Is hip morphology a risk factor for developing hip osteoarthritis? A systematic review with meta-analysis.

OBJECTIVE: To appraise the highest evidence on hip morphology as a risk factor for developing hip osteoarthritis (OA). DESIGN: We searched for studies evaluating the association between radiological hip morphology parameters and the prevalence, incidence or progression of hip OA (based on different radiographic and clinical criteria) in the MEDLINE, EMBASE, Web of Science, Scopus, Cochrane Library and PEDro databases from inception until June 2020. Prospective and cross-sectional studies were separately evaluated. Data are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We included 9 prospective and 21 cross-sectional studies in the meta-analysis, and evaluated 42,831 hips from 25,898 individuals (mean age: 59 years). Prospective studies showed that, compared with control hips, hips with cam morphology (alpha angle >60°; OR = 2.52, 95% CI: 1.83 to 3.46, P < 0.001) or hip dysplasia (lateral center-edge angle (LCEA) <25°; OR = 2.38, 95% CI: 1.84 to 3.07, P < 0.001), but not hips with pincer morphology (LCEA >39°; OR = 1.08, 95% CI: 0.57 to 2.07, P = 0.810), were more likely to develop hip OA than hips without these morphologies. Cross-sectional studies showed a greater prevalence of pincer morphology (LCEA >39°, OR = 3.71, 95% CI: 2.98 to 4.61, P < 0.001) and acetabular retroversion (crossover sign; OR = 2.65, 95% CI: 1.17 to 6.03, P = 0.020) in hips with OA than in control hips. CONCLUSION: Cam morphology and hip dysplasia were consistently associated with the development of hip OA. Pincer morphology was associated with hip OA in cross-sectional but not in prospective studies. The heterogeneous quantification of pincer morphology on radiographs limits a clear conclusion on its association with hip OA.

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review.

OBJECTIVE: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. DESIGN: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. RESULTS: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). CONCLUSIONS: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.

Early vs. late rate of torque development: Relation with maximal strength and influencing factors.

We re-examined the relationship between rate of torque development (RTD) and maximal voluntary contractions (MVC) torque, and investigated some possible neuromuscular determinants of early (≤100 ms) and late (≥200 ms) RTD. Seventeen healthy men performed maximal explosive isometric knee extensions at five joint angles, from which MVC torque, RTD at different time intervals (50-250 ms), and early quadriceps EMG activity (EMG50) were evaluated. Quadriceps muscle thickness (MT) was quantified by longitudinal ultrasonography. The relationship between MVC torque, EMG50 and MT against RTD was assessed with Pearson's and repeated measures correlation coefficients. Moderate-to-strong correlation coefficients were observed between MVC torque and RTD (r = 0.50-0.88, p < 0.001), with stronger relationships for late RTD than for early RTD. Weak-to-strong correlation coefficients were observed amongst RTD and EMG50 (r = 0.37-0.83, p < 0.001), with stronger relationships for early RTD than for late RTD. Only late RTD was significantly correlated with MT, though only moderately (r = 0.50-0.52, p < 0.05). These findings suggest that early and late knee extension RTD are potentially governed by different neuromuscular factors. Neuromuscular activation seems to have a greater influence on early RTD than on late RTD, and vice versa for muscle mass.

Factors influencing bilateral deficit and inter-limb asymmetry of maximal and explosive strength: motor task, outcome measure and muscle group.

PURPOSE: The purpose of the present study was to investigate the influence of strength outcome [maximal voluntary contraction (MVC) torque vs. rate of torque development (RTD)], motor task (unilateral vs. bilateral) and muscle group (knee extensors vs. flexors) on the magnitude of bilateral deficits and inter-limb asymmetries in a large heterogeneous group of athletes. METHODS: 259 professional/semi-professional athletes from different sports (86 women aged 21 ± 6 years and 173 men aged 20 ± 5 years) performed unilateral and bilateral "fast and hard" isometric maximal voluntary contractions of the knee extensors and flexors on a double-sensor dynamometer. Inter-limb asymmetries and bilateral deficits were compared across strength outcomes (MVC torque and multiple RTD measures), motor tasks and muscle groups. RESULTS: Most RTD outcomes showed greater bilateral deficits than MVC torque for knee extensors, but not for knee flexors. Most RTD outcomes, not MVC torque, showed higher bilateral deficits for knee extensors compared to knee flexors. For both muscle groups, all RTD measures resulted in higher inter-limb asymmetries than MVC torque, and most RTD measures resulted in greater inter-limb asymmetries during unilateral compared to bilateral motor tasks. CONCLUSIONS: The results of the present study highlight the importance of outcome measure, motor task and muscle group when assessing bilateral deficits and inter-limb asymmetries of maximal and explosive strength. Compared to MVC torque and bilateral tasks, RTD measures and unilateral tasks could be considered more sensitive for the assessment of bilateral deficits and inter-limb asymmetries in healthy professional/semi-professional athletes.

