Osteosarcopenia: where bone, muscle, and fat collide.

As the world's population ages, the prevalence of chronic diseases increases. Sarcopenia and osteoporosis are two conditions that are associated with aging, with similar risk factors that include genetics, endocrine function, and mechanical factors. Additionally, bone and muscle closely interact with each other not only anatomically, but also chemically and metabolically. Fat infiltration, a phenomenon observed in age-related bone and muscle loss, is highly prevalent and more severe in sarcopenic and osteoporotic subjects. Clinically, when individuals suffer a combination of both disorders, negative outcomes such as falls, fractures, loss of function, frailty, and mortality increase, thus generating significant personal and socio-economic costs. Therefore, it is suggested that when bone mineral density loss is synchronic with decreased muscle mass, strength, and function, it should be interpreted as a single diagnosis of osteosarcopenia, which may be preventable and treatable. Simple interventions such as resistance training, adequate protein and calcium dietary intake, associated with maintenance of appropriate levels of vitamin D, have a dual positive effect on bone and muscle, reducing falls, fractures, and, consequently, disability. It is essential that fracture prevention approaches-including postfracture management-involve assessment and treatment of both osteoporosis and sarcopenia. This is of particular importance as in older persons the combination of osteopenia/osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of institutionalization, falls, and fractures. This review summarizes osteosarcopenia epidemiology, pathophysiology, diagnosis, outcomes, and management strategies.

Functional imaging in obese children responding to long-term sports therapy.

Functional imaging studies on responders and non-responders to therapeutic interventions in obese children are rare. We applied fMRI before and after a one-year sports therapy in 14 obese or overweight children aged 7-16 years. During scanning, participants observed a set of standardized pictures from food categories, sports, and pleasant and neutral images. We were interested in alterations of the cerebral activation to food images in association with changes in the BMI-standard deviation score (BMI-SDS) after therapy and therefore separated the observation group into two outcome subgroups. One with reduction of BMI-SDS >0.2 (responder group) and one without (non-responder group). Before therapy fMRI-activation between groups did not differ. After therapy we found the following results: in response to food images, obese children of the responder group showed increased activation in the left putamen when compared with the non-responder group. Pleasant images evoked increased insula activation in the responder group. Only the responder group showed enhanced activity within areas known to store trained motor patterns in response to sports images. Both the putamen and the insula are involved in the processing of emotional valence and were only active for the therapy responders during the observation of food or pleasant stimuli. Elevated activity in these regions might possibly be seen in the context of an increase of dopaminergic response to emotional positive stimuli during intervention. In addition, sport images activated motor representations only in those subjects who profited from the sports therapy. Overall, an altered response to rewarding and pleasant images and an increased recruitment of motor engrams during observations of sports pictures indicates a more normal cerebral processing in response to these stimuli after successful sports therapy in obese children.

Increased dorsolateral prefrontal cortex activation in obese children during observation of food stimuli.

OBJECTIVE: Food cues yield different patterns of brain activation in obese compared with normal-weight adults in prefrontal and limbic/paralimbic areas. For children, no mapping studies comparing representation sites for food and other stimuli between obese and normal-weight subjects are available. DESIGN: We used a cross-sectional design of two age-matched subject groups to investigate differences in brain activation in response to visually presented food, pleasant, and neutral pictures between obese/overweight and normal children. SUBJECTS: 22 overweight/obese children were compared with 22 normal-weight children. MEASUREMENTS: Functional magnetic resonance imaging (of the whole head during perception of visually presented stimuli), psychological testing, and psychophysical measures of heart rate deceleration were assessed. RESULTS: Obese children showed higher activation of the dorsolateral prefrontal cortex (DLPFC) in response to food pictures. In addition, DLPFC activation was negatively correlated with self-esteem. In contrast, normal-weight children showed higher activation of the caudate and hippocampus specific to food pictures, and of the anterior cingulate cortex and thalamus to visual cues in general. In response to food stimuli, obese children showed a heart rate deceleration correlating positively with activation of the ventrolateral prefrontal cortex. CONCLUSION: Obese children react to food stimuli with increased prefrontal activation, which might be associated with increased inhibitory control.

Transfer from table to wheelchair in men and women with spinal cord injury: coordination of body movement and arm forces.

