mg HA/cm³), cortical thickness (Ct.Th, µm), trabecular bone density (Tb.Dn, mg HA/cm³), trabecular number (Tb.N, mm⁻¹) and trabecular thickness (Tb.Th, µm) at the distal tibia in 146 male and 132 female participants (15-20 years). We evaluated the contribution of impact loading PA (ImpactPA) and non-impact loading PA (NoimpactPA) on bone (p < 0.05). RESULTS: ImpactPA explained 10% of variance in Imin (p = 0.000), and 12% of variance in Imax (p = 0.000) in male participants. In male participants, ImpactPA explained 6% of variance in Tt.Ar (p = 0.003). In female participants, ImpactPA explained 4% of variance in Tt.Dn (p = 0.011), 5% of variance in Tb.Dn (p = 0.004) and 8% of variance in Tb.N (p = 0.001). CONCLUSION: Our findings suggest that ImpactPA is significantly associated with bone architecture and bone strength in adolescent males and females.

Psychiatric Safety and Weight Loss Efficacy of Naltrexone/bupropion as Add-on to Antidepressant Therapy in Patients with Obesity or Overweight.

There is significant association between obesity and depression. Naltrexone/Bupropion (NB) is indicated for treatment of overweight and obesity (BMI ≥27 kg/m2 with a comorbidity or ≥30 kg/m2). This post-hoc analysis examines safety and efficacy of NB and placebo among individuals with overweight or obesity who were also taking antidepressant therapy during the LIGHT trial (N=8910). Subjects were divided into four subgroups: NB + antidepressants (n=1150), NB without antidepressants (n=3300), placebo + antidepressants (n=1127) and placebo without antidepressants (n=3317). Among subjects taking NB, the combined incidence of serious adverse events (AEs) and AEs leading to treatment discontinuation was not significantly different between those on antidepressants and those who were not. The key weight-loss efficacy analyses were performed on NB or placebo-treated subjects who remained on study therapy through 104 weeks and who did or did not have documented antidepressant use at each of the baseline, week 52 and week 104 visits (Completers: N=1811; 47.0% female, 86.9% white, mean age of 61 years, mean baseline BMI 37.4 kg/m2). The mean adjusted weight change in subjects taking antidepressants was numerically, but not significantly greater for NB vs. placebo (-6.3% vs. -4.3%). For those subjects not on antidepressants, weight loss was significantly greater for NB vs. PL (-6.8% vs. -3.6%). NB is generally well tolerated in patients with overweight or obesity who are on antidepressants and is effective in promoting weight loss regardless of antidepressant use. These results show that for patients on antidepressant therapy, NB may be an effective option for obesity management.

Site specificity of bone architecture between the distal radius and distal tibia in children and adolescents: An HR-pQCT study.

High-resolution quantitative computerized tomography permits evaluation of site specific differences in bone architecture. The purpose of this study was to compare bone architecture between distal radius and distal tibia. We present bone architecture at the distal radius and distal tibia in 151 male and 172 female participants, as follows: total bone area (mm(2)), total bone density (mg HA/cm(3)), trabecular bone density (mg HA/cm(3)), cortical bone density (mg HA/cm(3)), cortical thickness (µm), trabecular number (1/mm), trabecular thickness (µm), and trabecular separation (µm). We evaluated differences in and correlations between bone variables (absolute values) across sites. We calculated individual z scores and used regression to assess discordance between sites. In pubertal and postpubertal male and female participants, absolute values of total bone area, cortical bone density, cortical thickness, and trabecular thickness were significantly lower at the radius compared with the tibia (P < 0.01). Absolute values for trabecular bone density were significantly lower at the radius compared with the tibia in postpubertal male and female participants (P < 0.01). Absolute values for trabecular separation was significantly lower at the radius compared with the tibia in pubertal female participants (P < 0.01). Bone architecture was moderately to highly correlated between sites (r = 0.34-0.85). There was discordance between z scores at the radius and tibia within male participants (pubertal R (2) between 36 and 64%; postpubertal R (2) between 22 and 77%) and female participants (pubertal R (2) between 10 and 44%; postpubertal R (2) between 25 and 62%). In conclusion, it is vital to evaluate bone architecture at the specific skeletal site of interest.