Deficits in rate of torque development are accompanied by activation failure in patients with knee osteoarthritis.

Aim of this study was to investigate if knee extensor maximal voluntary contraction (MVC) torque and rate of torque development (RTD) deficits are accompanied by neuromuscular activation failure in patients with knee osteoarthritis (KOA). Nineteen patients with unilateral KOA completed gradual MVCs, from which MVC torque, voluntary activation and maximal EMG activity were recorded, and explosive MVCs, from which RTD and rate of EMG rise were recorded. For gradual MVCs, MVC torque (-28%), voluntary activation (-6%) and maximal EMG activity (-30%) were lower on the involved than on the uninvolved side (p < 0.001). Asymmetries in MVC torque and maximal EMG activity were positively correlated (r = 0.70; p < 0.001). For explosive MVCs, involved-side RTD (-19%) and rate of EMG rise (-20%) were lower compared to the uninvolved side (p < 0.05-0.001). Asymmetries in RTD and rate of EMG rise were positively correlated (r = 0.61-0.80; p < 0.01). Deficits in isometric knee extensor strength were accompanied by neuromuscular activation failure during gradual MVCs and, more importantly, during the early phase of explosive MVCs. Such inability to rapidly activate the quadriceps may have functional consequences and warrants greater attention in the evaluation and rehabilitation of patients with KOA.

Reproducibility and validity of the Italian version of the International Physical Activity Questionnaire in obese and diabetic patients.

PURPOSE: Aims of this study were to evaluate the agreement between the short and long versions of the International Physical Activity Questionnaire (IPAQ: Italian versions), their reproducibility (agreement and reliability) and construct validity (relative to pedometry) in a clinical population. METHODS: Ninety patients affected by obesity (N = 39), type 2 diabetes mellitus (N = 26) or both (N = 25) were recruited. They were asked to maintain their usual physical activity habits during two consecutive weeks and to fill the questionnaires twice (at the end of each week). They were also asked to wear a pedometer for 7 consecutive days after the first administration of the questionnaires. RESULTS: We found acceptable agreement between the IPAQ short and long versions (ICC2,1 values were 0.81 and 0.77 for the 1st and 2nd administration), uncertain reproducibility (acceptable reliability but poor agreement) and inadequate validity relative to pedometry (the correlation coefficients between all IPAQ scores and daily steps were <0.50) for both IPAQ short and IPAQ long. CONCLUSIONS: The IPAQ use may be justified in daily clinical practice and in clinical research (e.g., in cross-sectional studies) for a simple and rapid evaluation of the physical activity level for discriminative purposes. However, the use of these questionnaires does not appear suitable for prospective interventional studies in which the level of physical activity of the recruited patients has to be assessed over time.

Direct and crossed effects of somatosensory electrical stimulation on motor learning and neuronal plasticity in humans.

