Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

Load carriage exercise increases calcium absorption and retention in healthy young women.

Aerobic exercise reduces circulating ionized Ca (iCa) and increases parathyroid hormone (PTH), but the cause and consequences on Ca handling are unknown. The objective of this study was to determine the effects of strenuous exercise on Ca kinetics using dual stable Ca isotopes. Twenty-one healthy women (26.4 ± 6.7 yr) completed a randomized, crossover study entailing two 6-d iterations consisting of either 60 min of treadmill walking at 65% VO2max wearing a vest weighing 30% body weight on study days 1, 3, and 5 (exercise [EX]), or a rest iteration (rest [REST]). On day 1, participants received intravenous 42Ca and oral 44Ca. Isotope ratios were determined by thermal ionization mass spectrometry. Kinetic modeling determined fractional Ca absorption (FCA), Ca deposition (Vo+), resorption (Vo-) from bone, and balance (Vbal). Circulating PTH and iCa were measured before, during, and after each exercise/rest session. Data were analyzed by paired t-test or linear mixed models using SPSS. iCa decreased and PTH increased (P < .001) during each EX session and were unchanged during REST. On day 1, urinary Ca was lower in the EX pool (25 ± 11 mg) compared to REST (38 ± 16 mg, P = .001), but did not differ over the full 24-h collection (P > .05). FCA was greater during EX (26.6 ± 8.1%) compared to REST (23.9 ± 8.3%, P < .05). Vbal was less negative during EX (-61.3 ± 111 mg) vs REST (-108 ± 23.5 mg, P < .05), but VO+ (574 ± 241 vs 583 ± 260 mg) and VO- (-636 ± 243 vs -692 ± 252 mg) were not different (P > .05). The rapid reduction in circulating iCa may be due to a change in the miscible Ca pool, resulting in increased PTH and changes in intestinal absorption and renal Ca handling that support a more positive Ca balance.

Sex Does Not Affect Changes in Body Composition and Insulin-Like Growth Factor-I During US Army Basic Combat Training.

ABSTRACT: Roberts, BM, Staab, JS, Caldwell, AR, Sczuroski, CE, Staab, JE, Lutz, LJ, Reynoso, M, Geddis, AV, Taylor, KM, Guerriere, KI, Walker, LA, Hughes, JM, and Foulis, SA. Sex does not affect changes in body composition and insulin-like growth factor-I during US army basic combat training. J Strength Cond Res XX(X): 000-000, 2023-Insulin-like growth factor 1 (IGF-I) has been implicated as a biomarker of health and body composition. However, whether changes in body composition are associated with changes in IGF-I is unclear. Therefore, we examined the relationship between body composition changes (i.e., fat mass and lean mass) and total serum IGF-I levels in a large cohort of young men (n = 809) and women (n = 397) attending US Army basic combat training (BCT). We measured body composition using dual energy x-ray absorptiometry and total serum IGF-I levels during week 1 and week 9 of BCT. We found that pre-BCT lean mass (r = 0.0504, p = 0.082) and fat mass (r = 0.0458, p = 0.082) were not associated with pre-BCT IGF-I. Body mass, body mass index, body fat percentage, and fat mass decreased, and lean mass increased during BCT (all p < 0.001). Mean (±SD) IGF-I increased from pre-BCT (176 ± 50 ng·ml-1) to post-BCT (200 ± 50 ng·ml-1, p < 0.001). Inspection of the partial correlations indicated that even when considering the unique contributions of other variables, increases in IGF-I during BCT were associated with both increased lean mass (r = 0.0769, p = 0.023) and increased fat mass (r = 0.1055, p < 0.001) with no sex differences. Taken together, our data suggest that although changes in IGF-I weakly correlated with changes in body composition, IGF-I, in isolation, is not an adequate biomarker for predicting changes in body composition during BCT in US Army trainees.

