Cognitive restriction accentuates the increased energy intake response to a 10-month multidisciplinary weight loss program in adolescents with obesity.

BACKGROUND: Multidisciplinary interventions have shown some merits in weight reduction strategies in youth, however, their impact on subsequent daily energy intake remains largely unknown. The aim of the present study was to evaluate the nutritional responses to a 10-month multidisciplinary intervention among adolescents with obesity, in relation to their eating behavior characteristics. METHODS: Thirty-five adolescents (mean age: 13.4 ±â€¯1.2 years) with obesity took part in a 10-month residential multidisciplinary weight loss program. Anthropometric measurements, body composition (dual-energy X-ray absorptiometry), 24-h ad libitum energy intake (weighted), eating behaviors (Dutch Eating Behavior Questionnaire) and appetite sensations (Visual Analogue Scales) were assessed on three occasions: at their arrival in the institution (T0), after 5 months (T1), and at the end of the 10-month program (T2). RESULTS: The mean weight loss reached 11% of the adolescents' initial body weight, with an important inter-individual variability (-25% to +3% of their initial body weight). Results revealed sex differences change, with boys showing a higher decrease in fat mass percent and increase in fat-free mass compared with girls. Weight loss was accompanied by a significant decrease in emotional (-8.3%, p < 0.05) and external (-14.8%, p < 0.001) eating scores and a significant increase in 24-h ad libitum energy intake (+246 kcal, p < 0.001). The observed subsequent increased 24-h ad libitum energy intake at T2 compared to T0 was significantly higher in cognitively restrained eaters (+492 kcal) compared to unrestrained eaters (+115 kcal, p = 0,015). Dietary restraint score at baseline was inversely correlated with the percentage of weight loss (r = -0.44, p = 0.010). CONCLUSION: A 10-month multidisciplinary weight loss intervention induced an increase in 24-h ad libitum energy intake compared to baseline, especially in cognitively restrained eaters. Moreover, initially cognitively restrained eaters tended to lose less body weight compared to unrestrained ones. These findings suggest that cognitive restriction may be a useful eating behavior characteristic to consider as a screening tool for identifying adverse responders to weight loss interventions in youth.

Secondary Bone Defect in Neuromuscular Diseases in Childhood: A Longitudinal "Muscle-Bone Unit" Analysis.

To evaluate the potential bone defect in neuromuscular diseases, we conducted a longitudinal study including three groups of patients: 14 Duchenne muscular dystrophies (DMD) and 2 limb-girdle muscular dystrophies (LGMD); 3 Becker muscular dystrophies (BeMD) and 7 spinal muscular atrophies (SMA). Yearly osteodensitometries assessed body composition and bone mineral density (BMD) associated with bone markers and leptin. Along the 7-year study, 107 osteodensitometries showed that bone status evolved to osteopenia in most patients except BeMD. When analyzing the crude values, BMD improved with age in BeMD and SMA but not in DMD/LGMD. The correlation using the Z-scores displayed a decrease in BMD with age in DMD/LGMD for all regions, in SMA at total body less head, whereas BMD increased in BeMD at lumbar spine. As observed in healthy persons, muscular mass and bone tissue were significantly correlated. Glucocorticoids were deleterious on trabecular and cortical bone. Leptin was high in most patients and correlated to fat mass and bone parameters. This study confirms a secondary bone defect in neuromuscular diseases, further confirming the functional relationship between bone and muscle and arguing for regular bone follow-up in patients to prevent fracture risk. Adipose tissue seems to interfere with bone remodeling in neuromuscular diseases.

Gymnastics participation is associated with skeletal benefits in the distal forearm: a 6-month study using peripheral Quantitative Computed Tomography.

OBJECTIVES: Musculoskeletal development of the upper limbs during exposure to weight-bearing loading is under-researched during early pubescent growth. The purpose was to assess the changes in upper body musculoskeletal strength in young girls following 6 months of non-elite gymnastics participation. METHODS: Eighty-four girls, 6-12 years were divided into groups based on gymnastics participation: high-training (HGYM, 6-16 hr/wk), low-training (LGYM, 1-5 hr/wk), and non-gymnasts (NONGYM). Volumetric BMD, bone geometry, estimated bone strength and muscle size were assessed at the non-dominant forearm (4% and 66% radius and ulna) with pQCT. DXA assessed aBMD and body composition. Tests for explosive power, muscle strength, and endurance were also performed. RESULTS: Interaction effects were observed in all variables at the 4% radius. At the 66% ulna, HGYM and LGYM had greater bone mass, size and bone strength than NONGYM, furthermore a dose-response relationship was observed at this location. Body composition was better for HGYM than LGYM and NONGYM, however muscle function was better for HGYM and LGYM than NONGYM. CONCLUSION: The greatest changes were obtained with more than one gymnastics class per week. Separating gymnastics participation-related changes from those associated with normal growth and development remains difficult, particularly at the 4% radius.

Non-elite gymnastics participation is associated with greater bone strength, muscle size, and function in pre- and early pubertal girls.

UNLABELLED: Recent reports indicate an increase in forearm fractures in children. Bone geometric properties are an important determinant of bone strength and therefore fracture risk. Participation in non-elite gymnastics appears to contribute to improving young girls' musculoskeletal health, more specifically in the upper body. INTRODUCTION: The primary aim of this study was to determine the association between non-elite gymnastics participation and upper limb bone mass, geometry, and strength in addition to muscle size and function in young girls. METHODS: Eighty-eight pre- and early pubertal girls (30 high-training gymnasts [HGYM, 6-16 hr/ wk], 29 low-training gymnasts [LGYM, 1-5 h r/wk] and 29 non-gymnasts [NONGYM]), aged 6-11 years were recruited. Upper limb lean mass, BMD and BMC were derived from a whole body DXA scan. Forearm volumetric BMD, bone geometry, estimated strength, and muscle CSA were determined using peripheral QCT. Upper body muscle function was investigated with muscle strength, explosive power, and muscle endurance tasks. RESULTS: HGYM showed greater forearm bone strength compared with NGYM, as well as greater arm lean mass, BMC, and muscle function (+5% to +103%, p < 0.05). LGYM displayed greater arm lean mass, BMC, muscle power, and endurance than NGYM (+4% to +46%, p < 0.05); however, the difference in bone strength did not reach significance. Estimated fracture risk at the distal radius, which accounted for body weight, was lower in both groups of gymnasts. Compared with NONGYM, HGYM tended to show larger skeletal differences than LGYM; yet, the two groups of gymnasts only differed for arm lean mass and muscle CSA. CONCLUSION: Non-elite gymnastics participation was associated with musculoskeletal benefits in upper limb bone geometry, strength and muscle function. Differences between the two gymnastic groups emerged for arm lean mass and muscle CSA, but not for bone strength.

Does exercise modify the effects of zoledronic acid on bone mass, microarchitecture, biomechanics, and turnover in ovariectomized rats?

Regular activity has effects on bone size, shape, and density, resulting in an increase in mechanical strength. The mechanism of action that underlies this improvement in bone strength is mainly linked to an increase in bone formation. Zoledronic acid (Z), in contrast, may prevent bone strength changes in ovariectomized (OVX) rodents by its potent antiresorptive effects. Based on these assumptions we hypothesized that combined effects of exercise (E) and Z may produce higher benefits on bone changes resulting from estrogen deficiency than either intervention alone. At 6 months of age, 60 female Wistar rats were OVX or sham operated (SH) and divided into five groups: SH, OVX, OVX-E, OVX-Z, and OVX-ZE. OVX rats were treated with a single IV injection of Z (20 microg/kg) or vehicle and submitted or not to treadmill exercise (15 m/min, 60 min/day, 5 days/week) for 12 weeks. Whole-body BMD and bone turnover markers were analyzed longitudinally. At sacrifice, femurs were removed. BMD by DXA, three-point bending test, and microCT were performed to study biomechanical and trabecular structure parameters, respectively. After 12 weeks, bone volume fraction decreased in OVX rats, whereas bone turnover rate, trabecular spacing, and structure model index increased compared with those in the SH group (P < 0.05). Zoledronic acid prevented the ovariectomy-induced trabecular bone loss and its subsequent trabecular microarchitectural deterioration. Treadmill exercise running was shown to preserve the bone strength and to induce bone turnover changes in favor of bone formation. However, the combined effects of zoledronic acid and running exercise applied simultaneously did not produce any synergetic or additive effects.