PURPOSE: Sensory input can modify voluntary motor function. We examined whether somatosensory electrical stimulation (SES) added to motor practice (MP) could augment motor learning, interlimb transfer, and whether physiological changes in neuronal excitability underlie these changes. METHODS: Participants (18-30 years, n = 31) received MP, SES, MP + SES, or a control intervention. Visuomotor practice included 300 trials for 25 min with the right-dominant wrist and SES consisted of weak electrical stimulation of the radial and median nerves above the elbow. Single- and double-pulse transcranial magnetic stimulation (TMS) metrics were measured in the intervention and non-intervention extensor carpi radialis. RESULTS: There was 27 % motor learning and 9 % (both p < 0.001) interlimb transfer in all groups but SES added to MP did not augment learning and transfer. Corticospinal excitability increased after MP and SES when measured at rest but it increased after MP and decreased after SES when measured during contraction. No changes occurred in intracortical inhibition and facilitation. MP did not affect the TMS metrics in the transfer hand. In contrast, corticospinal excitability strongly increased after SES with MP + SES showing sharply opposite of these effects. CONCLUSION: Motor practice and SES each can produce motor learning and interlimb transfer and are likely to be mediated by different mechanisms. The results provide insight into the physiological mechanisms underlying the effects of MP and SES on motor learning and cortical plasticity and show that these mechanisms are likely to be different for the trained and stimulated motor cortex and the non-trained and non-stimulated motor cortex.

Direct and crossed effects of somatosensory stimulation on neuronal excitability and motor performance in humans.

This analytic review reports how prolonged periods of somatosensory electric stimulation (SES) with repetitive transcutaneous nerve stimulation can have 'direct' and 'crossed' effects on brain activation, corticospinal excitability, and motor performance. A review of 26 studies involving 315 healthy and 78 stroke and dystonia patients showed that the direct effects of SES increased corticospinal excitability up to 40% (effect size: 0.2 to 6.1) and motor performance up to 14% (effect size: 0.3 to 3.1) but these two features did not correlate. SES did not affect measures of intracortical excitability. Most likely, a long-term potentiation-like mechanism in the excitatory glutamatergic connections between the primary sensory and motor cortices mediates the direct effects of SES on corticospinal excitability and motor performance. We propose two models for the untested hypothesis that adding SES to unilateral motor practice could magnify the magnitude of inter-limb transfer. If tenable, the hypothesis would expand the evolving repertoire of sensory augmentation of cross-education using mirrors and add SES as an alternative to conventional rehabilitation strategies such as constraint-induced movement therapy.

Validity of resting myotonometric assessment of lower extremity muscles in chronic stroke patients with limited hypertonia: a preliminary study.

The aim of this preliminary study was to examine the validity of a recently-introduced tool (MyotonPRO) for the assessment of mechanical parameters of the main lower extremity muscles in patients with chronic stroke. Thigh and shank muscles of 20 stroke patients with limited hypertonia (11 men and 9 women; mean age: 52±11yrs) and 20 healthy controls (11 men and 9 women; mean age: 53±10yrs) were bilaterally evaluated with (i) MyotonPRO for muscle stiffness, tone and elasticity, (ii) ultrasonography for muscle and subcutaneous thickness, and (iii) dynamometry for isometric muscle strength. MyotonPRO parameters of stroke patients were reassessed a week later (inter-day test-retest design). For all the investigated muscles, MyotonPRO variables did not differ between the more affected and the less affected side of patients (P>0.05 for main side effect), and neither differed between patients and controls (P>0.05 for main group effect), except for gastrocnemius medialis stiffness that was higher in patients (300±51N/m) than in controls (281±29N/m; P<0.05). Thigh muscle stiffness was negatively correlated to subcutaneous thickness (r=-0.84 for the vastus lateralis; P<0.001), while only tibialis anterior stiffness and tone correlated positively with muscle thickness (both r=0.46; P<0.01). Test-retest reliability of MyotonPRO parameters was adequate, except for muscle elasticity. The validity of MyotonPRO for the evaluation of thigh muscles in chronic stroke patients is partially challenged by the poor discriminant ability and by the considerable impact of subcutaneous tissue thickness (sex-dependent) on mechanical parameters. The potential validity of MyotonPRO for the assessment of shank muscles requires further investigation.

Differences in proprioception, muscle force control and comfort between conventional and new-generation knee and ankle orthoses.