NSAIDs do not prevent exercise-induced performance deficits or alleviate muscle soreness: A placebo-controlled randomized, double-blinded, cross-over study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently consumed by athletes to manage muscle soreness, expedite recovery, or improve performance. Despite the prevalence of NSAID use, their effects on muscle soreness and performance, particularly when administered prophylactically, remain unclear. This randomized, double-blind, counter-balanced, crossover study examined the effect of consuming a single dose of each of three NSAIDs (celecoxib, 200 mg; ibuprofen, 800 mg; flurbiprofen, 100 mg) or placebo 2 h before on muscle soreness and performance following an acute plyometric training session. Twelve healthy adults, aged 18-42 years, completed a standardized plyometric exercise session consisting of 10 sets of 10 repetitions at 40 % 1-repetition maximum (1RM) on a leg press device. During exercise, total work, rating of perceived exertion, and heart rate were measured. Maximum voluntary contraction force (MVC), vertical jump height, and muscle soreness were measured before exercise and 4-h and 24-h post-exercise. We found no significant differences in total work, heart rate, or rating of perceived exertion between treatments. Additionally, no significant differences in muscle soreness or vertical jump were observed between treatments. Ibuprofen and flurbiprofen did not prevent decrements in MVC, but celecoxib attenuated decreases in MVC 4-h post exercise (p < 0.05). This study suggests that athletes may not benefit from prophylactic ibuprofen or flurbiprofen treatment to prevent discomfort or performance decrements associated with exercise, but celecoxib may mitigate short-term performance decrements.

Changes in Distal Tibial Microarchitecture During Eight Weeks of U.S. Army Basic Combat Training Differ by Sex and Race.

Basic combat training (BCT) is a physically rigorous period at the beginning of a soldier's career that induces bone formation in the tibia. Race and sex are determinants of bone properties in young adults but their influences on changes in bone microarchitecture during BCT are unknown. The purpose of this work was to determine the influence of sex and race on changes in bone microarchitecture during BCT. Bone microarchitecture was assessed at the distal tibia via high-resolution peripheral quantitative computed tomography at the beginning and end of 8 weeks of BCT in a multiracial cohort of trainees (552 female, 1053 male; mean ± standard deviation [SD] age = 20.7 ± 3.7 years) of which 25.4% self-identified as black, 19.5% as race other than black or white (other races combined), and 55.1% as white. We used linear regression models to determine whether changes in bone microarchitecture due to BCT differed by race or sex, after adjusting for age, height, weight, physical activity, and tobacco use. We found that trabecular bone density (Tb.BMD), thickness (Tb.Th), and volume (Tb.BV/TV), as well as cortical BMD (Ct.BMD) and thickness (Ct.Th) increased following BCT in both sexes and across racial groups (+0.32% to +1.87%, all p < 0.01). Compared to males, females had greater increases in Tb.BMD (+1.87% versus +1.40%; p = 0.01) and Tb.Th (+0.87% versus +0.58%; p = 0.02), but smaller increases in Ct.BMD (+0.35% versus +0.61%; p < 0.01). Compared to black trainees, white trainees had greater increases in Tb.Th (+0.82% versus +0.61%; p = 0.03). Other races combined and white trainees had greater increases in Ct.BMD than black trainees (+0.56% and + 0.55% versus +0.32%; both p ≤ 0.01). Changes in distal tibial microarchitecture, consistent with adaptive bone formation, occur in trainees of all races and sexes, with modest differences by sex and race. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Load carriage aerobic exercise stimulates a transient rise in biochemical markers of bone formation and resorption.

Exercise can be both anabolic and catabolic for bone tissue. The temporal response of both bone formation and resorption following an acute bout of exercise is not well described. We assayed biochemical markers of bone and calcium metabolism for up to 3 days after military-relevant exercise. In randomized order, male (n = 18) and female (n = 2) Soldiers (means ± SD; 21.2 ± 4.1 years) performed a 60-min bout of load carriage (30% body mass; 22.4 ± 3.7 kg) treadmill exercise (EXER) or a resting control trial (REST). Blood samples were collected following provision of a standardized breakfast before (PRE), after (POST) exercise/rest, 1 h, 2 h, and 4 h into recovery. Fasted samples were also collected at 0630 on EXER and REST and for the next three mornings after EXER. Parathyroid hormone and phosphorus were elevated (208% and 128% of PRE, respectively, P < 0.05), and ionized calcium reduced (88% of PRE, P < 0.05) after EXER. N-terminal propeptide of type 1 collagen was elevated at POST (111% of PRE, P < 0.05), and the resorption marker, C-terminal propeptide of type 1 collagen was elevated at 1 h (153% of PRE, P < 0.05). Osteocalcin was higher than PRE at 1 through 4 h post EXER (119%-120% of PRE, P < 0.05). Sclerostin and Dickkopf-related protein-1 were elevated only at POST (132% and 121% of PRE, respectively, P < 0.05) during EXER. Trivial changes in biomarkers during successive recovery days were observed. These results suggest that 60 min of load carriage exercise elicits transient increases in bone formation and resorption that return to pre-exercise concentrations within 24 h post-exercise.NEW & NOTEWORTHY In this study, we demonstrated evidence for increases in both bone formation and resorption in the first 4 h after a bout of load carriage exercise. However, these changes largely disappear by 24 h after exercise. Acute formation and resorption of bone following exercise may reflect distinct physiological mechanoadaptive responses. Future work is needed to identify ways to promote acute post-exercise bone formation and minimize post-exercise resorption to optimize bone adaptation to exercise.

Once daily calcium (1000 mg) and vitamin D (1000 IU) supplementation during military training prevents increases in biochemical markers of bone resorption but does not affect tibial microarchitecture in Army recruits.

Basic combat training (BCT) is a period of novel physical training including load carriage resulting in higher risk of stress fracture compared to any other time during military service. Prior trials reported a 20% reduction in stress fracture incidence with Ca and vitamin D (Ca + D) supplementation (2000 mg Ca, 800 IU vitamin D), and greater increases in tibia vBMD during BCT compared to placebo. The primary objective of this randomized, double-blind, placebo-controlled trial was to determine the efficacy of a lower dose of Ca (1000 mg/d Ca, 1000 IU vit D) on PTH, bone biomarkers and tibial microarchitecture during BCT. One hundred volunteers (50 males, 50 females; mean age 21.8 ± 3.5 y) were block randomized by race and sex to receive a daily Ca + D fortified food bar or placebo. Anthropometrics, dietary intake, fasted blood draws and high resolution pQCT scans of the distal and mid-shaft tibia were obtained at the start of BCT and 8 wks later at the conclusion of training. As compliance was 98% in both treatment groups, an intent-to-treat analysis was used. At the distal tibia, total vBMD, Tb.vBMD, Tb.N, Th.Th and Tb.BV/TV increased (+1.07 to 2.12% for all, p < 0.05) and Tb.Sp decreased (0.96 to 1.09%, p < 0.05) in both treatment groups. At the mid-shaft, Ct.Pm increased (+0.18 to 0.21%, p = 0.01) and Ct.vBMD decreased (-0.48 to -0.77%, p < 0.001) in both groups. Ca + D prevented increases in CTX and TRAP, which were observed in the placebo group (group-by-time, p < 0.05). Mean circulating 25OHD, BAP, P1NP and iCa increased and PTH decreased in both treatment groups (p < 0.05). These results, in agreement with other studies, suggest that bone microarchitectural changes indicative of bone formation occur during BCT. While Ca + D supplementation at lower doses than those tested in previous studies prevented increases in biochemical markers of bone resorption in this study, there were no significant changes in bone tissue after 8 wks of Army BCT.

Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk.

There is mounting evidence suggesting that the commonly used analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), may inhibit new bone formation with physical training and increase risk of stress fractures in physically active populations. Stress fractures are thought to occur when bones are subjected to repetitive mechanical loading, which can lead to a cycle of tissue microdamage, repair, and continued mechanical loading until fracture. Adaptive bone formation, particularly on the periosteal surface of long bones, is a concurrent adaptive response of bone to heightened mechanical loading that can improve the fatigue resistance of the skeletal structure, and therefore may play a critical role in offsetting the risk of stress fracture. Reports from animal studies suggest that NSAID administration may suppress this important adaptive response to mechanical loading. These observations have implications for populations such as endurance athletes and military recruits who are at risk of stress fracture and whose use of NSAIDs is widespread. However, results from human trials evaluating exercise and bone adaptation with NSAID consumption have been less conclusive. In this review, we identify knowledge gaps that must be addressed to further support NSAID-related guidelines intended for at-risk populations and individuals.

Growth Hormone and Insulin-like Growth Factor-I Molecular Weight Isoform Responses to Resistance Exercise Are Sex-Dependent.

Purpose: To determine if acute resistance exercise-induced increases in growth hormone (GH) and insulin-like growth factor-I (IGF-I) were differentially responsive for one or more molecular weight (MW) isoforms and if these responses were sex-dependent. Methods: College-aged men (n = 10) and women (n = 10) performed an acute resistance exercise test (ARET; 6 sets, 10 repetition maximum (10-RM) squat, 2-min inter-set rest). Serum aliquots from blood drawn Pre-, Mid-, and Post-ARET (0, +15, and +30-min post) were processed using High Performance Liquid Chromatography (HPLC) fractionation and pooled into 3 MW fractions (Fr.A: >60; Fr.B: 30-60; Fr.C: <30 kDa). Results: We observed a hierarchy of serum protein collected among GH fractions across all time points independent of sex (Fr.C > Fr.A > Fr.B, p ≤ 0.03). Sex × time interactions indicated that women experienced earlier and augmented increases in all serum GH MW isoform fraction pools (p < 0.05); however, men demonstrated delayed and sustained GH elevations (p < 0.01) in all fractions through +30-min of recovery. Similarly, we observed a sex-independent hierarchy among IGF-I MW fraction pools (Fr.A > Fr.B > Fr.C, p ≤ 0.01). Furthermore, we observed increases in IGF-I Fr. A (ternary complexes) in men only (p ≤ 0.05), and increases in Fr.C (free/unbound IGF-I) in women only (p ≤ 0.05) vs. baseline, respectively. Conclusions: These data indicate that the processing of GH and IGF-I isoforms from the somatotrophs and hepatocytes are differential in their response to strenuous resistance exercise and reflect both temporal and sex-related differences.

Randomized Trial Comparing Consumption of Military Rations to Usual Intake for 21 Consecutive Days: Nutrient Adequacy and Indicators of Health Status.

BACKGROUND: The US military Meal, Ready-to-Eat food ration is approved as a nutritionally adequate sole source of nutrition for ≤21 days. However, the ration continuously evolves, requiring periodic reassessment of its influence on nutritional status and health. OBJECTIVE: To determine the effects of consuming the US Armed Services Meal, Ready-to-Eat ration for 21 days, relative to usual diets, on nutrient intake, and indicators of nutritional status and cardiometabolic health. DESIGN: Parallel-arm, randomized, controlled trial, secondary analysis. PARTICIPANTS: Sixty healthy, weight stable, free-living adults from the Natick, MA, area participated between June 2015 and March 2017. INTERVENTION: Participants were randomized to consume their usual diet for 31days (CON), or a strictly controlled Meal, Ready-to-Eat-only diet for 21 days followed by their usual diet for 10 days (MRE). MAIN OUTCOME MEASURES: Nutrient intake (absolute and adjusted) throughout the study period, and indicators of nutrition status (vitamins B, D, folate, homocysteine, iron, magnesium, and zinc) and cardiometabolic health (glucose, insulin, and blood lipid levels) before (Day 0), during (Day 10 through Day 21), and after (Day 31) the intervention period. STATISTICAL ANALYSIS PERFORMED: Between-group differences over time were assessed using marginal models. Models for nutritional status and cardiometabolic health indicators were adjusted for age, initial body mass index, and baseline value of the dependent variable. RESULTS: Energy-adjusted fiber; polyunsaturated fatty acids; vitamins A, thiamin, riboflavin, B-6, C, D, and E; and magnesium and zinc intakes all increased in MRE during the intervention and were higher compared with CON (P<0.05), whereas relative protein intake decreased and was lower (P<0.05). Serum triglyceride concentrations averaged 19% (95% CI 0% to 41%) higher in MRE relative to CON during Days 10 to 31 (P=0.05). No statistically significant effects of diet on any other nutritional status or cardiometabolic health indicators were observed. CONCLUSIONS: Findings demonstrate that a Meal, Ready-to-Eat ration diet can provide a more micronutrient-dense diet than usual dietary intake aiding in maintenance of nutritional status over 21 days.

Biological variation of arginine vasopressin.

PURPOSE: There is growing interest in the measurement of plasma levels of arginine vasopressin (AVP) for the assessment of mild dehydration. However, the principles of biological variation have not been applied to the study of AVP and understanding biological variation of AVP may provide insights regarding measurement thresholds. The purpose of this investigation was to determine the biological variation of AVP in healthy euhydrated individuals to understand the potential for establishing both static and/or change thresholds of importance. METHODS: We studied 29 healthy volunteers (24 men and 5 women) while controlling for hydration and pre-analytical factors. All subjects completed between 2-8 trials where biological variation was determined using widely published methods. We determined the intraindividual, interindividual, and analytical coefficients of variation (CVI, CVG, and CVA, respectively) and subsequently the index of individuality and heterogeneity (II and IH, respectively). RESULTS: AVP did not reach the IH threshold required to be considered useful in the dynamic assessment of physiological deviations from normal. AVP levels approached the II threshold required to be considered useful in the static assessment of physiological deviations from normal. CONCLUSIONS: This analysis demonstrates that AVP assessment is unlikely to yield useful information about hydration status.

Bone turnover is altered during 72 h of sleep restriction: a controlled laboratory study.

PURPOSE: The objective of the study was to evaluate how controlled, short-term sleep restriction (SR; 72 h) alters markers of bone formation and resorption and urinary calcium (Ca) output. METHODS: Ten healthy, sleep-adequate, male soldiers were housed in the research facility one day prior to and for the duration of SR. Diet was controlled to provide adequate energy balance and macronutrient distribution, meeting the recommended dietary allowance (RDA) for Ca. Subjects engaged in light activities to maintain wakefulness and were allowed 2 h of sleep per night (0430-0630 hours). Blood samples were collected each morning at 0 h (baseline) and 24, 48, and 72 h of SR. Serum was assayed for parathyroid hormone (PTH), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type I collagen (CTX). Urine was collected in 24 h increments during SR for measurement of Ca and creatinine (Cr). RESULTS: BAP was reduced at 24 h (P= 0.015) and resorption markers TRAP and CTX were increased after 48 and 72 h of SR compared to baseline (P < 0.05). The ratio of BAP:TRAP was significantly lower (P= 0.017) at 48 and 72 h of SR. In contrast, total 24 h urinary Ca and Ca/Cr excretion were unchanged. CONCLUSIONS: Markers of bone formation and resorption are uncoupled in response to as little as 48 h of SR even when Ca intake is at the RDA. Sleep deprivation may be a risk factor for reduced bone health due to perturbations in bone turnover.

Calcium and vitamin D supplementation and bone health in Marine recruits: Effect of season.

Stress fractures are common overuse injuries caused by repetitive bone loading. These fractures are of particular concern for military recruits and athletes resulting in attrition in up to 60% of recruits that sustain a fracture. Army and Navy recruits supplemented with daily calcium and vitamin D (Ca + D) demonstrated improved bone strength and reduced stress fractures. The aim of the current study was to evaluate whether Ca + D supplementation improves measures of bone health in recruits undergoing United States Marine Corps initial military training (IMT), and whether the effect of supplementation on indices of bone health varied by season. One-hundred ninety-seven Marine recruits (n = 107 males, n = 90 females, mean age = 18.9 ±â€¯1.6 y) were randomized to receive either Ca + D fortified snack bars (2000 mg Ca and 1000 IU vitamin D per day) or placebo divided into twice daily doses during 12 weeks of IMT. Anthropometrics, fasted blood samples, and peripheral quantitative computed tomography (pQCT) scans of the tibial metaphysis and diaphysis were collected upon entrance to- and post-training (12 weeks later). Half of the volunteers entered training in July and the other half started in February. Time-by-group interactions were observed for vitamin D status (25OHD) and the bone turnover markers, BAP, TRAP and OCN. 25OHD increased and BAP, TRAP and OCN all decreased in the Ca + D group (p < .05). Training increased distal tibia volumetric BMD (+1.9 ±â€¯2.8%), BMC (+2.0 ±â€¯3.1%), and bone strength index (BSI; +4.0 ±â€¯4.0%) and diaphyseal BMC (+1.0 ±â€¯2.2%) and polar stress strain index (SSIp; +0.7 ±â€¯2.1%) independent of Ca + D supplementation (p < .05 for all). When analyzed by season, change in BSI was greater in the Ca + D group as compared to placebo in the summer iteration only (T*G; p < .05). No other effects of supplementation on bone tissue were observed. When categorized by tertile of percent change in BSI, recruits demonstrating the greatest changes in BSI and 25OHD entered training with the lowest levels of 25OHD (p < .05). Over all, these results suggest that Ca + D supplementation reduced some markers of bone formation and resorption and the decline in 25OHD over training in volunteers that started training in the summer was prevented by supplementation. Baseline 25OHD and trajectory may impact bone responses to IMT, but little effect of Ca + D supplementation was observed at the investigated doses.

Changes in tibial bone microarchitecture in female recruits in response to 8 weeks of U.S. Army Basic Combat Training.

BACKGROUND: U.S. Army Basic Combat Training (BCT) is a physically-demanding program at the start of military service. Whereas animal studies have shown that increased mechanical loading rapidly alters bone structure, there is limited evidence of changes in bone density and structure in humans exposed to a brief period of unaccustomed physical activity. PURPOSE: We aimed to characterize changes in tibial bone density and microarchitecture and serum-based biochemical markers of bone metabolism in female recruits as a result of 8 weeks of BCT. METHODS: We collected high-resolution peripheral quantitative computed tomographic images of the distal tibial metaphysis and diaphysis (4% and 30% of tibia length from the distal growth plate, respectively) and serum markers of bone metabolism before and after BCT. Linear mixed models were used to estimate the mean difference for each outcome from pre- to post-BCT, while controlling for race/ethnicity, age, and body mass index. RESULTS: 91 female BCT recruits volunteered and completed this observational study (age = 21.5 ±â€¯3.3 yrs). At the distal tibial metaphysis, cortical thickness, trabecular thickness, trabecular number, bone volume/total volume, and total and trabecular volumetric bone density (vBMD) increased significantly by 1-2% (all p < 0.05) over the BCT period, whereas trabecular separation, cortical tissue mineral density (TMD), and cortical vBMD decreased significantly by 0.3-1.0% (all p < 0.05). At the tibial diaphysis, cortical vBMD and cortical TMD decreased significantly (both -0.7%, p < 0.001). Bone strength, estimated by micro finite element analysis, increased by 2.5% and 0.7% at the distal tibial metaphysis and diaphysis, respectively (both p < 0.05). Among the biochemical markers of bone metabolism, sclerostin decreased (-5.7%), whereas bone alkaline phosphatase, C-telopeptide cross-links of type 1 collagen, tartrate-resistance acid phosphatase, and 25(OH)D increased by 10-28% (all p < 0.05). CONCLUSION: BCT leads to improvements in trabecular bone microarchitecture and increases in serum bone formation markers indicative of new bone formation, as well as increases in serum bone resorption markers and decreases in cortical vBMD consistent with intracortical remodeling. Together, these results demonstrate specific changes in trabecular and cortical bone density and microarchitecture following 8 weeks of unaccustomed physical activity in women.

Circulating sclerostin is not suppressed following a single bout of exercise in young men.

The aim of this study was to determine whether an acute bout of exercise reduces serum sclerostin under diet-controlled conditions that stabilize the parathyroid hormone (PTH)-1,alpha-hydroxylase axis. Fourteen male volunteers (age, 22.1 years ± 4.05; BMI, 27.3 kg/m2  ± 3.8) completed a randomized crossover study in which they performed 10 sets of 10 repetitions of plyometric jumps at 40% of their estimated one-repetition maximum leg press or a nonexercise control period. A calcium-controlled diet (1000 mg/day) was implemented prior to, and throughout each study period. Blood was drawn for analysis of serum sclerostin, Dickkopf-1, markers of bone metabolism (PTH, calcium), markers of bone formation (bone alkaline phosphatase, BAP; osteocalcin, OCN), and markers of bone resorption (tartrate-resistant acid phosphatase 5b, TRAP5b; C-telopeptide cross-links of type I collagen, CTX) at baseline and 12, 24, 48, and 72 h following exercise or rest. Changes in serum concentrations were expressed as percentage change from individual baselines. Data were analyzed using a repeated measured linear mixed model to assess effects of time, physical activity status (rest or exercise condition), and the time by activity status interaction. There was a significant effect of exercise on OCN (P = 0.005) and a significant interaction effect for CTX (P = 0.001). There was no effect of exercise on any other biochemical marker of bone metabolism. A single bout of plyometric exercise did not induce demonstrable changes in biochemical markers of bone metabolism under conditions where dietary effects on PTH were controlled.

Sympathetic neurovascular regulation during pregnancy: A longitudinal case series study.

NEW FINDINGS: What is the main observation in this case? The main observation of this case report is that during pregnancy there is a progressive sympatho-excitation in basal conditions and under stress, which is offset by a concurrent reduction in neurovascular transduction. Strong correlations between autonomic nervous system activity and sex hormones (oestrogen and progesterone), vasopressin and aldosterone were found. What insights does it reveal? Our findings suggest that hormonal surges might be associated with central sympathetic activation. ABSTRACT: The adaptations of sympathetic nerve activity (SNA) during pregnancy remain poorly understood. An increase in blood volume, cardiac output and SNA, with a concomitant drop in total peripheral resistance (TPR), suggest that during pregnancy there is a reduced transduction of SNA into TPR. Most of these findings have originated from cross-sectional studies; thus, we conducted a longitudinal assessment of SNA and TPR in two participants. Measurements were made before pregnancy (early follicular phase), on four occasions during pregnancy and at 2 months postpartum. Mean arterial pressure and cardiac output were used to calculate TPR. The SNA was measured using microneurography (peroneal nerve). There was a gestation-dependent increase in SNA burst frequency (r2  = 0.96, P = 0.009). Neurovascular transduction, however, decreased by 53% in both women. Sympathetic hyperactivity was reversed postpartum, whereas neurovascular transduction remained lower. These longitudinal data highlight the progressive sympatho-excitation of pregnancy, which is offset by a concurrent reduction in neurovascular transduction.

Muscle sympathetic nerve activity and volume-regulating factors in healthy pregnant and nonpregnant women.

Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In nonpregnant humans, volume-regulatory factors including plasma osmolality, vasopressin, and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume-regulating factors, including plasma osmolality, plasma renin activity, and arginine vasopressin (AVP). We studied 46 healthy, normotensive young women (23 pregnant and 23 nonpregnant). We measured SNA, arterial pressure, plasma osmolality, plasma renin activity, AVP, and other volume-regulatory factors in resting, semirecumbent posture. Pregnant women had significantly higher resting SNA (38 ± 12 vs. 23 ± 6 bursts/min in nonpregnant women), lower osmolality, and higher plasma renin activity and aldosterone (all P < 0.05). Group mean values for AVP were not different between groups [4.64 ± 2.57 (nonpregnant) vs. 5.17 ± 2.03 (pregnant), P > 0.05]. However, regression analysis detected a significant relationship between individual values for SNA and AVP in pregnant (r = 0.71, P < 0.05) but not nonpregnant women (r = 0.04). No relationships were found for other variables. These data suggest that the link between AVP release and resting SNA becomes stronger in pregnancy, which may contribute importantly to blood pressure regulation in healthy women during pregnancy.NEW & NOTEWORTHY Sympathetic nerve activity and blood volume are both elevated during pregnancy, but blood pressure is usually normal. Here, we identified a relationship between vasopressin and sympathetic nerve activity in pregnant but not nonpregnant women. This may provide mechanistic insights into blood pressure regulation in normal pregnancy and in pregnancy-related hypertension.

Bone formation is suppressed with multi-stressor military training.

PURPOSE: To determine the effects of US Army Ranger Training, an 8-week, physically demanding program (energy expenditure of 2,500-4,500 kcal/day) with energy restriction (deficit of 1,000-4,000 kcal/day) and sleep deprivation (<4 h sleep/night) on bone metabolism. METHODS: Blood was collected from 22 men (age 24 ± 4 years) before and after training. Follow-up measurements were made in a subset of 8 subjects between 2 and 6 weeks after training. Serum was analyzed for bone formation biomarkers [bone alkaline phosphatase (BAP) and osteocalcin (OCN)], bone resorption biomarkers [C-telopeptide cross-links of type I collagen (CTX) and tartrate-resistant acid phosphatase (TRAP5b)], calcium, parathyroid hormone (PTH), and vitamin D 25(OH)D increased significantly by 37.3 ± 45.2 % with training [corrected]. A repeated-measures ANOVA with time as the only factor was used to analyze data on the subset of 8 subjects who completed follow-up data collection. RESULTS: BAP and OCN significantly decreased by 22.8 ± 15.5% (pre 41.9 ± 10.1; post 31.7 ± 7.8 ng/ml) and 21.0 ± 23.3% (pre 15.0 ± 3.5; post 11.3 ± 2.1 ng/ml), respectively, with training, suggesting suppressed bone formation. OCN returned to baseline, while BAP remained suppressed 2-6 weeks post-training. TRAP5b significantly increased by 57.5 ± 51.6% (pre 3.0 ± 0.9; post 4.6 ± 1.4 ng/ml) from pre- to post-training, suggesting increased bone resorption, and returned to baseline 2-6 weeks post-training. PTH Increased significantly by 37.3 ± 45.2% with training. No changes in CTX, calcium, or PTH were detected. CONCLUSIONS: These data indicate that multi-stressor military training results in increased bone resorption and suppressed bone formation, with recovery of bone metabolism 2-6 weeks after completion of training.