Assessment of trabecular bone microarchitecture by two different x-ray microcomputed tomographs: a comparative study of the rat distal tibia using Skyscan and Scanco devices.

Important aspects of modern skeletal research depend on the phenotypical characterization of trabecular bone microarchitecture as assessed by microcomputed tomography (micro-CT). Until now, however, there have been no studies which compare the two most commonly utilized micro-CT devices, namely, Skyscan and Scanco. The purpose of the current study was to examine the reproducibility and accuracy of these two micro-CT devices in comparison to traditional histomorphometry in ovariectomized rats treated with either propranolol, salbutamol, or vehicle. 6 month old female Wistar rats were ovariectomized (n = 48) or sham operated (n = 12). OVX rats were divided into four groups and then subcutaneously injected with propranolol 0.1 mg/kg/day, propranolol 20 mg/kg/day, salbutamol 3 mg/kg/day, or vehicle for 10 weeks. At sacrifice, the left tibial trabecular bone microarchitecture was analyzed using both the micro-CT Skyscan 1072 (ex vivo) and Scanco vivaCT40 (in vivo). Histomorphometric analysis was performed on the right proximal tibia. Comparisons between the different methods were performed using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots. Correlations were highly significant for all parameters measured between the two micro-CT instruments and were less significant between histomorphometry and micro-CT measurements taken from either the Skyscan or Scanco apparatus. Micro-CT overestimated bone volume compared to histomorphometry. In the ovariectomized rat model, the two micro-CT instruments revealed the same difference between groups whereas histomorphometry revealed only the difference which displayed the largest disparity between groups. In regards to the comparison between the two micro-CT devices, Mountain plot methods indicated that BV/TV, BS/BV, and TbSp were equivalent, whereas a systematic bias was observed for TbN and TbTh. The authors were also able to describe the routine method used to determine the threshold between the two micro-CT devices, which may help explain these differences. While some minor differences in the absolute values of the morphometry parameters exist between the micro-CT measurements from the Skyscan and Scanco instruments, both of these devices display a high degree of accuracy and reproducibility.

Low dose beta-blocker prevents ovariectomy-induced bone loss in rats without affecting heart functions.

Findings from animal studies have suggested that bone remodeling is under beta-adrenergic control. However, the level of adrenergic inhibition required to achieve the most favorable effects on the skeleton remains unknown. To address this question, we compared the effects of low (0.1 mg/Kg/day), medium (5 mg/Kg/day) or high (20 mg/Kg/day) doses of propranolol given 5 days per week for 10 weeks in ovariectomized (OVX) rats. Characteristics of bone microarchitecture, biomechanical properties and bone turnover were investigated, whilst heart functions were assessed by echocardiography and catheterization of the left ventricle. We first confirmed the expression of Adrbeta2R and the absence of Adrbeta1R on osteoblasts by PCR and confocal microscopy. We then showed that low dose propranolol prevented OVX induced bone loss by increasing bone formation (+30% of MAR vs. placebo, P = 0.01) and decreasing bone resorption (-52% of osteoclast surface on bone surface vs. placebo, P = 0.01). Consequently, rats receiving 0.1 mg/kg/day propranolol displayed higher stress (+27%), intrinsic energy (+28.7%) and Young's Modulus in compression versus placebo (all, P < 0.05). No significant effects on heart hemodynamic parameters were found in rats receiving this dose. In contrast, medium and high doses of propranolol had a negative effect on heart functions but no significant protective effects on bone mass in ovariectomized rats. These results, consistent with the dominant nature of the high bone mass phenotype and normal heart function of Adrbeta2R-deficient mice, suggest that low doses of beta-blockers may have a therapeutic utility in the treatment of osteoporosis with high selectivity for bone tissues.

Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture.

INTRODUCTION: Animal studies suggest that bone remodeling is under beta-adrenergic control via the sympathetic nervous system. beta blockers have been suggested to stimulate bone formation and/or inhibit bone resorption in animals as well as to reduce the risk of fracture in humans. The purpose of this study was to examine if these agents can have a preventive or therapeutic effect in osteoporosis. MATERIALS AND METHODS: We have studied the association of beta blockers use with BMD, bone geometry, microarchitecture and fractures rates in postmenopausal women referred for bone density testing. From a total sample of 944 women, we identified 158 women who were taking beta blockers and 341 age-matched women as controls. Bone geometry was investigated at the femoral neck on DXA images. Microarchitecture was evaluated by the H mean fractal parameter at the calcaneus. RESULTS: The odds ratio for fracture (at all sites) in the beta blocker users was 0.56 (95% CI, 0.30-0.99). beta blocker use was associated with a higher BMD at the femoral neck (+4.2%, p<0.05) and L1-L4 (+3.2%, p<0.05). Proximal femur scans revealed significantly higher cortical width (+3.6%, p<0.05) at the femoral neck under beta blockers. Femoral shaft measurement did not significantly differ under beta blockers. Medication use and lifestyle factors indicated no association between beta blockers and smoking, alcohol use, physical activity, corticosteroids and estrogen therapies. The H mean parameter was significantly higher in the beta blockers group (0.619+/-0.029 vs. 0.607+/-0.023 in controls, p<0.05), suggesting a better trabecular microarchitectural organization. CONCLUSION: Our data suggest that the association of current use of beta blockers with low fracture risk is mediated, at least in part, by effects on BMD, cortical bone geometry and trabecular bone microarchitecture.

Doping dose of salbutamol and exercise: deleterious effect on cancellous and cortical bones in adult rats.

Animal studies suggest that bone remodeling is under beta-adrenergic control via the sympathetic nervous system. To our knowledge, the impact of beta-agonist substances, at doping doses, has not been studied in adult rats. The purpose of this study was to examine the effects of salbutamol injections with or without treadmill exercise on trabecular and cortical bone in adult rats. Adult (36 wk of age) female Wistar rats (n = 56) were treated with salbutamol (3 mg.kg(-1).day(-1) sc, 5 days/wk) or vehicle (sham) with or without subsequent treadmill exercise (13 m/min, 60 min/day, 5 days/wk) for 10 wk. Tibial and femoral bone mineral density was analyzed by dual-energy X-ray absorptiometry. Metaphysic trabecular bone structure was analyzed by micro-CT at the time of the animals' death. Bone cell activities were assessed histomorphometrically. After 10 wk, the increase in bone mineral density was less in salbutamol-treated than in sham rats (+3.3% vs. +12.4%, P < 0.05), and trabecular parameters were altered and bone resorption was increased in salbutamol-treated rats compared with controls. The negative effect on bone architecture in salbutamol-treated rats persisted, even with treadmill exercise. These results confirm the deleterious effect of beta(2)-agonists on bone mass during chronic treatment and describe its effects on bone mechanical properties in adult rats. Bone loss occurred independently of a salbutamol-induced anabolic effect on muscle mass and was equally severe in sedentary and exercising rats, despite a beneficial effect of exercise on the extrinsic and intrinsic energy to ultimate strain. These bone effects may have important consequences in athletes who use salbutamol as a doping substance.

Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P < 0.01) and quality (-8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

Preserved bone health in adolescent elite rhythmic gymnasts despite hypoleptinemia.

BACKGROUND/AIMS: Leptin is linked to hormonal disturbances occurring in anorexia and positively linked with bone mineral density. The aim of this study was to determine whether hypoleptinemia occurring in rhythmic gymnasts may affect bone health. METHOD: Leptin, insulin, cortisol, IGF1 levels and bone markers were determined in 36 rhythmic gymnasts (EG) and 20 controls (C). Body composition, BMD at the whole body (WBBMD), lumbar spine (LSBMD) and bone ultrasound properties (SOS, BUA) were measured. RESULTS: The rhythmic gymnasts had lower fat mass and leptin level than the controls. There was no difference for IGF1, cortisol and insulin levels. Bone turnover rate was higher in elite gymnasts. The uncoupling index showed that remodeling favored the bone formation. LSBMD, WBBMD, SOS and BUA were higher in elite gymnasts after adjustment for fat mass. Leptin correlated positively with fat mass and negatively with physical activity. CONCLUSION: High impact training is able to counterbalance bone effects usually encountered in hormonally disturbed subjects. Our results suggest that hypoleptinaemia might be related to direct osteogenic effects and indirect hormonal mechanisms including preservation of IGF and cortisol levels.

