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.

Cardiac resynchronization therapy (CRT) results in improved clinical status in patients with heart failure and left ventricular dyssynchrony. One third of CRT patients fail to respond due to the inability to 1) identify non-responders prior to treatment, 2) optimize coronary sinus lead placement for left ventricular pacing and 3) optimize the atrio-ventricular (A-V) and inter-ventricular (V-V) intervals. Although invasive measurements of first maximal derivative of left ventricular pressure (dP/dt(max)) are used to optimize lead placement and A-V and V-V intervals in CRT, it would be preferable to have a non-invasive assessment of dP/dt(max). Echocardiographic dyssynchrony and left ventricular function are current parameters for non-invasively evaluating responders to CRT, but they are not recommended due to their poor reproducibility. We applied recent advances in technology to develop a device called the digital ballistocardiograph (dBG (R)), which assesses the mechanical function of the heart using triaxial accelerometry. We show that dBG (R) cardiac events are valid in comparison to 2D transthoracic echocardiography and reliable in comparison to cardiac magnetic resonance imaging. We present preliminary data to support our position that the dBG (R) could be used as a non-invasive assessment of dP/dt(max) in heart failure patients to identify responders and optimize CRT.

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.

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 (mm 4 )], total bone density (Tt.Dn, mg HA/cm 3 ), total bone area (Tt.Ar, mm 2 ), cortical bone density (Ct.Dn, mg HA/cm 3 ), cortical thickness (Ct.Th, μm), trabecular bone density (Tb.Dn, mg HA/cm 3 ), 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.

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.

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.

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.

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 (mm2), total bone density (mg HA/cm3), trabecular bone density (mg HA/cm3), cortical bone density (mg HA/cm3), 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.

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.

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.

Recent results suggest that ultrastructural bone phenotypes, such as the cortical canal network and the osteocyte lacunar system, could be directly linked to the mechanical failure behavior of bone tissue. Moreover, we recently established a synchrotron radiation (SR)-based computed tomography (CT) method, allowing volumetric quantitative morphometry of bone ultrastructure and microdamage (Figure), where microdamage is believed to be a precursor of mechanical failure. Consequently, the aim of this study was to investigate quantitatively the eect of the canal network on microcrack initiation, propagation, and accumulation in two inbred strains of mice, C57BL/6 (B6) and C3H/He (C3H). We hypothesize that dierences in the canal network will help to better predict microdamage in cortical bone. Seven femora each from 16-week-old female B6 and C3H mice were embedded at both ends into polymethyl methacrylate (PMMA) cement. Additionally, a round notch was created in the proximal quadrant of the mid-diaphysis, where microcracks initiated and propagated while the bone was loaded using image-guided failure assessment (IGFA). During compression at 1% apparent strain, a high-resolution 3D image (700 nm nominal resolution) was acquired using SR CT. For morphometry, the canal network (Ca) and microcracks (Cr) were extracted as two separate phases. For each phase, a set of morphometrical indices were measured, such as canal volume density (Ca.V/Ct.V), canal unit volume (Ca.V/N.Ca), and crack number density (N.Cr/Ct.V) , where Ct.V, N.Ca and N.Cr refer to cortical bone volume, number of canals and number of cracks, respectively. Relationships between Ca and Cr indices were computed by linear regression analysis. Results from linear regression analysis involving both mouse strains showed that cannular indices were strongly associated to microcrack behavior. Canal volume density (R = 0.64, p , 0.005) and canal unit volume (R = 0.75, p , 0.001) both predicted the number of microcracks per unit volume of cortical bone. Classical morphometric indices correlated only moderately with the number of microcracks (data not shown here), where cortical thickness (R = 0.45) showed the highest correlation among them. In conclusion, we showed for the first time how bone ultrastructure predicts number of microcracks and consequently how bone ultrastructure contributes to bone strength. These new findings shed new light on the complex relation between bone quality and bone competence and might help to better understand human bone diseases like osteoporosis. Figure: Canal network (tubes in red), osteocyte lacunae (prolate ellipsoids in yellow) and microcrack (green cleft) within murine cortical bone (semitransparent shell in blue) of the femoral mid-diaphysis. Disclosures: Philipp Schneider, None.