Recovery of endocrine and inflammatory mediators following an extended energy deficit.

CONTEXT: Due to current operational requirements, elite soldiers deploy quickly after completing arduous training courses. Therefore, it is imperative that endocrine and inflammatory mediators have fully recovered. OBJECTIVE: Our objective was to determine whether a short-term (2-6 wk) recovery period was sufficient to restore endocrine and inflammatory homeostasis after sustained energy deficit. DESIGN: Before and immediately after the course, serum concentrations of inflammatory and endocrine markers were taken along with anthropometric measures prior to and immediately after the Army Ranger course. In addition, nine soldiers were assessed between 2 and 6 weeks after the course. SETTING: This research occurred in a field setting during an intensive 8-week military training course characterized by high-energy expenditure, energy restriction, and sleep deprivation (U.S. Army Ranger School). PARTICIPANTS: Twenty-three male soldiers (23.0 ± 2.8 y; 177.6 ± 7.9 cm; 81.0 ± 9.6 kg, 16.8 ± 3.9% body fat) participated in this study. INTERVENTIONS: There were no interventions used in this research. OUTCOME MEASURES AND RESULTS: Significant changes occurred in circulating total testosterone (-70%), brain-derived neurotrophic factor (-33%), total IGF-1 (-38.7%), free IGF-1 (-41%), IGF binding protein (IGFBP-6; -23.4%), sex-hormone binding globulin (+46%), thyroid stimulating hormone (+85%), IGFBP-1 (+534.4%), IGFBP-2 (+98.3%), IGFBP-3 (+14.7%), IL-4 (+135%), IL-6 (+217%), and IL-8 (+101%). Significant changes in body mass (-8%), bicep (-14%), forearm (-5%), thigh (-7%), and calf (-2%) circumferences, sum of skinfolds (-52%), and percentage body fat (-54%). All anthropometric, inflammatory, and hormonal values, except T3, were restored to baseline levels within 2-6 weeks after the course. CONCLUSIONS: Endocrine markers and anthropometric measures were degraded, and inflammatory mediators increased after an extended energy deficit. A short-term recovery of 2-6 weeks was sufficient to restore these mediators.

Effects of acute caloric restriction compared to caloric balance on the temporal response of the IGF-I system.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) is a key regulator of metabolism during altered energy states. The IGF-I system components respond to prolonged caloric restriction but it is not clear if this system responds similarly to acute caloric restriction. The purpose of this study was to characterize the IGF-I system response to acute caloric restriction with a secondary purpose of determining if two isocaloric diets with different ratios of carbohydrate to fat alter the IGF-I system under conditions of caloric balance. MATERIALS/METHODS: A double-blind, placebo-controlled crossover design was used in which 27 subjects underwent three, 48-h experimental treatments: 1) caloric restriction 2) carbohydrate and 3) carbohydrate/fat. Blood was sampled periodically (6 time points total) for IGF-I (total and free), IGFBPs1-4, insulin and glucose. ANOVAs were used with significance set at P<0.05. RESULTS: Total IGF-I decreased 7% during CR (P=0.051) and remained stable during CHO and CHO/F. Free IGF-I decreased 43% during CR (P<0.05) and remained stable during CHO and CHO/F. IGFBP-1 increased by 445% during CR (P<0.05) compared to CHO and CHO/F with no changes for IGFBP-2, IGFBP-3 and IGFBP-4. There was no change in glucose or insulin during CR over the course of the study. Insulin and glucose increased (P<0.05) after a meal in both the CHO and CHO/F groups with no difference between these two groups. CONCLUSION: Our findings indicate that free IGF-I decreases and IGFBP-1 increases during caloric restriction, but they are not altered with diets differing in carbohydrate and fat content. Changes in free IGF-I and IGFBP-1 are sensitive to caloric restriction, and their measurement may be valuable in monitoring the physiological response to refeeding in those consuming suboptimal calories.