Relationships between serum leptin and bone markers during stable weight, weight reduction and weight regain in male and female judoists.

OBJECTIVE: Despite a preliminary understanding of leptin-skeletal interactions, data in humans are inconsistent and the exact roles of leptin on bone metabolism have not yet been defined. The aim of this study was to examine the possible role of leptin in the regulation of bone metabolism in healthy, physically trained adults. METHODS AND DESIGN: Body composition and bone mass (dual-energy X-ray absorptiometry), anthropometry, serum leptin, insulin, cortisol, osteocalcin, C-terminal telopeptide of type I collagen (CTx) and total plasma proteins were measured in judoists at normal body weight, after weight reduction and after weight regain. Physical training, weight cycling history, menstrual status and nutritional intake using a 7-day food record were assessed. RESULTS: Precompetitive weight loss averaged 4 +/- 0.3% of bodyweight and resulted in a significant decrease in leptin levels of 64% (P < 0.001) and of 31% for insulin (P < 0.0001). CTx and cortisol concentrations rose by 33% (P < 0.0001) and 81% (P < 0.05) respectively. Osteocalcin and total plasma protein remained unaffected by weight loss. A 4 +/- 0.5% weight regain induced a 276% increase in leptin levels (P < 0.001) and an 18% increase in insulin (P < 0.001). CTx and cortisol decreased by 23% (P < 0.0001) and 27% (P < 0.05) respectively. Changes in leptin were significantly correlated with changes in bone resorption marker in response to both weight loss (r = 0.56, P < 0.01) and regain (r = 0.44, P < 0.05). CONCLUSIONS: These findings suggest that leptin is involved in the regulation of bone metabolism in healthy adults and might play a potential role in the prevention of osteoporosis.

Bone geometry in response to long-term tennis playing and its relationship with muscle volume: a quantitative magnetic resonance imaging study in tennis players.

The benefit of impact-loading activity for bone strength depends on whether the additional bone mineral content (BMC) accrued at loaded sites is due to an increased bone size, volumetric bone mineral density (vBMD) or both. Using magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA), the aim of this study was to characterize the geometric changes of the dominant radius in response to long-term tennis playing and to assess the influence of muscle forces on bone tissue by investigating the muscle-bone relationship. Twenty tennis players (10 men and 10 women, mean age: 23.1+/-4.7 years, with 14.3+/-3.4 years of playing) were recruited. The total bone volume, cortical volume, sub-cortical volume and muscle volume were measured at both distal radii by MRI. BMC was assessed by DXA and was divided by the total bone volume to derive vBMD. Grip strength was evaluated with a dynamometer. Significant side-to-side differences (P<0.0001) were found in muscle volume (+9.7%), grip strength (+13.3%), BMC (+13.5%), total bone volume (+10.3%) and sub-cortical volume (+20.6%), but not in cortical volume (+2.6%, ns). The asymmetry in total bone volume explained 75% of the variance in BMC asymmetry (P<0.0001). vBMD was slightly higher on the dominant side (+3.3%, P<0.05). Grip strength and muscle volume correlated with all bone variables (except vBMD) on both sides (r=0.48-0.86, P<0.05-0.0001) but the asymmetries in muscle parameters did not correlate with those in bone parameters. After adjustment for muscle volume or grip strength, BMC was still greater on the dominant side. This study showed that the greater BMC induced by long-term tennis playing at the dominant radius was associated to a marked increase in bone size and a slight improvement in volumetric BMD, thereby improving bone strength. In addition to the muscle contractions, other mechanical stimuli seemed to exert a direct effect on bone tissue, contributing to the specific bone response to tennis playing.

Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats.