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 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.

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 mu g ethinylestradiol plus either 150 mu g levonorgestrel (LEV) (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; or 250 go norgestimate 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. (c) 2006 Elsevier Inc. All rights reserved.

Velocity at VO2 max (vV̇O2 max) and peak treadmill velocity (PTV) are variables highly predictive of endurance performance. However, how these variables are affected by the menstrual cycle is unknown. The aim of this study was to assess the effect of the menstrual cycle on vV̇O2 max and PTV. Ten, female runners were studied across three menstrual cycles. Training, menstrual history and mood states were assessed for 2 months, with daily salivary samples taken to detect menstrual phases. During the third menstrual cycle, participants completed a maximal test to determine V̇O2 max, vV̇O2 max and PTV in the early follicular phase, late follicular phase, early luteal phase, late luteal phase and menses. Progesterone increased at the onset of the luteal phase [mean (SEM); 490 (73.6) pmol l−1] compared to the follicular phase [344.6 (59.7) pmol l−1). No significant differences in the psychological mood states between the phases of the menstrual cycle were found (P>0.05). No significant differences in vV̇O2 max (P=0.611), or PTV (P=0.472) were found between the phases of the menstrual cycle. Thus, vV̇O2 max and PTV are not affected by the monthly menstrual cycle in female endurance 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.

This study investigated heart-rate (HR) and lactate responses of 31 club-level orienteers (age 23-68 years) during competitions in technically easy (TE) and technically difficult (TD) terrain. HR was monitored throughout the events, and capillary-blood samples for lactate analysis were taken at a midpoint and at the finish. HR and lactate responses were relatively consistent within and between events. Orienteering speed and mean lactate levels were lower in the more complex terrain (TE 5.6 vs. TD 4.1 mmol/L). Age was not a predictor of lactate values. The peak HR for both events was 175 ± 10 beats/min and decreased with age by 2–5 beats · min · decade−1. Mean HR was TE, 162 ± 11, and TD, 156 ± 14 beats/min, and did not decline with age. Participants older than 45 years frequently displayed peak and mean HR responses exceeding those predicted from commonly applied age-related algorithms.

PURPOSE The aim of this study was to assess the validity and reliability of the Biosen 5030 lactate analyzer compared with a YSI 2300 lactate analyzer and a Kodak Ektachem DTII in a practical laboratory study context. METHODS To assess validity, 144 triplicate capillarized blood samples, across a range of values, were analyzed using the three analyzers. To assess reliability a further 665 samples were repeat analyzed. Temporal stability was determined by the reanalysis of resting and maximal exercise blood samples, after a period of storage ranging from 7 to 20 h, at room temperature. To measure inter- and intra-investigator reliability, 20 resting samples were taken from three different subjects by different investigators and a coefficient of variation was determined. RESULTS There were strong relationships between the Biosen, the YSI (r2 = 0.97), and the Kodak Ektachem (r2 = 0.91). An analysis of Biosen compared with YSI revealed a positive bias of 0.37 mmol x L(-1) (95% limits of agreement, -0.85 to 1.59 mmol x L(-1)). The test-retest reliability correlation was significant (r2 = 0.99, P < 0.05), but a paired t-test revealed a small (0.03 mmol x L(-1), P < 0.05) significant difference. The coefficient of variation from the three investigators across the 20 samples ranged from 1.3 to 3%. Blood lactate concentration in resting blood samples did significantly increase in value (0.2 mmol x L(-1), P < 0.05) after 7-h exposure to the air, whereas there was no change in maximal exercise blood lactate values after 20-h exposure to the air. CONCLUSIONS In a practical context, the Biosen 5030 lactate analyzer was comparable to the other analyzers giving fast reliable measures of blood lactate concentrations over the full range of values, which remained stable over extended periods at room temperature.