The aim of this study was to compare muscle force control and proprioception between conventional and new-generation experimental orthoses. Sixteen healthy subjects participated in a single-blind controlled trial in which two different types of orthosis were applied to the dominant knee or ankle, while the following variables were evaluated: muscle force control (accuracy), joint position sense, kinesthesia, static balance as well as subjective outcomes. The use of experimental orthoses resulted in better force accuracy during isometric knee extensions compared to conventional orthoses (P=0.005). Moreover, the use of experimental orthoses resulted in better force accuracy during concentric (P=0.010) and eccentric (P=0.014) ankle plantar flexions and better knee joint kinesthesia in the flexed position (P=0.004) compared to conventional orthoses. Subjective comfort (P<0.001) and preference scores were higher with experimental orthoses compared to conventional ones. In conclusion, orthosis type affected static and dynamic muscle force control, kinesthesia, and perceived comfort in healthy subjects. New-generation experimental knee and ankle orthoses may thus be recommended for prophylactic joint bracing during physical activity and to improve the compliance for orthosis use, particularly in patients who require long-term bracing.

Assessment of quadriceps muscle weakness in patients after total knee arthroplasty and total hip arthroplasty: methodological issues.

The aim of this exploratory study was to verify whether the evaluation of quadriceps muscle weakness is influenced by the testing modality (isometric vs. isokinetic vs. isoinertial) and by the calculation method (within-subject vs. between-subject comparisons) in patients 4-8months after total knee arthroplasty (TKA, n=29) and total hip arthroplasty (THA, n=30), and in healthy controls (n=19). Maximal quadriceps strength was evaluated as (1) the maximal voluntary contraction (MVC) torque during an isometric contraction, (2) the peak torque during an isokinetic contraction, and (3) the one repetition maximum (1-RM) load during an isoinertial contraction. Muscle weakness was calculated as the difference between the involved and the uninvolved side (within-subject comparison) and as the difference between the involved side of patients and controls (between-subject comparison). Muscle weakness estimates were not significantly affected by the calculation method (within-subject vs. between-subject; P>0.05), whereas a significant main effect of testing modality (P<0.05) was observed. Isometric MVC torque provided smaller weakness estimates than isokinetic peak torque (P=0.06) and isoinertial 1-RM load (P=0.008), and the clinical occurrence of weakness (proportion of patients with large strength deficits) was also lower for MVC torque. These results have important implications for the evaluation of quadriceps muscle weakness in TKA and THA patients 4-8months after surgery.

Validity and reliability of isometric, isokinetic and isoinertial modalities for the assessment of quadriceps muscle strength in patients with total knee arthroplasty.

Reliability of isometric, isokinetic and isoinertial modalities for quadriceps strength evaluation, and the relation between quadriceps strength and physical function was investigated in 29 total knee arthroplasty (TKA) patients, with an average age of 63 years. Isometric maximal voluntary contraction torque, isokinetic peak torque, and isoinertial one-repetition maximum load of the involved and uninvolved quadriceps were evaluated as well as objective (walking parameters) and subjective physical function (WOMAC). Reliability was good and comparable for the isometric, isokinetic, and isoinertial strength outcomes on both sides (intraclass correlation coefficient range: 0.947-0.966; standard error of measurement range: 5.1-9.3%). Involved quadriceps strength was significantly correlated to walking speed (r range: 0.641-0.710), step length (r range: 0.685-0.820) and WOMAC function (r range: 0.575-0.663), independent from the modality (P < 0.05). Uninvolved quadriceps strength was also significantly correlated to walking speed (r range: 0.413-0.539), step length (r range: 0.514-0.608) and WOMAC function (r range: 0.374-0.554) (P < 0.05), except for WOMAC function/isokinetic peak torque (P > 0.05). In conclusion, isometric, isokinetic, and isoinertial modalities ensure valid and reliable assessment of quadriceps muscle strength in TKA patients.

Hip flexor muscle fatigue in patients with symptomatic femoroacetabular impingement.

PURPOSE: Patients with symptomatic femoroacetabular impingement (FAI) have considerable hip muscle weakness, in particular, hip flexion and hip adduction. In addition, they experience disabilities while performing prolonged dynamic tasks. It was therefore postulated that, besides hip flexor muscle weakness, patients with symptomatic FAI would show greater hip flexor fatigue compared with healthy controls. METHODS: Hip flexor fatigue was evaluated in two different experiments. Fifteen patients with symptomatic FAI and 15 age-matched healthy controls were tested in each experiment. In the first one, changes in hip flexor torque fluctuations and electromyographic (EMG) activity were measured during a sustained submaximal isometric contraction. In the second experiment, hip flexor torque decline was measured during a series of 20 maximal dynamic contractions. RESULTS: Patients with FAI exhibited hip flexor weakness under both isometric (P = 0.02) and isokinetic conditions (P = 0.03). Fatigue-induced changes in isometric hip flexor torque fluctuations, EMG root mean square and median frequency did not differ significantly between patients and controls (P > 0.05). Similarly, isokinetic hip flexor torque decline was comparable in patients with FAI and controls (P > 0.05). CONCLUSIONS: None of the hip flexor fatigue outcomes considered here differed between patients with symptomatic FAI and controls. Therefore, the disabilities that patients experience while performing prolonged dynamic tasks do not seem to be caused by exaggerated hip flexor muscle fatigue.

Hip muscle weakness in patients with symptomatic femoroacetabular impingement.

OBJECTIVE: Femoroacetabular impingement (FAI) is a pathomechanical process, which may cause hip pain, disability and early development of hip osteoarthritis (OA) in young and active adults. Patients with FAI experience functional disability during dynamic weight-bearing activities, which could originate from weakness of the hip muscles. The objective of this study was to compare hip muscle strength between patients with symptomatic FAI and healthy controls. It was hypothesized that patients would present overall hip muscle weakness compared to controls. METHODS: A total of 22 FAI patients and 22 controls matched for gender, age, and body mass participated in the study. We evaluated isometric maximal voluntary contraction (MVC) strength of all hip muscle groups using hand-held and isokinetic dynamometry, and electromyographic (EMG) activity of the rectus femoris (RF) and tensor fasciae latae (TFL) muscles during active flexion of the hip. RESULTS: FAI patients had significantly lower MVC strength than controls for hip adduction (28%), flexion (26%), external rotation (18%) and abduction (11%). TFL EMG activity was significantly lower in FAI patients compared with controls (P=0.048), while RF EMG activity did not differ significantly between the two groups (P=0.056). CONCLUSIONS: Patients with symptomatic FAI presented muscle weakness for all hip muscle groups, except for internal rotators and extensors. Based on EMG recordings, it was demonstrated that patients with symptomatic FAI have a reduced ability to activate TFL muscle during hip flexion. These findings provide orthopedic surgeons with objective information about the amount and specificity of hip muscle weakness in patients with FAI. Future research should investigate the relationship between hip muscle weakness, functional disability and overuse injury risks, as well as the effects of hip muscle strengthening on clinical outcomes in individuals with symptomatic FAI.

GH responses to two consecutive bouts of whole body vibration, maximal voluntary contractions or vibration alternated with maximal voluntary contractions administered at 2-h intervals in healthy adults.

BACKGROUND: Pharmacological or exercise stimuli repeated at a short interval (but not electrical muscle stimulation) are associated with a blunting of GH responsiveness. AIM: To compare GH responses to repeated bout of three different GH-releasing stimuli. METHODS: The effects of two consecutive bouts (with a 2-h interval) of whole body vibrations (WBV), maximal voluntary contractions alone (MVC), or alternated with WBV (MVC-WBV) on blood GH and lactate (LA) were assessed in nine young males. RESULTS: Baseline levels of both GH and LA increased significantly after the first bout of all the tested stimuli, and were significantly lower after WBV than after MVC or MVC alternated with WBV, no difference being detected between these last. The administration of a second bout resulted in significantly lower GH increases than those elicited in the first bout in the three different tests; significantly lower LA responses were recorded after the second bout of MVC and MVC-WBV when compared with those obtained after the first bout, while no significant differences were observed after the two WBV bouts for LA. All responses after the second bout of MVC and MVC-WBV were significantly higher than those observed after WBV alone. GH concentrations were significantly correlated with LA after all stimuli, although LA concentrations after the second bout were associated with markedly lower GH levels. CONCLUSIONS: A significant blunting of GH responsiveness ensues after a second bout of different GH-releasing stimuli, independent from the amount of GH released after the first bout. This is a pattern also observed for other pharmacological stimuli and exercise modalities, and suggests a common mechanism underlying different GH-releasing stimuli.

Differences in twitch potentiation between voluntary and stimulated quadriceps contractions of equal intensity.

This study compared the extent of twitch and M-wave potentiation (POT) between voluntary and stimulated quadriceps contractions performed at the same intensity. Sixteen healthy men completed 10-s isometric knee extensions at 40% of the maximal voluntary contraction torque under electrical stimulation and voluntary conditions. Single stimuli were delivered to the femoral nerve to evoke twitches before (PRE) and from 3 to 600 s after the end of each conditioning contraction. Changes in twitch contractile properties and M-wave characteristics were compared between the conditions. The extent of twitch peak torque POT was smaller for the stimulated (122+/-20% of PRE) than for the voluntary condition (133+/-20% of PRE). The magnitude of POT for the maximal rate of twitch torque development was also smaller for the stimulated trial. Rectus femoris M-wave amplitude was potentiated by the voluntary but not by the stimulated contraction. It was concluded that stimulated contractions resulted in smaller twitch and M-wave POT than voluntary contractions, despite equivalent torque output and duration. The spatially and temporally fixed recruitment of motor units with electrical stimulation and therefore the lower number of activated motor units compared with voluntary actions of equal intensity could explain the present findings.

Soleus T reflex modulation in response to spinal and tendinous adaptations to unilateral lower limb suspension in humans.

AIM: To investigate the influence of tendinous and synaptic changes induced by unilateral lower limb suspension (ULLS) on the tendon tap reflex. METHODS: Eight young men underwent a 23-day period of ULLS. Muscle cross-sectional area (CSA), torque and electromyographic (EMG) activity of the plantar flexor muscles (normalized to the M wave), Achilles tendon-aponeurosis mechanical properties, soleus (SOL) H and T reflexes and associated peak twitch torques were measured at baseline, after 14 and 23 days of ULLS, and 1 week after resuming ambulatory activity. RESULTS: Significant decreases in muscle CSA (-9%), in maximal voluntary torque (-10%) and in the associated SOL EMG activity (-16%) were found after ULLS (P < 0.05). In addition to a 36% (P < 0.01) decrease in tendon-aponeurosis stiffness, normalized H reflex increased by 35% (P < 0.05). An increase in the slope (28%, P < 0.05) and intercept (85%, P < 0.05) of the T reflex recruitment curve pointed to an increase in the gain and to a decrease in the sensitivity of this reflex, possibly resulting from the decrease in the tendon-aponeurosis stiffness at low forces. Following ULLS, changes in tendinous stiffness correlated with changes in neuromuscular efficiency (peak twitch torque to reflex ratio) at higher tendon tap forces. CONCLUSION: These findings point out the dual and antagonistic influences of spinal and tendinous adaptations upon the tendon tap reflex in humans under conditions of chronic unloading. These observations have potential implications for the sensitivity of the short-latency Ia stretch response involved in rapid compensatory contractions to unexpected postural perturbations.

GH responses to two consecutive bouts of neuromuscular electrical stimulation in healthy adults.

BACKGROUND: It is well established that repeated GHRH administration or repeated voluntary exercise bouts are associated with a complete blunting of GH responsiveness when the administration of the second stimulus follows the first one after a 2-h interval. AIM: To evaluate GH responses to neuromuscular electrical stimulation (NMES) in healthy adults. METHODS: Six volunteers (mean age+/-s.d. 31.7+/-5.5 years) were studied before and after two consecutive bouts of NMES exercise (a series of 20 contractions at the maximum of individual tolerance, frequency: 75 Hz, pulse duration: 400 mus, on-off ratio: 6.25-20 s) administered at a 2-h interval. RESULTS: Baseline GH levels (mean: 0.3+/-0.2 ng/ml) significantly increased after the first NMES (peak: 4.2+/-3.7 ng/ml), with a complete normalization after 120 min (0.3+/-0.3 ng/ml). The administration of the second bout of NMES of comparable characteristics also resulted in a significant GH increase (peak: 5.2+/-3.2 ng/ml), which was comparable with that observed after the previous one. GH net incremental area under the curve after the first and second bouts of NMES were not significantly different (155.1+/-148.5 and 176.9+/-123.3 ng/ml per h, P=0.785). CONCLUSIONS: Unlike repeated pharmacological stimuli and voluntary exercise bouts, subsequent sessions of NMES administered at a 2-h interval appear to circumvent feedback mechanisms and to re-induce the GH responses, thus indicating a possible different underlying mechanism elicited by different GH-releasing stimuli.