Assessing bone microstructure at the distal radius in children and adolescents using HR-pQCT: a methodological pilot study.

We examined the use of high-resolution peripheral quantitative computed tomography (HR-pQCT [XtremeCT; Scanco Medical, Switzerland]) to assess bone microstructure at the distal radius in growing children and adolescents. We examined forearm radiographs from 37 children (age 8-14 yr) to locate the position of the ulnar and radial growth plates. We used HR-pQCT to assess bone microstructure in a region of interest (ROI) at the distal radius that excluded the growth plate (as determined from the radiographs) in all children (n=328; 9-21 yr old). From radiographs, we determined that a ROI in the distal radius at 7% of bone length excluded the radial growth plate in 100% of participants. We present bone microstructure data at the distal radius in children and adolescents. From the HR-pQCT scans, we observed active growth plates in 80 males (aged 9.5-20.7 yr) and 92 females (aged 9.5-20.2 yr). The ulnar plate was visible in 9 male and 17 female participants (aged 11.2 ± 1.9yr). The HR-pQCT scan required 3 min with a relatively low radiation dose (<3 µSv). Images from the radial ROI were free of artifacts and outlined cortical and trabecular bone microstructure. There is currently no standard method for these measures; therefore, these findings provide insight for investigators using HR-pQCT for studies of growing children.

Regional variability in Canadian routine care of type 2 diabetes, hypercholesterolemia, and hypertension: Results from the The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry.

BACKGROUND: Regional differences in the profile and treatment strategies of patients with cardiometabolic diseases have been studied in several different countries. The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry was designed to evaluate patient profiles and medical management of cardiometabolic diseases in routine clinical care settings across Canada. Primary objectives were to (1) evaluate regional variability of patient profiles with cardiometabolic disease(s) and (2) assess treatment differences of patients treated for type 2 diabetes (T2D), hypercholesterolemia (HCh), and hypertension (HTN) across Canada. METHODS: CV-CARE is a multi-center, observational, prospective registry that enrolled Canadian patients treated with metformin-extended release (MetER) for T2D, colesevelam (C) for HCh, azilsartan (AZI) for mild-to-moderate essential HTN and azilsartan/chlorthalidone (AZI/CHL) for severe, essential HTN. Patient characteristics and treatments were assessed at baseline. RESULTS: The registry enrolled 6960 patients, with a total of 4194 patients making up the primary analysis population [MetER (n=995); C (n=1639); AZI (n=1364); AZI/CHL (n=498)]. First-line use of MetER was more common in British Columbia (BC; 45.5%) compared to Ontario (ON; 29.8%), and Quebec (QC; 12.9%). C treatment for HCh was used as monotherapy most readily in BC (68.7%) compared with QC (59.7%) and ON (35.8%). Dual action of low-density lipoprotein cholesterol and hemoglobin A1c reduction was the predominant reason for C add-on therapy (46.8%), with highest usage seen in ON (62.9%). AZI treatment for HTN was most frequently used in BC (43.8%), and AZI/CHL was most commonly used in ON (12.0%). First-line use of AZI was more common in QC (50%) vs. ON (34.9%) and BC (24.1%). The primary reason for switching to AZI and AZI/CHL from prior treatment was lack of efficacy across provinces. CONCLUSION: This is the first regional description of the CV-CARE cohort. Significant variations in both baseline profile and treatments were observed which could have an impact on long-term outcomes.

Real-world effectiveness of treatments for type 2 diabetes, hypercholesterolemia, and hypertension in Canadian routine care - Results from the CardioVascular and metabolic treatment in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry, 12-months results.

AIMS: The CV-CARE registry provides RWE in Canadian routine clinical practice. METHODS: CV-CARE is a multi-site, observational, prospective Canadian registry enrolling patients initiating treatment with metformin hydrochloride extended-release (MetER) for T2D; colesevelam (C) for HCh; and azilsartan (AZI), azilsartan/chlorthalidone (AZI/CHL) or diltiazem extended-release (TXC) for HTN. Patient characteristics/assessment were performed at baseline and 12 ± 6 months. Primary outcome was absolute change in HbA1c and FPG (MetER); % change in LDL-C (C); and absolute change in BP (AZI-AZI/CHL-TXC). RESULTS: Of the 4194 patients in the primary analysis population, 24% were taking MetER, 39% were taking C, 33% were taking AZI, 12% were taking AZI/CHL, and 3% were taking TXC. At 12 months, MetER-treated patients had an absolute mean (95% CI) change in HbA1c of -0.3% [-0.4; -0.2] and in FPG of 0.7 mmol/L [-1.0; -0.4]. C-treated patients had a mean (95% CI) % change in LDL-C of -13.0% [-14.6; -11.4]. Absolute mean (95% CI) changes in SBP were -18.7 mmHg [-19.7; -17.7](AZI), -21.3 mmHg [-23.1; -19.5](AZI/CHL), and -12.3 mmHg [-15.1; -9.6](TXC). CONCLUSION: In a real-world Canadian setting, MetER, C, AZI, AZI/CHL, and TXC show improvement of the cardiometabolic profile of T2D, HCh, and HTN patients.

Bone mineral accrual across growth in a mixed-ethnic group of children: are Asian children disadvantaged from an early age?

We investigated the contribution of ethnicity, physical activity, body composition, and calcium intake to bone accrual across 7 years of growth. We assessed 80 Caucasian and 74 Asian boys and 81 Caucasian and 64 Asian girls at baseline and retained 155 children across all 7 years. Ethnicity, physical activity, and calcium intake were assessed by questionnaire; fat mass, lean mass, and bone mineral content (BMC) of the whole body (WB), lumbar spine (LS), total proximal femur (PF(TOT)), and femoral neck (FN) were measured using DXA (Hologic QDR 4500). We aligned children on peak height velocity and utilized multilevel modeling to assess bone mineral accrual. Height and lean mass accounted for 51.8% and 44.1% of BMC accrual in children. There was a significant difference in physical activity, calcium intake, and lean mass between Asians and Caucasian boys and girls at baseline and conclusion (p < 0.05). In boys, physical activity and ethnicity significantly predicted BMC accrual at the FN. In girls, Asians had significantly lower PF(TOT) and FN BMC. Calcium was a significant predictor of WB BMC accrual in boys and girls. In conclusion, our findings highlight the importance of accounting for ethnicity in pediatric studies. Physical activity, dietary calcium, and lean mass positively influence bone accrual and are lower in Asian compared to Caucasian children from a very young age.

Bone and muscle parameters of the tibia: agreement between the XCT 2000 and XCT 3000 instruments.

Peripheral quantitative computed tomography is a valuable tool to assess bone in children across growth, with long-term studies capturing nuances missed in cross-sectional studies. As children grow, a change from XCT 2000 to a XCT 3000 may be required to accommodate the increasing size of the lower limbs. We examined the precision and agreement between the Stratec XCT 2000 and 3000 on selected bone and muscle parameters. Twenty-eight participants (mean+/-SD; age 27.5+/-6.5 yr) underwent scans at the distal (8%), mid (50%), and proximal (66%) tibia sites, to assess total bone area, total bone density, and trabecular density (8% site); and total bone area, cortical area, cortical density (CoD), polar strength-strain index, and muscle cross-sectional area (50% and 66% sites). Outcomes between instruments were highly correlated; r=0.90-0.99 for CoD across sites, with r=0.97-0.99 for all other measures. Bland and Altman plots showed excellent agreement between instruments for all variables. Regression indicated no significant relationship between instrument and size of measurement (p>0.05). Coefficients of variation were lower than previously reported (0.4-2.4%). For longitudinal studies, the XCT 3000 can replace the XCT 2000 with minimal influence on bone and muscle parameters.

The influence of oral contraceptives on athletic performance in female athletes.

It is now estimated that the prevalence of oral contraceptive use in athletic women matches that of women in the general population. The oral contraceptive pill (OCP) reduces cycle-length variability and provides a consistent 28-day cycle by controlling concentrations of endogenous sex hormones. The OCP is administered in three different forms that differ widely in chemical constitution and concomitant effects on the human body. As fluctuation in sex steroids are believed to be a possible causal factor in performance and exercise capacity, it is imperative to understand the effect of administering the various types of OCP on women. However, the research into oral contraceptives and exercise performance is not consistent. The type of OCP administered (monophasic, biphasic or triphasic), as well as the type and dose of estrogen and progestogen within, will have varying effects on exercise. To date, research in the area of oral contraceptives and exercise capacity is sparse and much has been plagued by poor research design, methodology and small sample size. It is clear from the research to date that more randomised clinical trials are urgently required to assess the array of OCP formulations currently available to women and their concomitant effect on health and exercise capacity. Therefore, the purpose of this article is to critically appraise the literature to date and to provide a current review of the physiological scientific knowledge base in relation to the OCP and exercise performance. In addition, methodological control, design and conduct will be considered with future areas of research highlighted.

Exercise and bone mineral accrual in children and adolescents.

Osteoporosis is a serious skeletal disease causing an increase in morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. Indeed, there has been a large emphasis on the prevention of osteoporosis through the optimization of peak bone mass during childhood and adolescence. The prepubertal human skeleton is sensitive to the mechanical stimulation elicited by exercise and there is increasing evidence that regular weight-bearing exercise is an effective strategy for enhancing bone mineral throughout growth. Physical activity or participation in sports needs to start at prepubertal ages and be maintained through pubertal development to obtain the maximal peak bone mass achievable. High strain eliciting sports like gymnastics, or participation in sports or weight bearing physical activity like soccer, are strongly recommended to increase peak bone mass. Many other factors also influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet and endocrine status. However, this review article will focus solely on the effects of physical activity and exercise providing a summary of current knowledge on the interplay between activity, exercise and bone mass development during growth. Due to the selection bias and other confounding factors inherent in cross-sectional studies, longitudinal and intervention studies only will be reviewed for they provide a greater opportunity to examine the influence of mechanical loading on bone mineral accretion over time. Key pointsPre-pubertal children's ability to thermoregulate when exposed to hot and humid environments is deficient compared to adults.Research into the severity of heat-related illness in pre-pubertal children is inconclusive.Discretion should be used in applying findings from indoor studies to outdoor activities due to the influence of the velocity of circulating air on thermoregulation.

Androgenicity of the progestin in oral contraceptives does not affect maximal leg strength.

PURPOSE: This study was conducted to examine androgenicity of the progestin in oral contraceptive pills and its effect on maximal leg strength in females. METHODS: Twelve participants who were using a monophasic pill containing 30 microg ethinylestradiol plus either 150 microg levonorgestrel (LEV) or 250 microg norgestimate (NOR) for at least the last 6 months were recruited (mean+/-SEM; LEV: age, 19.8+/-0.3 years; stature, 1.67+/-0.17 m; mass, 65.9+/-1.9 kg; NOR: age, 20.6+/-0.2 years; stature, 1.65+/-0.17 m; mass, 64.6+/-2.4 kg). Three maximal isokinetic extension and flexion tests were performed on three occasions (Days 3-6, 11-14 and 18-21 of the pill cycle) to assess peak extension and peak flexion torque (in Newton meters). RESULTS: No significant (p>.05) differences were found in the LEV and NOR groups in peak extension torque (F=0.719; p=.416) or peak flexion torque (F=0.291, p=.601) throughout the pill cycle and between groups. CONCLUSION: In this small study, the androgenicity of the progestin in the contraceptive pill had no significant association with maximal strength in these female athletes.

Does lower-body BMD develop at the expense of upper-body BMD in female runners?

PURPOSE: Evidence suggests that exercise plays an important role in stimulating site-specific bone mineral density (BMD). However, what is less well understood is how these benefits dissipate throughout the body. Hence, the purpose of the present study was to compare the levels of, and the correlation between, BMD recorded at 10 sites in female endurance runners, and to investigate possible determinants responsible for any inter-site differences observed. METHODS: Repeated measures ANOVA was used to compare the BMD between sites and factor analysis was used to describe the pattern of intersite correlations. Allometric ANCOVA was used to identify the primary determinants of bone mass and how these varied between sites. RESULTS: The ANOVA and factor analysis identified systematic differences in BMD between sites, with the greatest BMD being observed in the lower-body sites, in particular the legs. An investigation into the possible mechanisms responsible for these differences revealed "distances run" (km.wk-1) as a positive, and "years of training" as a negative determinant of bone mass (P < 0.001). However, the effect of a number of determinants varied between sites (P < 0.05). Specifically, the ANCOVA identified that running further distances resulted in higher bone mass in the arms and legs. In contrast, training for additional years appeared to result in lower bone mass in the arms and lumbar spine. Calcium intake was also found to be positively associated with bone mass in the legs but negatively associated at all other sites. CONCLUSIONS: A combination of running exercise and calcium intake would appear to stimulate the bone mass of women endurance runners at lower-body sites but at the expense of bone mass at upper-body sites.

Bone microstructure at the distal tibia provides a strength advantage to males in late puberty: an HR-pQCT study.

Bone is a complex structure with many levels of organization. Advanced imaging tools such as high-resolution (HR) peripheral quantitative computed tomography (pQCT) provide the opportunity to investigate how components of bone microstructure differ between the sexes and across developmental periods. The aim of this study was to quantify the age- and sex-related differences in bone microstructure and bone strength in adolescent males and females. We used HR-pQCT (XtremeCT, Scanco Medical, Geneva, Switzerland) to assess total bone area (ToA), total bone density (ToD), trabecular bone density (TrD), cortical bone density (CoD), cortical thickness (Cort.Th), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular spacing standard deviation (Tb.Sp SD), and bone strength index (BSI, mg2/mm4) at the distal tibia in 133 females and 146 males (15 to 20 years of age). We used a general linear model to determine differences by age- and sex-group and age x sex interactions (p<0.05). Across age categories, ToD, CoD, Cort.Th, and BSI were significantly lower at 15 and 16 years compared with 17 to 18 and 19 to 20 years in males and females. There were no differences in ToA, TrD, and BV/TV across age for either sex. Between sexes, males had significantly greater ToA, TrD, Cort.Th, BV/TV, Tb.N, and BSI compared with females; CoD and Tb.Sp SD were significantly greater for females in every age category. Males' larger and denser bones confer a bone-strength advantage from a young age compared with females. These structural differences could represent bones that are less able to withstand loads in compression in females.

International longitudinal pediatric reference standards for bone mineral content.

To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site-specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Women's Health Study (n=112) and Stanford's Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement between predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P<0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. We report similar findings for the PF and FN. Models for females for all sites were similar with age, height and weight as independent significant predictors of BMC accrual (P<0.05). We provide a tool to calculate a child's BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in pediatrics we recommend standards that are sex, age, size and ethnic specific.

The components of the female athlete triad do not identify all physically active females at risk.

The purpose of the present study was to assess the effectiveness of the triad components (amenorrhoea, disordered eating, and osteoporosis) in identifying physically active women at risk of long-term health problems. Eighty-two females (mean age 31.1 years, s = 6.7; body mass 58.4 kg, s = 6.6; stature 1.65 m, s = 0.06) completed training, menstrual, and dietary questionnaires. Bone mineral density and size-adjusted bone mineral density were assessed at the femoral neck and lumbar spine using dual energy X-ray absorptiometry. Seventy-eight percent of participants were eumenorrhoeic, 20% were oligomenorrhoeic, and 2% were amenorrhoeic. Thirty-six percent and 55% reported disordered eating practices in the present and past respectively. Eighty-one percent, 17%, and 2% were classified as normal, osteopaenic, and osteoporotic at the femoral neck respectively; 92% were normal, 7% osteopaenic, and 1% osteoporotic at the lumbar spine. No significant differences in femoral neck size-adjusted bone mineral density were observed between eumenorrhoeic and oligo/amenorrhoeic participants (F(2,80) = 0.119, P = 0.73); eumenorrhoeic participants had significantly greater lumbar spine size-adjusted bone mineral density (F(2,80) = 9.79, P = 0.003). Disordered eating participants had significantly lower femoral neck size-adjusted bone mineral density than those reporting no disordered eating (F(2,80) = 13.816, P = 0.000). Twenty-two percent of participants fulfilled triad criteria, while 55% were "at risk" of long-term health problems. An accumulation of conditions resulted in lower lumbar spine size-adjusted bone mineral density (F(1,80) = 6.074, P = 0.004). The current triad components do not identify all women "at risk" and more appropriate criteria such as exercise-related menstrual alterations, disordered eating, and osteopaenia are suggested.