AIMS: Beta2 adrenergic agonists are widely used in therapeutics and as doping agents by athletes. However, their effects on bone tissue, especially bone microarchitecture, remain poorly understood. Using three-dimensional (3D) microtomography, dual-energy X-ray absorptiometry, biomechanical testing and enzyme-linked immunosorbent assay, we evaluated the effects of two beta2 agonists, clenbuterol and salbutamol, on bone in growing rats. METHODS: Twelve-week-old Wistar female rats (N = 39), divided in 3 groups, received during 6 weeks either salbutamol (4 mg/kg/day), clenbuterol (2 mg/kg/day) or normal saline (0.5 ml/kg/day) by subcutaneous injections. RESULTS: After 6 weeks, the salbutamol and clenbuterol groups displayed lower bone mineral content (BMC), femoral length and cortical width than controls. Clenbuterol treatment further reduced bone mineral density. Bone microarchitecture was clearly altered by clenbuterol, as evidenced by lower trabecular number (-40.40%; P < 0.001), connectivity and trabecular bone volume (-42.85%; P < 0.001), leading to lower ultimate force. Clenbuterol significantly increased muscle mass (P < 0.01) and reduced fat mass when compared to controls. Salbutamol did not seem to have any effect on bone microarchitecture or body composition. Both beta2 agonists increased the bone resorption marker (C-terminal collagen crosslinks) without any change of a bone formation marker. At the end of the treatment, a drop in leptin was seen in the clenbuterol group only. Leptin levels were correlated with BMC (r = 0.69, P = 0.003). CONCLUSION: These results confirm the deleterious effect of beta2 agonists on bone mass and show the negative effects of clenbuterol on trabecular bone microarchitecture. Bone loss occurred independently from muscle mass but was related to fat mass. A leptin-mediated effect on bone tissue seems likely. These pathophysiological effects may have important consequences in human therapeutics and doping.

Cardiorespiratory dynamics to hypoxia at the onset of cycling exercise in male endurance subjects.

AIM: It is well established that altering O2 delivering to contracting skeletal muscle affects human performance. In this respect, a reduced O2 supply (e.g., hypoxia) increases the rate of muscle fatigue. This study aimed to determine the effects of moderate hypoxia and exercise intensity on oxygen uptake (VO2) and cardiac output (CO) kinetics during moderate [below the ventilatory threshold (VT)] and heavy (above VT) constant work rate cycling exercises. METHODS: Eight trained males (age, mean+/-SD, 22+/-3 years; height 182+/-5 cm; body mass 71+/-12 kg) performed at the same relative intensity in normoxic (FIO2=0.21) and hypoxic (FIO2=0.13) conditions moderate and heavy exercises during which pulmonary gas exchange was determined breath-by-breath and CO was monitored beat-by-beat with Doppler echocardiography. RESULTS: The rate of increase (t63%, corresponding to time constant and time delay of a monoexponential response) in CO was significantly faster than that of VO2 in 3 out of 4 experimental conditions (p<0.05). Moreover VO2 kinetics were significantly slowed by hypoxia and speeded by exercise intensity, while CO responses were unaffected by such conditions. A slowed CO response was apparent in hypoxia compared to normoxia (p>0.05) in heavy exercise. CONCLUSIONS: These results suggest an absence of coupling between CO and VO2 kinetics, and that cardiorespiratory O2 delivery is likely different at exercise onset as a function of exercise intensity and FIO2.

Chemical and nonchemical stimuli during breath holding in divers are not independent.

In the breath-hold model described by S. Godfrey and E. J. M. Campbell (Respir. Physiol. 5: 385-400, 1968), chemical and nonchemical stimuli are independent. Because these two factors are time dependent, the effect of each could not be measured by breath-holding time (BHT). The aim of this study is to dissociate chemical and nonchemical stimuli and to assess the effects of BHT and PCO2 on respiratory center output by measurement of occlusion pressure (P0.1) and mean inspiratory flow (VI). Nine well-trained divers (age 36.5 +/- 5.0 yr) took part in the study. Each subject had to hold his breath at 75% of vital capacity for 30, 50, and 70 s of BHT. Before each breath hold, the subject inspired successively two vital capacities of the same CO2-O2 gas mixture. P0.1 and VI were measured during the first reinspiration after the breath hold. For the same BHT, we observed good linear relationships between P0.1 or VI and alveolar PCO2. The slopes of these relationships increased with BHT. For alveolar PCO2 of > 50 Torr, P0.1 increased linearly with BHT. These results indicate that, during breath holding, chemical and nonchemical stimuli acted linearly on respiratory motoneuron activity, but they were not independent.

High-impact loading training induces bone hyperresorption activity in young elite female gymnasts.

The aim of this study was to investigate the effect of intensive exercise on bone turnover (as reflected by bone resorption) in young elite female gymnasts. Forty-five healthy girls including 24 gymnasts (11.9+/-2 yr) and 21 controls (12.3+/-1.4 yr) were studied. Body weight, height, bone age and body composition were measured. Bone mineral density (BMD) was assessed at the whole body, lumbar vertebrae, hip and radius by means of DXA. Volumetric density (BMAD) was calculated. Bone velocity (SOS) and attenuation (BUA) were measured by QUS at the calcaneus. Urinary androstenedione (delta4), dehydroepiandrosterone sulfate (DHEA-S), and CrossLaps (CTx) were measured. BMD and BMAD were significantly greater in the gymnasts at all sites except whole body. SOS was found significantly higher. Delta4 values were significantly lower in the gymnasts. The distribution of the subjects according to Tanner stages was not different between groups. CTx levels were significantly higher in the gymnasts (989.08+/-154.63 microg/mmol Cr.) vs controls (580.25+/-123.99 microg/mmol Cr., p=0.02). CTx values decreased from Tanner stage 1 to stage 4 in each group, the gymnasts' levels always being higher than those of the controls. In conclusion, gymnastics seems to stimulate bone resorption activity in highly-trained young females. The coexistence of bone hyperresorption and higher BMD in gymnasts suggests increased bone turnover resulting in increased bone density in these subjects.

Exercise and zoledronic acid on lipid profile and bone remodeling in ovariectomized rats: a paradoxical negative association?

Exercise (EXE) and amino-bisphosphonates (BP) are both considered as useful strategies in the prevention of post-menopausal bone loss. Exercise reduces lipid levels, and BP may induce increase in high-density lipoprotein cholesterol (HDL-C). We hypothesized that combined effects of BP and exercise would produce a better improvement of lipid profile. We studied the specific and combined effects of zoledronic acid (Z) and EXE on lipid profile and bone remodeling in mature ovariectomized (OVX) rats. Six-month old female rats were randomly assigned to either a sham-ovx group (n = 12) or one of four OVX groups (n = 12): vehicle-treated sedentary (OVX); OVX + EXE (OVX-E, running on a treadmill for 12 weeks); OVX + Z (20 microg/kg, i.v.), (OVX-Z); OVX + Z+EXE (OVX-ZE). Total cholesterol (TC), HDL-C and bone remodeling markers were measured at baseline and at the end of the study. We demonstrated that both Z and EXE prevented the increase in bone resorption resulting from OVX, and individually improved the atherosclerotic risk index. Therapy with Z resulted in significant increase (39.00 +/- 0.03 vs. 53.6 +/- 0.01 mg/dl; +37.4%, P < 0.05) in serum concentration of HDL-C and a non significant decrease in TC (135.30 +/- 0.03 vs. 144.80 +/- 0.05 mg/dl; -5.8%) in the OVX-Z group compared to the OVX group. Post-menopausal women have elevated risk of CVD and bone resorption, hence, these data ultimately demonstrate (except for the elevated ratio in the combined group) that exercise and zoledronic acid are useful in minimizing the impact of these two processes in women and the combination of the two may be clinically relevant.

Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling.

The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg(-1) day(-1) of desipramine, fluoxetine or 10 mg kg(-1) day(-1) of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (-6.1%, p<0.01) and tofisopam higher TbTh (+5.0%, p<0.05) versus placebo. Rolipram and tofisopam treatments induced higher BV/TV than placebo (+23.8% and +18.3% respectively). Desipramine group had significantly higher cortical area (+4.8%, p<0.01) and fluoxetine lower cortical area (-6.1%, p<0.01) compared to placebo. The stiffness and Young's modulus were lower in the fluoxetine group (77+/-13 N mm(-1), 6431+/-1182 MPa) than in placebo (101+/-9 N mm(-1), 8441+/-1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+8.6%) and a lower in fluoxetine (-56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone.