Bone mineral density (BMD) is the most important predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry. We tested the top-associated BMD markers for replication in 50,933 independent subjects and for risk of low-trauma fracture in 31,016 cases and 102,444 controls. We identified 56 loci (32 novel)associated with BMD atgenome-wide significant level (P<5×10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal-stem-cell differentiation, endochondral ossification and the Wnt signalling pathways. However, we also discovered loci containing genes not known to play a role in bone biology. Fourteen BMD loci were also associated with fracture risk (P<5×10−4, Bonferroni corrected), of which six reached P<5×10−8 including: 18p11.21 (C18orf19), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Effects of 6 mo of heavy-resistance training combined with explosive exercises on neural activation of the agonist and antagonist leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris, as well as maximal and explosive strength were examined in 10 middle-aged men (M40; 42 +/- 2 yr), 11 middle-aged women (W40; 39 +/- 3 yr), 11 elderly men (M70; 72 +/- 3 yr) and 10 elderly women (W70; 67 +/- 3 yr). Maximal and explosive strength remained unaltered during a 1-mo control period with no strength training. After the 6 mo of training, maximal isometric and dynamic leg-extension strength increased by 36 +/- 4 and 22 +/- 2% (P < 0. 001) in M40, by 36 +/- 3 and 21 +/- 3% (P < 0.001) in M70, by 66 +/- 9 and 34 +/- 4% (P < 0.001) in W40, and by 57 +/- 10 and 30 +/- 3% (P < 0.001) in W70, respectively. All groups showed large increases (P < 0.05-0.001) in the maximum integrated EMGs (iEMGs) of the agonist vastus lateralis and medialis. Significant (P < 0.05-0.001) increases occurred in the maximal rate of isometric force production and in a squat jump that were accompanied with increased (P < 0.05-0. 01) iEMGs of the leg extensors. The iEMG of the antagonist biceps femoris muscle during the maximal isometric leg extension decreased in both M70 (from 24 +/- 6 to 21 +/- 6%; P < 0.05) and in W70 (from 31 +/- 9 to 24 +/- 4%; P < 0.05) to the same level as recorded for M40 and W40. The CSA of the quadriceps femoris increased in M40 by 5% (P < 0.05), in W40 by 9% (P < 0.01), in W70 by 6% (P < 0.05), and in M70 by 2% (not significant). Great training-induced gains in maximal and explosive strength in both middle-aged and elderly subjects were accompanied by large increases in the voluntary activation of the agonists, with significant reductions in the antagonist coactivation in the elderly subjects. Because the enlargements in the muscle CSAs in both middle-aged and elderly subjects were much smaller in magnitude, neural adaptations seem to play a greater role in explaining strength and power gains during the present strength-training protocol.

The purpose of this study was to investigate effects of concurrent strength and endurance training (SE) (2 plus 2 days a week) versus strength training only (S) (2 days a week) in men [SE: n=11; 38 (5) years, S: n=16; 37 (5) years] over a training period of 21 weeks. The resistance training program addressed both maximal and explosive strength components. EMG, maximal isometric force, 1 RM strength, and rate of force development (RFD) of the leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF) throughout the lengths of 4/15-12/15 (L(f)) of the femur, muscle fibre proportion and areas of types I, IIa, and IIb of the vastus lateralis (VL), and maximal oxygen uptake (VO(2max)) were evaluated. No changes occurred in strength during the 1-week control period, while after the 21-week training period increases of 21% (p<0.001) and 22% (p<0.001), and of 22% (p<0.001) and 21% (p<0.001) took place in the 1RM load and maximal isometric force in S and SE, respectively. Increases of 26% (p<0.05) and 29% (p<0.001) occurred in the maximum iEMG of the VL in S and SE, respectively. The CSA of the QF increased throughout the length of the QF (from 4/15 to 12/15 L(f)) both in S (p<0.05-0.001) and SE (p<0.01-0.001). The mean fibre areas of types I, IIa and IIb increased after the training both in S (p<0.05 and 0.01) and SE (p<0.05 and p<0.01). S showed an increase in RFD (p<0.01), while no change occurred in SE. The average iEMG of the VL during the first 500 ms of the rapid isometric action increased (p<0.05-0.001) only in S. VO(2max) increased by 18.5% (p<0.001) in SE. The present data do not support the concept of the universal nature of the interference effect in strength development and muscle hypertrophy when strength training is performed concurrently with endurance training, and the training volume is diluted by a longer period of time with a low frequency of training. However, the present results suggest that even the low-frequency concurrent strength and endurance training leads to interference in explosive strength development mediated in part by the limitations of rapid voluntary neural activation of the trained muscles.

Eleven male subjects (20-32 years) accustomed to strength training went through progressive, high-load strength training for 24 weeks with intensities ranging variably between 70 and 120% during each month. This training was also followed by a 12-week detraining period. An increase of 26.8% (P less than 0.001) in maximal isometric strength took place during the training. The increase in strength correlated (P less than 0.05) with significant (P less than 0.05-0.01) increases in the neural activation (IEMG) of the leg extensor muscles during the most intensive training months. During the lower-intensity training, maximum IEMG decreased (P less than 0.05). Enlargements of muscle-fibre areas, especially of fast-twitch type (P less than 0.001), took place during the first 12 weeks of training. No hypertrophic changes were noted during the latter half of training. After initial improvements (P less than 0.05) no changes or even slight worsening were noted in selected force-time parameters during later strength training. During detraining a great (P less than 0.01) decrease in maximal strength was correlated (P less than 0.05) with the decrease (P less than 0.05) in the maximum IEMGs of the leg extensors. This period resulted also in decreases (P less than 0.05) of the mean muscle-fibre areas of both fibre types. It was concluded that improvement in strength may be accounted for by neural factors during the course of very intensive strength training. Selective training-induced hypertrophy also contributed to strength development but muscle hypertrophy may have some limitations during long-lasting strength training, especially in highly trained subjects.

Hormonal and neuromuscular adaptations to strength training were studied in eight male strength athletes (SA) and eight non-strength athletes (NA). The experimental design comprised a 21-week strength-training period. Basal hormonal concentrations of serum total testosterone (T), free testosterone (FT) and cortisol (C) and maximal isometric strength, right leg 1 repetition maximum (RM) of the leg extensors were measured at weeks 0, 7, 14 and 21. Muscle cross-sectional area (CSA) of the quadriceps femoris was measured by magnetic resonance imaging (MRI) at weeks 0 and 21. In addition, the acute heavy resistance exercises (AHRE) (bilateral leg extension, five sets of ten RM, with a 2-min rest between sets) including blood samples for the determination of serum T, FT, C, and GH concentrations were assessed before and after the 21-week training. Significant increases of 20.9% in maximal force and of 5.6% in muscle CSA in NA during the 21-week strength training period were greater than those of 3.9% and -1.8% in SA, respectively. There were no significant changes in serum basal hormone concentrations during the 21-week experiment. AHRE led to significant acute decreases in isometric force and acute increases in serum hormones both at weeks 0 and 21. Basal T concentrations (mean of 0, 7, 14 and 21 weeks) and changes in isometric force after the 21-week period correlated with each other (r=0.84, P<0.01) in SA. The individual changes in the acute T responses between weeks 0 and 21 and the changes in muscle CSA during the 21-week training correlated with each other (r=0.76, P<0.05) in NA. The correlations between T and the changes in isometric strength and in muscle CSA suggest that both serum basal testosterone concentrations and training-induced changes in acute testosterone responses may be important factors for strength development and muscle hypertrophy.