STUDY DESIGN: A complex set-up was used to investigate kinematics and ground reaction forces. SETTING: Motor Control and Physical Therapy Research Laboratory, Neurotec Department, Karolinska Institutet, Huddinge, Sweden. OBJECTIVE: To investigate how men and women with spinal cord injury (SCI) perform transfers from table to wheelchair with regard to timing and magnitude of force generation beneath the hands and associated body movements. METHODS: A total of 13 subjects (seven men, six women) with thoracic SCI. Kinematics of body movement were recorded (Elite 2000 system) simultaneously with the signals from three force plates (AMTI) placed beneath the buttocks and hands. Temporal and spatial parameters regarding head, trunk and trailing arm displacement, loading amplitudes and loading torque directions of both hands were analyzed for each trial and subject and compared between genders. RESULTS: Men and women used similar amplitudes of head bending and forward displacement of the trailing shoulder, while female subjects had significantly larger trunk rotation. Both genders applied significantly more weight on the trailing hand. Differences between genders were seen in direction and timing of peak torque beneath the hands. CONCLUSIONS: The forces beneath the trailing hand were larger than those in the leading, if there is weakness or pain in one arm, this arm should be selected as the leading. To avoid excessive load on the arms, technical aids and environmental factors should be very well adapted. SPONSORSHIP: This project was funded by the Swedish Research Council and the Health Care Science Committee of Karolinska Institutet.

Anticipatory postural adjustments in a bimanual, whole-body lifting task seem not only aimed at minimising anterior--posterior centre of mass displacements.

Anticipatory postural adjustments (APAs) were studied in a bimanual whole-body lifting task, using a mechanical analysis of the downward movement phase preceding loaded versus unloaded lifts. APAs in the backward ground reaction force were found to lead the perturbing forward box reaction with approximately 400 ms, thus inducing a backward centre of mass momentum. Both the APA onset and magnitude were scaled as a function of the load to be lifted. We conclude that, in this lifting task, the APAs served the generation of an appropriate extending moment of the ground reaction force after box pick-up, rather than the traditionally defined goal of minimising anterior-posterior centre of mass displacements.

Reaching-lifting-placing task during standing after stroke: Coordination among ground forces, ankle muscle activity, and hand movement.

OBJECTIVE: To investigate the coordination among hand movement, ground forces, and muscle activity in standing stroke patients reaching forward and lifting an object from a table. DESIGN: Survey. SETTING: Research laboratory. PATIENTS: Eight stroke patients and 8 persons serving as controls. MAIN OUTCOME MEASURE: Symmetry of percentage of body weight (BW) during initial standing, velocity and hand path trajectory, ankle muscle electromyography. Temporal and spatial parameters in percentage of movement time were recorded by using 2 forceplates, 3-dimensional kinematics, and surface electromyography. Motor function, sensory function, and functional performance were also assessed. RESULTS: Weight distribution during initial standing was significantly higher (57.4% +/- 8.1% BW) on the nonparetic leg. All subjects had preserved the preparatory loading phase, and after onset of hand movement loading shifted to the contralateral leg. Ankle muscle activity onset (lateral gastrocnemius [LG]) occurred after loading. In stroke subjects, LG was consistently activated first in the nonparetic leg, regardless of which arm performed the task. During paretic hand task, the reaching phase was significantly longer and the lifting phase significantly shorter compared with that of the nonparetic hand task and with that of the controls. In the paretic task, the hand path velocity was not bell-shaped; the object lifting was. CONCLUSIONS: Stroke subjects preserve the coordination between ground forces and hand movement. The lack of spontaneous use of the paretic hand is primarily caused by difficulties of planning the hand trajectory in space, as reflected by temporal and spatial parameters during task performance.

Coordinated ground forces exerted by buttocks and feet are adequately programmed for weight transfer during sit-to-stand.

The purpose of this study was to test the hypothesis whether weight transfer during sit-to-stand (STS) is the result of coordinated ground forces exerted by buttocks and feet before seat-off. Whole-body kinematics and three-dimensional ground forces from left and right buttock as well as from left and right foot were recorded for seven adults during STS. We defined a preparatory phase from onset of the first detectable anterior/posterior (A/P) force to seat-off (buttock forces fell to 0) and a rising phase from seat-off to the decrease of center of mass (CoM) vertical velocity to zero. STS was induced by an increase of vertical and backward directed ground forces exerted by the buttocks that significantly preceded the onset of any trunk movement. All ground forces peaked before or around the moment of seat-off, whereas all kinematic variables, except trunk forward rotation and hip flexion, peaked after seat-off, during or after the rising phase. The present study suggests that the weight transfer from sit to stand is induced by ground forces exerted by buttocks and feet before seat-off, i.e., during the preparatory phase. The buttocks generate the isometric "rising forces," e.g., the propulsive impulse for the forward acceleration of the body, while the feet apply adequate damping control before seat-off. This indicates that the rising movement is a result of these coordinated forces, targeted to match the subject's weight and support base distance between buttocks and feet. The single peaked, bell-shaped profiles peaking before seat-off, were seen beneath buttocks for the "rising drive," i.e., between the time of peak backward directed force and seat-off, as well as beneath the feet for the "damping drive," i.e., from onset to the peak of forward-directed force and for CoM A/P velocity. This suggests that both beginning and end of the weight transfer process are programmed before seat-off. The peak deceleration of A/P CoM took place shortly ( approximately 100 ms) after CoM peak velocity, resulting in a well controlled CoM deceleration before seat-off. In contrast to the view of other authors, this suggests that body equilibrium is controlled during weight transfer.

Forward leaning reaching task in sitting (FLRS): a new measure for clinical evaluation of hamstring length in children.

BACKGROUND AND PURPOSE: In this study, the rotation of the pelvis was taken into account when assessing the length of hamstrings. A new measure for clinical evaluation was developed to establish reference values of hamstring length in children without movement disabilities for different age groups. Subjects (N = 60) were 3-, 6-, 10- and 14-year-old children (N = 15 for each age group). These values could be helpful in deciding treatment interventions in children with movement disabilities, for example cerebral palsy, when hamstring length is in question. METHOD: The study was performed with subjects sitting and reaching for a touch control on a wall whilst voluntarily rotating the pelvis forwards. By use of digitized video frames, the spatial angles of the lumbar spine and pelvis, as well as the joint angles of hip and knee, were computed at the initial and end positions of a forward leaning reaching task in sitting (FLRS). The active forward leaning induced a forward rotation of the pelvis, causing stretch on the hamstring muscle with extended knee. RESULTS: The results of spatial and joint angle measurements suggest that the difference of the hip joint angle between initial erect and final forward leaned sitting may be used as reference values for hamstring length. Reference values are based on the mean (+/- SE) of means (mean of 15 children, that is, group and individual means of ten trials). CONCLUSIONS: The age group reference values obtained may indirectly give information as to whether the hamstring length of a child with cerebral palsy is within the normative value of age-related control subjects. The new test developed in this study provides a convenient means for measuring hamstring length and could enhance clinical evaluation.

Do infants have motor responses to sudden surface rotations in prone position?

This study investigated whether sudden rotation of the support surface (platform) triggers motor responses similar to reactions to sudden free fall in infants at very early age (2 to 5 weeks). Ten infants in prone position were exposed to sudden head-down rotation (mimicking the falling phase) and head-up rotation of the platform (mimicking landing phase) of 4 degrees or 6 degrees amplitude and 35 degrees/s velocity while EMGs and kinematics were recorded from the neck, trunk, and right arm. One infant, reassessed at 13 weeks, and one adult were tested for complementary developmental information. Sudden downward acceleration of the platform, induced either during head-down rotation or during the deceleration phase of head-up rotation, indeed mimicked falling and evoked in infants two-peaked EMG responses in the neck, trunk, and arm muscles, lasting in the latter over several hundred milliseconds. The activation pattern showed similarities to the adult and 13-week-old control subjects. The results suggested that the first burst may be ascribed to cutaneous pressure changes at the body and to vestibular signals triggering a startle-like response, whereas the second burst of the pattern in the arm is likely a candidate for an early substrate of the landing response normally seen during later stages of motor development. Head control appeared to be related more to its position with respect to the orientation of the trunk rather than to space in the infants and in the adult and might be due to the experimental paradigm, in which the surface accelerated away from the body and not, as during normal falling, when the body accelerates toward the support surface.

Myotatic reflex responses of non-disabled children and children with spastic cerebral palsy.

Surface electromyography (EMG) was used to examine lower-extremity myotatic reflex responses following patellar or Achilles tendon taps to normally developing, non-disabled infants and to individuals with cerebral palsy (CP). Reflex irradiation was present in non-disabled infants and infants with CP under two years of age. The only significant differences in myotatic reflex responses between the two groups at this age was the higher amplitude of the directly stimulated muscle of children with CP. After two years the amplitude did not differ between groups. Reflex irradiation, however, was greatly reduced in the non-disabled children but not in the children with cerebral palsy. These findings and those of non-human animal studies indicate the possible neural mechanisms that underlie reflex irradiation of individuals with CP. The potential clinical relevance of these findings is discussed.

Analysis of the New Zealand Black contribution to lupus-like renal disease. Multiple genes that operate in a threshold manner.

