Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10−8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150; n = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75; n = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200; n = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (−1.91 ± 0.99 kilograms) almost entirely due to fat loss (−1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (−1.60 ± 1.06 kilograms; P = 0.46 versus 75:75) but with attenuated reductions in body fat (−0.74 ± 1.32 kilograms; P = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (−0.52 ± 1.09 kilograms; P ≤ 0.04 versus 75:75 and 0:150) or fat mass (−0.12 ± 0.68 kilograms; P ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups (P > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health.

Bone (re)modelling markers can help determine how bone responds to different types, intensities and durations of exercise. They might also help predict those at risk of bone injury. We synthesised evidence on the acute and chronic bone metabolic responses to exercise, along with how nutritional factors can moderate this response. Recommendations to optimise future research efforts are made. IN BRIEF:Bone (re)modelling markers elucidate the dynamic bone response to exercise and if used appropriately have large potential to progress understanding.

Bone resorption is increased after running, with no change in bone formation. Feeding during exercise might attenuate this increase, preventing associated problems for bone. This study investigated the immediate and short-term bone metabolic responses to carbohydrate (CHO) feeding during treadmill running. Ten men completed two 7-day trials, once being fed CHO (8% glucose immediately before, every 20 min during, and immediately after exercise at a rate of 0.7 g CHO·kg body mass−1·h−1) and once being fed placebo (PBO). On day 4 of each trial, participants completed a 120-min treadmill run at 70% of maximal oxygen consumption (V̇o2 max). Blood was taken at baseline (BASE), immediately after exercise (EE), after 60 (R1) and 120 (R2) min of recovery, and on three follow-up days (FU1-FU3). Markers of bone resorption [COOH-terminal telopeptide region of collagen type 1 (β-CTX)] and formation [NH2-terminal propeptides of procollagen type 1 (P1NP)] were measured, along with osteocalcin (OC), parathyroid hormone (PTH), albumin-adjusted calcium (ACa), phosphate, glucagon-like peptide-2 (GLP-2), interleukin-6 (IL-6), insulin, cortisol, leptin, and osteoprotogerin (OPG). Area under the curve was calculated in terms of the immediate (BASE, EE, R1, and R2) and short-term (BASE, FU1, FU2, and FU3) responses to exercise. β-CTX, P1NP, and IL-6 responses to exercise were significantly lower in the immediate postexercise period with CHO feeding compared with PBO (β-CTX: P = 0.028; P1NP: P = 0.021; IL-6: P = 0.036), although there was no difference in the short-term response (β-CTX: P = 0.856; P1NP: P = 0.721; IL-6: P = 0.327). No other variable was significantly affected by CHO feeding during exercise. We conclude that CHO feeding during exercise attenuated the β-CTX and P1NP responses in the hours but not days following exercise, indicating an acute effect of CHO feeding on bone turnover.

Objectives: This study aimed to assess how menstrual cycle phase and extended menstrual cycle length influence the incidence of injuries in international footballers.Methods: Over a 4-year period, injuries from England international footballers at training camps or matches were recorded, alongside self-reported information on menstrual cycle characteristics at the point of injury. Injuries in eumenorrheic players were categorized into early follicular, late follicular, or luteal phase. Frequencies were also compared between injuries recorded during the typical cycle and those that occurred after the cycle would be expected to have finished. Injury incidence rates (per 1,000 person days) and injury incidence rate ratios were calculated for each phase for all injuries and injuries stratified by type.Results: One hundred fifty-six injuries from 113 players were eligible for analysis. Injury incidence rates per 1,000 person-days were 31.9 in the follicular, 46.8 in the late follicular, and 35.4 in the luteal phase, resulting in injury incidence rate ratios of 1.47 (Late follicular:Follicular), 1.11 (Luteal:Follicular), and 0.76 (Luteal:Late follicular). Injury incident rate ratios showed that muscle and tendon injury rates were 88% greater in the late follicular phase compared to the follicular phase, with muscle rupture/tear/strain/cramps and tendon injuries/ruptures occurring over twice as often during the late follicular phase compared to other phases 20% of injuries were reported as occurring when athletes were “overdue” menses.Conclusion: Muscle and tendon injuries occurred almost twice as often in the late follicular phase compared to the early follicular or luteal phase. Injury risk may be elevated in typically eumenorrheic women in the days after their next menstruation was expected to start.

Objectives To determine the incidence and characteristics of injury and illness in English men’s and women’s senior and youth international football. Methods Time-loss injuries and illnesses, alongside match and training exposure, were collected across 8 seasons (2012–2020) in youth (U15, U16, U17, U18, U19) and senior (U20, U21, U23, senior) English men’s and women’s international teams. Analysis of incidence, burden, and severity of injury and illness was completed. Sex-specific comparisons were made between the senior and youth groups, and across the 8 seasons of data collection. Results In men’s international football, 535 injuries were recorded (216 senior; 319 youth) during 73,326 h of exposure. Overall, match injury incidence (31.1 ± 10.8 injuries/1000 h) and burden (454.0 ± 195.9 d absent/1000 h) were greater than training injury incidence (4.0 ± 1.0 injuries/1000 h) and burden (51.0 ± 21.8 d absent/1000 h) (both P < 0.001). In women’s international football, 503 injuries were recorded (senior: 177; youth: 326) during 80,766 h of exposure and match injury incidence (27.6 ± 11.3 injuries/1000 h) and burden (506.7 ± 350.2 days absent/1000 h) were greater than training injury incidence (5.1 ± 1.8 injuries/1000 h) and burden (87.6 ± 32.8 days absent/1000 h) (both P < 0.001). In women’s international football, a group × season interaction was observed for training injury incidence (P = 0.021), with the senior group recording a greater training injury incidence during the 2015–2016 season compared to the youth group (14.4 vs 5.7 injuries/1000 h; P = 0.022). There was no difference in injury severity between match and training for men’s (P = 0.965) and women’s (P = 0.064) international football. Conclusions The findings provide a comprehensive examination of injury and illness in English men’s and women’s senior and youth international football. Practitioners will be able to benchmark their team’s injury and illness incidence and characteristics to the match-play and training information provided in the present study.

Habitual football participation has been shown to be osteogenic, although the specific volume of football participation required to cause bone adaptations are not well established. The aim of the present study is to investigate tibial bone adaptations in response to 12 weeks of increased training volume in elite adolescents who are already accustomed to irregular impact training. 99 male adolescent elite footballers participated (age 16±0 y; height 1.76±0.66 m; body mass 70.2±8.3 kg). Tibial scans were performed using peripheral quantitative computed tomography immediately before and 12 weeks after an increase in football training volume. Scans were obtained at 4, 14, 38 and 66% of tibial length. Trabecular density (mg/cm), cortical density (mg/cm), cross-sectional area, cortical area (mm), cortical thickness (mm) and strength strain index (mm) were assessed. Trabecular (4%) and cortical density (14, 38%), cortical cross-sectional area (14, 38%), total cross-sectional area (66%), cortical thickness (14, 38%) and strength strain index (14, 38%) increased following 12 weeks of augmented volume training (P<0.05). Increased density of trabecular and cortical compartments and cortical thickening were shown following an increased volume of training. These adaptive responses may have been enhanced by the adolescent status of the cohort, supporting the role of early exercise intervention in improving bone strength.

Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations.Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes.Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays.Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05). Conclusions:The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions.