Exploring neuronal mechanisms of osteosarcopenia in older adults.

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight-bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing-related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults.

Postsynaptic potentials of soleus motor neurons produced by transspinal stimulation: a human single-motor unit study.

Transspinal (or transcutaneous spinal cord) stimulation is a noninvasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and nonsomatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single-pulse transspinal stimulation using single-motor unit (SMU) discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit. Peristimulus time histogram, peristimulus frequencygram, and surface electromyography (sEMG) were used to characterize the postsynaptic potentials of soleus motor neurons. Transspinal stimulation produced short-latency excitatory postsynaptic potentials (EPSPs) followed by two distinct phases of inhibitory postsynaptic potentials (IPSPs) in most soleus motor neurons and only IPSPs in others. Transspinal stimulation generated double discharges at short interspike intervals in a few motor units. The short-latency EPSPs were likely mediated by muscle spindle group Ia and II afferents, and the IPSPs via excitation of group Ib afferents and recurrent collaterals of motor neurons leading to activation of diverse spinal inhibitory interneuronal circuits. Further studies are warranted to understand better how transspinal stimulation affects depolarization of α motor neurons over multiple spinal segments. This knowledge will be seminal for developing effective transspinal stimulation protocols in upper motor neuron lesions.NEW & NOTEWORTHY Transspinal stimulation produces distinct actions on soleus motor neurons: an early short-latency excitation followed by two inhibitions or only inhibition and doublets. These results show how transspinal stimulation affects depolarization of soleus α motor neurons in healthy humans.

Whole body vibration activates the tonic vibration reflex during voluntary contraction.

[Purpose] The beneficial neuromuscular effects of whole-body vibration are explained by the tonic vibration or bone myoregulation reflex. Depending on factors that remain undefined, whole-body vibration may activate the tonic vibration or bone myoregulation reflex. We aimed to examine whether voluntary contraction facilitates activation of the tonic vibration reflex during whole-body vibration. [Participants and Methods] Eleven volunteers were included in this study. Local and whole-body vibrations were applied in a quiet standing (without voluntary contraction) and a semi-squatting (isometric soleus contraction) position. Local vibration was applied to the Achilles tendon. Surface electromyography was obtained from the soleus muscle. The cumulative average method was used to determine soleus reflex latency. [Results] In the quiet standing position, the bone myoregulation reflex latency was 39.9 ± 4.1 milliseconds and the tonic vibration reflex latency was 35.4 ± 3.6 milliseconds. Whole-body vibration application in the semi-squatting position activated the tonic vibration reflex in four participants and the bone myoregulation reflex in seven participants. Local vibration activated the tonic vibration reflex in both positions for all participants. [Conclusion] Simultaneous whole-body vibration application and voluntary contraction may activate the tonic vibration reflex. Determining the spinal mechanisms underlying the whole-body vibration exercises will enable their effective and efficient use in rehabilitation and sports.

The reflex mechanism underlying the neuromuscular effects of whole-body vibration: Is it the tonic vibration reflex?

OBJECTIVES: Whole-body vibration (WBV) is applied to the sole of the foot, whereas local mechanical vibration (LMV) is applied directly to the muscle or tendon. The time required for the mechanical stimulus to reach the muscle belly is longer for WBV. Therefore, the WBV-induced muscular reflex (WBV-IMR) latency may be longer than the tonic vibration reflex (TVR) latency. The aim of this study was to determine whether the difference between WBV-IMR and TVR latencies is due to the distance between the vibration application point and the target muscle. METHODS: Eight volunteers participated in this study. The soleus reflex response was recorded during WBV, LMVs, and tendon tap. LMVs were applied to the Achilles tendon and sole of the foot. The latencies were calculated using the cumulative averaging technique. RESULTS: The latency (33.4±2.8 ms) of the soleus reflex induced by the local foot vibration was similar to the soleus TVR latency (30.9±3.2 ms) and T-reflex (32.0±2.4 ms) but significantly shorter than the latency of the soleus WBV-IMR (42.3±3.4 ms) (F(3,21)=27.46, p=0.0001, partial η2=0.797). CONCLUSIONS: The present study points out that the neuronal circuitries of TVR and WBV-IMR are different.

A new method to determine stretch reflex latency.

INTRODUCTION/AIMS: Motion artifact signals (MASs) created by the relative movement of intramuscular wire electrodes are an indicator of the mechanical stimulus arrival time to the muscle belly. This study proposes a method that uses wire electrodes as an intramuscular mechanosensor to determine the stretch reflex (SR) latency without lag time. METHODS: Gastrocnemius SR was induced by tendon tap, heel tap, and forefoot tap. The MASs recorded by intramuscular wire electrodes were extracted from background electromyographic activity using the spike-triggered averaging technique. Simultaneous recordings were obtained from multiple sites to validate the MAS technique. RESULTS: Using intramuscular wire electrodes, the MASs were successfully determined and extracted for all stimulus sites. In the records from the rectus femoris, MASs were also successfully extracted; thus, the reflex latency could be calculated. DISCUSSION: Wire electrodes can be used as an intramuscular mechanosensor to determine the mechanical stimulus arrival time to the muscle belly.

Effect of aging on H-reflex response to fatigue.

Injury as a result of tripping is relatively common among older people. The risk of falling increases with fatigue and of importance is the ability to dorsiflex the foot through timely activation of the tibialis anterior (TA) muscle to ensure the foot clears the ground, or an obstacle, during the swing phase of walking. We, therefore, questioned whether the muscle spindle input to the motoneurons alters with ongoing fatigue in older people. We electrically stimulated the common peroneal nerve to assess the TA primary afferent efficacy using H-reflex before, immediately following and after a fatiguing maximal isometric contraction. M-response was kept unchanged throughout the experiment to ensure a similar stimulus intensity was delivered across time points. H-reflex increased significantly while the TA muscle was in a state of fatigue for the younger participants but tended to decrease with increasing age. The main contributor to the tonicity of TA muscle, i.e., excitatory synapses of spindle primary endings of motoneurons that innervate TA muscle, tend to lose their efficacy during fatigue in the older individuals but increased efficiency in the majority of the younger people. Since TA muscle is the main dorsiflexor of the foot and it needs to be active during the swing phase of stepping to prevent tripping, older individuals become more susceptible to falling when their muscles are fatigued. This finding may help improve devices/treatments to overcome the problem of tripping among older individuals.

Cross-training effect of chronic whole-body vibration exercise: a randomized controlled study.

Purpose: To determine whether unilateral leg whole-body vibration (WBV) strength training induces strength gain in the untrained contralateral leg muscle. The secondary aim was to determine the potential role of spinal neurological mechanisms regarding the effect of WBV exercise on contralateral strength training.Materials and Methods: Forty-two young adult healthy volunteers were randomized into two groups: WBV exercise and Sham control. An isometric semi-squat exercise during WBV was applied regularly through 20 sessions. WBV training was applied to the right leg in the WBV group and the left leg was isolated from vibration. Sham WBV was applied to the right leg of participants in the Control group. Pre- and post-training isokinetic torque and reflex latency of both quadricepses were evaluated.Results: The increase in the strength of right (vibrated) knee extensors was 9.4 ± 10.7% in the WBV group (p = .001) and was 1.2 ± 6.6% in the Control group (p = .724). The left (non-vibrated) extensorsvibrated) knee extensors w4 ± 8.4% in the WBV group (p = .038), whereas it decreased by 1.4 ± 7.0% in the Control (p = .294). The strength gains were significant between the two groups. WBV induced the reflex response of the quadriceps muscle in the vibrated ipsilateral leg and also in the non-vibrated contralateral leg, though with a definite delay. The WBV-induced muscle reflex (WBV-IMR) latency was 22.5 ± 7.7 ms for the vibrated leg and 39.3 ± 14.6 ms for the non-vibrated leg.Conclusions: Chronic WBV training has an effect of the cross-transfer of strength to contralateral homologous muscles. The WBV-induced muscular reflex may have a role in the mechanism of cross-transfer strength.

A stimulus rate that is not influenced by homosynaptic post-activation depression in chronic stroke.

PURPOSE: To determine a stimulus rate that is not influenced by homosynaptic post-activation depression for H-reflex studies in patients with chronic spasticity. MATERIALS AND METHODS: A cohort of 15 chronic stroke patients with soleus spasticity who received inpatient treatment at our rehabilitation centre participated in this study. The effect of stimulus frequency related depression on H-reflex size was tested using four different stimulus rates (0.1, 0.2, 0.3 and 1 Hz). The affected sides stibial nerve was stimulated by a bipolar electrode. The H-reflex was recorded from the affected sideed sidee sidehe affected smine stimulus frequency related depression of H-reflex size, amplitude of the first H-reflex response (H1) was used as control and amplitude of the second H-reflex response (H2) as test. RESULTS: H2 amplitude for frequency of 1 Hz, 0.3 Hz, 0.2 Hz and 0.1 Hz were 74.3, 84.1, 85.5 and 92.7% of H1, respectively. Depression of H2 amplitude was statistically significant for 1 Hz, 0.3 Hz and 0.2 Hz (p < 0.001, p = 0.002, p = 0.024, respectively). CONCLUSIONS: Higher frequency stimulation of Ia afferents than 0.1 Hz induced a stimulus frequency-related depression of H-reflex size in patients with chronic spasticity. The optimal stimulus rate for H-reflex was found to be 0.1 Hz.

Exploring the receptor origin of vibration-induced reflexes.

STUDY DESIGN: An experimental design. OBJECTIVES: The aim of this study was to determine the latencies of vibration-induced reflexes in individuals with and without spinal cord injury (SCI), and to compare these latencies to identify differences in reflex circuitries. SETTING: A tertiary rehabilitation center in Istanbul. METHODS: Seventeen individuals with chronic SCI (SCI group) and 23 participants without SCI (Control group) were included in this study. Latency of tonic vibration reflex (TVR) and whole-body vibration-induced muscular reflex (WBV-IMR) of the left soleus muscle was tested for estimating the reflex origins. The local tendon vibration was applied at six different vibration frequencies (50, 85, 140, 185, 235, and 265 Hz), each lasting for 15 s with 3-s rest intervals. The WBV was applied at six different vibration frequencies (35, 37, 39, 41, 43, and 45 Hz), each lasting for 15 s with 3-s rest intervals. RESULTS: Mean (SD) TVR latency was 39.7 (5.3) ms in the SCI group and 35.9 (2.7) ms in the Control group with a mean (95% CI) difference of -3.8 (-6.7 to -0.9) ms. Mean (SD) WBV-IMR latency was 45.8 (7.4) ms in the SCI group and 43.3 (3.0) ms in the Control group with a mean (95% CI) difference of -2.5 (-6.5 to 1.4) ms. There were significant differences between TVR latency and WBV-IMR latency in both the groups (mean (95% CI) difference; -6.2 (-9.3 to -3.0) ms, p = 0.0001 for the SCI group and -7.4 (-9.3 to -5.6) ms, p = 0.011 for Control group). CONCLUSIONS: The results suggest that the receptor of origin of TVR and WBV-IMR may be different.

Does the motor unit synchronization induced by vibration enhance maximal voluntary isometric contraction force? A randomized controlled double-blind trial.

OBJECTIVES: Motor unit synchronization has been proposed as a potential mechanism underlying muscle strength gains for vibration training, but it has yet to be definitely demonstrated. Aim of this study was to determine whether motor unit synchronization induced by vibration has an effect on isometric muscle strength. METHODS: Thirty-six healthy volunteers were randomized into two groups: the vibration and the control (sham vibration) groups. Two sets of test measurements and vibration resistance training between the two sets were applied to the right wrist flexors. The maximal voluntary isometric contraction force, and flexor carpi radialis EMG activity were recorded in the first (without vibratory stimulation) and the second (with vibratory stimulation) set. RESULTS: There was no difference in the normalized peak force between the first and the second set in the vibration group (p=0.554). Motor units fired with maximal voluntary isometric contraction synchronized at the vibration frequency (25 Hz) during vibration in all participants of the vibration group. CONCLUSION: The present study indicates that vibration-induced motor unit synchronization does not have a significant effect on the maximal voluntary isometric contraction force.​.

Vibration parameters affecting vibration-induced reflex muscle activity.

PURPOSE: To determine vibration parameters affecting the amplitude of the reflex activity of soleus muscle during low-amplitude whole-body vibration (WBV). MATERIALS AND METHODS: This study was conducted on 19 participants. Vibration frequencies of 25, 30, 35, 40, 45, and 50 Hz were used. Surface electromyography, collision force between vibration platform and participant's heel measured using a force sensor, and acceleration measured using an accelerometer fixed to the vibration platform were simultaneously recorded. RESULTS: The collision force was the main independent predictor of electromyographic amplitude. CONCLUSION: The essential parameter of vibration affecting the amplitude of the reflex muscle activity is the collision force.

Serum sclerostin is decreased following vitamin D treatment in young vitamin D-deficient female adults.

Sclerostin is produced almost exclusively by osteocytes, which also express receptors for 1,25 dihydroxyvitamin D3. The aim of this study was to investigate the effects of vitamin D3 treatment on serum sclerostin levels in young adult females with severe vitamin D deficiency. A total of 26 subjects were treated orally with calcium (1.200 mg/day for 2 months) and vitamin D3 (300.000 IU/week for 1 month). Serum 25-hydroxyvitamin D (25(OH)D) and sclerostin levels were measured before and after treatment. Baseline serum 25(OH)D and sclerostin levels were at 5.7 ± 2.4 ng/mL and 39.1 ± 14.4 pg/mL, respectively. Serum 25(OH)D was significantly increased, to 62.4 ± 18.7 ng/mL, following treatment; serum sclerostin was significantly decreased, to 29.3 ± 8.8 pg/mL. We conclude that serum sclerostin level is decreased following vitamin D3 treatment in patients with vitamin D deficiency.

The effect of single extremity-vibration on the serum sclerostin level.

[Purpose] Sclerostin is mechanosensitive protein that is produced exclusively by osteocytes. It was reported that the plasma sclerostin level increases in the 10th minute after the application of Whole-Body Vibration. The aim of this study was to determine whether single extremity-vibration induces any change in the serum sclerostin level. [Subjects and Methods] Eight healthy young-adult volunteers were recruited for this pilot study. The participants sat on a chair with their left hip and knee joints flexed at 90 degrees. The lower leg was exposed to vibration: 40 Hz, 4 mm, 60 s. Blood samples were collected before and after the vibration. The serum sclerostin levels were blindly measured in dual-controlled blood samples. [Results] The serum sclerostin level before vibration was 328.2±589.9 pg/ml, and it showed no significant change after vibration. [Conclusion] Unlike Whole-Body Vibration, Single-Extremity Vibration did not affect the serum sclerostin level significantly. This finding can be explained by the limited bone volume exposed to vibration. Bone volume exposed to vibration is less during Single-Extremity Vibration than during Whole-Body Vibration.

Whole-body vibration-induced muscular reflex: Is it a stretch-induced reflex?

[Purpose] Whole-body vibration (WBV) can induce reflex responses in muscles. A number of studies have reported that the physiological mechanisms underlying this type of reflex activity can be explained by reference to a stretch-induced reflex. Thus, the primary objective of this study was to test whether the WBV-induced muscular reflex (WBV-IMR) can be explained as a stretch-induced reflex. [Subjects and Methods] The present study assessed 20 healthy males using surface electrodes placed on their right soleus muscle. The latency of the tendon reflex (T-reflex) as a stretch-induced reflex was compared with the reflex latency of the WBV-IMR. In addition, simulations were performed at 25, 30, 35, 40, 45, and 50 Hz to determine the stretch frequency of the muscle during WBV. [Results] WBV-IMR latency (40.5 ± 0.8 ms; 95% confidence interval [CI]: 39.0-41.9 ms) was significantly longer than T-reflex latency (34.6 ± 0.5 ms; 95% CI: 33.6-35.5 ms) and the mean difference was 6.2 ms (95% CI of the difference: 4.7-7.7 ms). The simulations performed in the present study demonstrated that the frequency of the stretch signal would be twice the frequency of the vibration. [Conclusion] These findings do not support the notion that WBV-IMR can be explained by reference to a stretch-induced reflex.

Inhibitory kinesiotaping has no effect on post-stroke spasticity: Prospective, randomised, controlled study.

OBJECTIVE: Motor neuron pool activity is high in spasticity. The effect of inhibitory kinesiotaping (KT) on spasticity is unclear. The aim of this study is to investigate the effect of inhibitory KT on spasticity after stroke. METHODS: Fifty stroke patients with ankle plantarflexor spasticity were randomised to intervention (27) and control (23) groups. Inhibitory KT was applied to the triceps surae muscle in the intervention group and sham KT to the Achilles tendon in the control group. Inhibitory and sham KT were applied for 72 h with a combined conventional rehabilitation programme. Spasticity was assessed at baseline and 72 h after KT using three instruments: Modified Ashworth Scale (MAS), Homosynaptic Post-Activation Depression (HPAD) reflecting the level of motor neuron pool activity, and joint torque as a measure of resistance to passive ankle dorsiflexion. RESULTS: The baseline MAS score, HPAD levels and dorsiflexion torque of the two groups were not significantly different. The change in MAS score was -3.7 ± 17.5 (p = 0.180) in the intervention group and 3.6 ± 33.3 (p = 0.655) in the control group. The change in dorsiflexion torque was -0.3 ± 16.1 kg m (p = 0.539) in the intervention group and 8.0 ± 24.1 kg m (p = 0.167) in the control group. The change in mean HPAD was 8.7 ± 34.7 (p = 0.911) in the intervention group and 10.1 ± 41.6 (p = 0.609) in the control group. CONCLUSIONS: The present study showed that inhibitory KT has no antispastic effect in stroke patients.

Effects of sex steroids on serum sclerostin levels during the menstrual cycle.

BACKGROUND/AIMS: Previous studies on the effects of estrogen on sclerostin regulation were conducted in postmenopausal women in humans or animals following estrogen treatment or induced estrogen deficiency. The aim of this study was to evaluate the effects of sex hormones on serum sclerostin levels in premenopausal women with normal menstrual cycles. METHODS: A prospective observational clinical study. 80 voluntary premenopausal women were recruited for the study. Data from 31 patients were available for the statistical analysis. Serum sclerostin, free estradiol, free testosterone, and progesterone levels were measured during the menstruation, late follicular and mid-luteal phases. The unique protocol IDs were BEAH FTR-4 and NCT01418924 at ClinicalTrials.gov ID. RESULTS: Serum sclerostin values were 1.03 ± 0.58 ng/ml during the menstruation phase, 1.0 ± 0.36 ng/ml during the late follicular phase, and 1.18 ± 0.67 ng/ml during the mid-luteal phase (p = 0.543). There was no significant relationship between serum levels of sex steroids and sclerostin. CONCLUSIONS: Previous studies have not investigated the impact of sex hormone fluctuations on serum sclerostin levels during the menstrual cycle. The present study shows that serum sclerostin levels were not affected by sex steroids in premenopausal women with normal menstrual cycles.

A reliability study on the cumulative averaging method for estimating effective stimulus time in vibration studies.

Finding the reflex circuitry responsible for high-frequency vibration-induced muscle contraction takes work. The main challenge is to determine the effective stimulus time (EST) point at which continuous (sinusoidal) stimulation (i.e., vibration) triggers the reflex response. A novel "cumulated averaging method" has been previously proposed for estimating the EST point. In the current study, we aimed to test the reliability of the cumulated average method. We used five different whole-body vibration (WBV) frequencies in two experiments. The consistency between the EST points estimated from the first and second experiments was analysed with the intraclass correlation (ICC) and technical error of measurement (TEM). The ICC coefficient with 95% CI for the EST point estimation was 0.988 (0.950-0.997). The relative TEM was 1.3%. We concluded that the cumulated average method is highly reliable in estimating the effective stimulus time point for high-frequency continuous sinusoidal signals.

Estimating and minimizing movement artifacts in surface electromyogram.

While recording surface electromyography [sEMG], it is possible to record the electrical activities coming from the muscles and transients in the half-cell potential at the electrode-electrolyte interface due to micromovements of the electrode-skin interface. Separating the two sources of electrical activity usually fails due to the overlapping frequency characteristics of the signals. This paper aims to develop a method that detects movement artifacts and suggests a minimization technique. Towards that aim, we first estimated the frequency characteristics of movement artifacts under various static and dynamic experimental conditions. We found that the extent of the movement artifact depended on the nature of the movement and varied from person to person. Our study's highest movement artifact frequency for the stand position was 10 Hz, tiptoe 22, walk 32, run 23, jump from box 41, and jump up and down 40 Hz. Secondly, using a 40 Hz highpass filter, we cut out most of the frequencies belonging to the movement artifacts. Finally, we checked whether the latencies and amplitudes of reflex and direct muscle responses were still observed in the highpass-filtered sEMG. We showed that the 40 Hz highpass filter did not significantly alter reflex and direct muscle variables. Therefore, we recommend that researchers who use sEMG under similar conditions employ the recommended level of highpass filtering to reduce movement artifacts from their records. However, suppose different movement conditions are used. In that case, it is best to estimate the frequency characteristics of the movement artifact before applying any highpass filtering to minimize movement artifacts and their harmonics from sEMG.

Vitamin D levels in children with cerebral palsy.

PURPOSE: The aim of this study was to assess serum vitamin D levels and related factors in children with cerebral palsy (CP). METHODS: One hundred and nineteen children with CP between the ages of 1 year to 10 years 9 months who were admitted to the children's inpatient rehabilitation unit of a tertiary rehabilitation hospital between January 1, 2017, and December 31, 2018, were included in this study. Demographic and clinical characteristics were obtained from the patient files. CP types and serum 25 hydroxyvitamin D (25OHD) levels were recorded. Gross Motor Function Classification System (GMFCS) was used to assess the functional level. RESULTS: Mean age was 5.1±2.9 years. Forty-two (35.3%) were girls, 105 (88.3%) were spastic, and 14 (11.7%) were ataxic and mixed type CP. Mean GMFCS level was 4 (IQR:2). Thirty-one (26.1%) were getting extra liquid feed while the rest were eating a normal diet. Mean serum 25OHD level was 27.4±15.7 (3-79) ng/mL. Vitamin D levels were normal in 68 children (57.1%), whereas 36 (30.3%) had vitamin D insufficiency and 15 (12.6%) showed vitamin D deficiency. Those whose serum vitamin D levels were within a normal range had a median age of 3.8 (IQR:4.2) years. On the other hand, mean age was 6.4 (4.3) years for those with low vitamin D level (p < 0.0001). Vitamin D level was 19.8 (21.4) ng/mL in those (n = 88) who had regular diets, whereas it was 31.0 [16] ng/mL in those (n = 31) who were getting extra liquid feed (p = 0.015). There was no statistically significant correlation between vitamin D level and gender, GMFCS, CP type, season or antiepileptic drug treatment. A binary logistic regression model showed that older age and having only regular meals were significant risk factors for low vitamin D. CONCLUSION: In this study, 42.9% of the children with CP had low vitamin D. Older children with CP or those who had regular diets were higher risk groups in terms of low vitamin D.