F1 progeny of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune process remarkably similar to human systemic lupus erythematosus. Previous studies have implicated major genetic contributions from the NZW MHC and from a dominant NZB gene on chromosome 4. To identify additional NZB contributions to lupus-like disease, (NZB x SM/J)F1 x NZW backcross mice were followed for the development of severe renal disease and were comprehensively genotyped. Despite a 50% incidence of disease, significant associations between the presence of the NZB genotype and disease were noted on chromosomes 1, 4, 7, 10, 13, and 19. The data indicated that multiple NZB genes, in different combinations, contribute to severe renal disease, and that no single gene is required. To further investigate this NZB contribution, NZB x SM/J (NXSM) recombinant inbred (RI) strains were crossed with NZW mice, and F1 progeny were analyzed for the presence of lupus-like renal disease. Interestingly, nearly all of the (RI x NZW)F1 cohorts studied expressed some level of disease. Five RI strains generated a high incidence of disease, similar to (NZB x NZW)F1 mice, and nearly one-half of the cohorts developed disease at intermediate levels. Only two cohorts demonstrated very little disease, supporting the conclusion that multiple genes are capable of disease induction. Experiments correlating the genotypes of these RI strains with their ability to generate disease revealed that none of the disease-associated loci defined by the backcross analysis were present in all five RI strains that generated disease at high levels. Overall, both the backcross data and RI analysis provide additional support for the genetic complexity of lupus nephritis and uphold the conclusion that heterogeneous combinations of contributing NZB genes seem to operate in a threshold manner to generate the disease phenotype.

Postural adjustments in sitting humans following external perturbations: muscle activity and kinematics.

There are several controversies concerning the organization and induction of postural adjustments in standing humans. Some investigators suggest the responses are triggered by somatosensory inputs (especially from the ankle in standing subjects), while others emphasize the vestibular input induced by head acceleration. We examined postural responses in sitting subjects in order to describe the muscle activation pattern during various perturbations and to test whether somatosensory or vestibular stimulation elicited the responses. The kinematics and EMG patterns in response to perturbations caused by movements of the support surface were studied in adults. The postural muscle activation following a backward sway was mainly the same, whether it was elicited by a forward translation or a legs-up rotation. This is remarkable, since, except for pelvis rotation, the movements of all body segments including the head differed in the two conditions. Furthermore, a second experiment showed that the direction of the initial head movement could be reversed with retainment of the same postural muscle activation pattern. The results suggest that somatosensory signals derived from the backward rotation of the pelvis, and not vestibular information from the head, trigger postural responses during sitting. There was a slight but consistent difference in the muscle activation pattern, whether the backward sway was elicited by a forward translation or legs-up rotation. The difference seemed to reflect the sensory information from head and other body parts (except the pelvis). This finding allowed us to speculate in a central pattern generator for postural adjustments containing two levels. At the first level, a simple format of the muscle activation would be generated; at the second level, the centrally generated pattern could be shaped and timed by interaction from the entire somatosensory, vestibular, and visual input.

Epigenetic development of postural responses for sitting during infancy.

This study examined whether postural responses emerge in children in a predetermined way before independent sitting is achieved, and in what respect postural responses in infants differ from those in adults. Children just able to sit independently and children not yet able to sit were exposed to surface perturbations (translation and rotation) while body movement and electromyographic (EMG) responses were recorded. Perturbations causing a backward sway of the body (i.e., forward translation and legs-up rotation), elicited consistent patterns of muscle activity in ventral hip, trunk, and neck muscles in the independently sitting children. A high tonic EMG background activity in trunk and neck extensor muscles was inhibited at the onset of the ventral muscle activity. Kinematic analysis revealed that backward rotation of the pelvis was the first detectable body movement, while head movements (linear and angular displacement) were irregular and occurred later than the pelvis movement. Perturbations in the opposite direction, causing a forward sway, evoked variable responses in dorsal trunk and neck muscles, suggesting that the excitability level for postural responses was set according to the stability limits of the body. Children not yet able to sit without support were tested when the support around the waist, given by the experimenter's hands, was released prior to the onset of the platform perturbation. Postural responses were elicited in ventral muscles following a backward sway in all children and in about 60% of all trials. Often, only some of the ventral muscles were activated. No distinct responses were evoked during perturbations imposing a forward sway. These results suggest that (1) backward rotation of the pelvis triggers the postural adjustments in the independently sitting children; (2) a basic form of the postural adjustment develops in a predetermined manner before children practice independent sitting; and (3) the basic structure of ventral muscle activation pattern resembles that of adults, while the activation of the dorsal muscles (inhibition) differs in several aspects. These findings are in agreement with a recent model of central pattern generators for postural responses consisting of two operative levels. At the first level, which is triggered by backward rotation of the pelvis, the basic activation pattern is generated. At the second level, the pattern is shaped and fine-tuned by multisensory interactions from all activated sensory systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Development of anticipatory postural adjustments during locomotion in children.

1. Anticipatory postural adjustments were studied in children (6-14 yr of age) walking on a treadmill while pulling a handle. Electromyographs (EMGs) and movements were recorded from the left arm and leg. 2. Postural activity in the leg muscles preceded voluntary arm muscle activity in all age groups, including the youngest children (6 yr of age). The latency to both leg and arm muscle activity, from a triggering audio signal, decreased with age. 3. In older children the latency to both voluntary and postural activity was influenced by the phase of the step cycle. The shortest latency to the first activated postural muscle occurred during single support phase in combination with a long latency to arm muscle activity. 4. In the youngest children, there was no phase-dependent modulation of the latency to the activation of the postural muscles. The voluntary activity was delayed during the beginning of the support phase resulting in a long delay between leg and arm muscle activity. 5. The postural muscle activation pattern was modified in a phase-dependent manner in all children. Lateral gastrocnemius (LG) and hamstring muscles (HAM) were activated during the early support phase, whereas tibialis anterior (TA) and quadriceps (Q) muscles were activated during the late support phase and during the swing phase. However, in the 6-yr-old children, LG was also activated in the swing phase. LG was activated before the HAM activity in the youngest children but after HAM in 14-yr-old children and adults. 6. The occurrence of LG activity in postural responses before heel strike suggests an immature (nonplantigrade) gating of postural activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase-dependent modulations of anticipatory postural activity during human locomotion.

1. The ability of the CNS to coordinate several motor tasks was studied in humans walking on a treadmill while pulling on a handle. Subjects were instructed to respond to an audio signal that was presented in different phases of the step cycle. Electromyograph (EMG) and movements were recorded from the left arm and leg. 2. The activity of the arm muscle was preceded by postural activity in the leg muscles. The pattern of the anticipatory postural activity differed in the various phases of the step cycle. Lateral gastrocnemius and hamstring muscles were activated during responses occurring in the early support phase whereas tibialis anterior and quadriceps muscles were activated when the pull was exerted during the late support phase and during the swing phase. In the middle of the support phase the combination of both muscle activity was present. 3. The temporal sequencing and the spatial distribution of the anticipatory muscle activity changed gradually. Early during the support phase the hamstring muscles were activated before the gastrocnemius muscle, whereas the order was reversed during midstance. The EMG amplitude of the hamstring and gastrocnemius muscles was largest in the beginning of the support phase and then gradually decreased, whereas the amplitude of the tibialis anterior and quadriceps muscles increased during the later parts of the support phase. 4. The anticipatory responses to pulls exerted during the first part of the support phase reduced the ankle flexion during the single support phase.(ABSTRACT TRUNCATED AT 250 WORDS)

The development of independent walking in children with cerebral palsy.

Electromyographic and kinematic data were collected during treadmill locomotion by normal infants and infants with cerebral palsy. Locomotor patterns of the infants with cerebral palsy were similar to those of normal infants during the stage of supported locomotion, but as they matured, some of the characteristics of the infant stepping pattern, such as synchronous muscle activity with excessive muscular co-contraction and short-latency reflexes at foot contact, were retained. The normal plantigrade features of adult gait did not develop in these children.

Myotatic reflex development in normal children and children with cerebral palsy.

Neonatal neuronal exuberance and its retention following neonatal brain damage have been demonstrated in a number of species but not in humans. The purpose of the present ongoing study is to determine if there is any evidence of neonatal neuronal exuberance and its retention following damage to the CNS in the human. Of equal concern is the determination of the neurological mechanisms underlying abnormal movement and reflex development in children with cerebral palsy.

Deficits in reciprocal inhibition of children with cerebral palsy as revealed by H reflex testing.

Experiments were performed to determine whether spinal and supraspinal components of reciprocal inhibition (a neural mechanism responsible for the prevention of muscular co-ordination during voluntary movement) were present in groups of non-disabled children and children with cerebral palsy. Changes in the gastrocnemius-soleus H reflex were examined during voluntary dorsiflexion and plantarflexion of the ankle and during a vibration applied to the anterior tibial tendon. The results indicate that children with cerebral palsy have impairments in reciprocal inhibition, both before and during voluntary movement. These deficits, which involve damage to supraspinal centres, contribute to their inability to perform smooth, co-ordinated movements.