Showing papers in "Journal of Musculoskeletal & Neuronal Interactions in 2010"

Reporting whole-body vibration intervention studies: recommendations of the International Society of Musculoskeletal and Neuronal Interactions.

Abstract: Whole-body vibration (WBV) is receiving increasing interest as a therapeutic modality to improve neuromuscular performance or to increase bone mass or density In order to help improve the quality of reports about WBV treatment studies, the International Society of Musculoskeletal and Neuronal Interactions (ISMNI) invited experts in the field to provide suggestions on how the intervention should be described in such reports The recommendations are presented here

The development and morphogenesis of the tendon-to-bone insertion - what development can teach us about healing -.

Abstract: The attachment of dissimilar materials is a major challenge because of the high levels of stress that develop at such interfaces. An effective solution to this problem develops at the attachment of tendon (a compliant “soft tissue”) to bone (a stiff “hard tissue”). This tissue, the “enthesis”, transitions from tendon to bone through gradations in structure, composition, and mechanical properties. These gradations are not regenerated during tendon-to-bone healing, leading to a high incidence of failure after surgical repair. Understanding the development of the enthesis may allow scientists to develop treatments that regenerate the natural tendon-to-bone insertion. Recent work has demonstrated that both biologic and mechanical factors drive the development and morphogenesis of the enthesis. A cascade of biologic signals similar to those seen in the growth plate promotes mineralization of cartilage on the bony end of the enthesis and the formation of fibrocartilage on the tendon end of the enthesis. Mechanical loading is also necessary for the development of the enthesis. Removal of muscle load impairs the formation of bone, fibrocartilage, and tendon at the developing enthesis. This paper reviews recent work on the development of the enthesis, with an emphasis on the roles of biologic and mechanical factors.

Myostatin (GDF-8) as a key factor linking muscle mass and bone structure.

Abstract: Myostatin (GDF-8) is a member of the transforming growth factor-beta (TGF-β) superfamily that is highly expressed in skeletal muscle, and myostatin loss-of-function leads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a model for studying muscle-bone interactions, and here we review the skeletal phenotype associated with altered myostatin signaling. It is now known that myostatin is a key regulator of mesenchymal stem cell proliferation and differentiation, and mice lacking the myostatin gene show decreased body fat and a generalized increase in bone density and strength. The increase in bone density is observed in most anatomical regions, including the limbs, spine, and jaw, and myostatin inhibitors have been observed to significantly increase bone formation. Myostatin is also expressed in the early phases of fracture healing, and myostatin deficiency leads to increased fracture callus size and strength. Together, these data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells, and that myostatin antagonists and inhibitors are likely to enhance both muscle mass and bone strength.

Role of muscle-derived growth factors in bone formation.

Abstract: Muscle and bone anabolism and catabolism are tightly coupled during growth, development, and aging, yet the cellular and molecular mechanisms linking these two tissues are not well understood. Here we show that FGF-2 and IGF-1, two growth factors known to play a major role in regulating bone formation, are localized to muscle fibers along the muscle-bone interface of the mouse forelimb. Likewise, receptors for these growth factors are also abundant in periosteum adjacent to fleshy muscle attachments along the diaphysis of long bones. Growth factor levels were quantified from homogenized mouse forelimb muscles and IGF-1 was found to be the most abundant factor with FGF-2 also detected. Growth factor levels were also analyzed in conditioned medium from cultured myotubes, and IGF-1 and FGF-2 were again detected at significant levels. Mechanically wounding C2C12 myotubes increased the release of FGF-2 into conditioned medium, whereas IGF-1 was secreted at lower concentrations than FGF-2 following injury. Together these findings suggest that muscle is an important, local source of growth factors for bone tissue. Hence, the integrated growth and development of bone and muscle is likely to be regulated in part by paracrine mechanisms at the muscle-bone interface involving growth factor signaling.

Is bone formation induced by high-frequency mechanical signals modulated by muscle activity?

Abstract: Bone formation and resorption are sensitive to both external loads arising from gravitational loading as well to internal loads generated by muscular activity. The question as to which of the two sources provides the dominant stimulus for bone homeostasis and new bone accretion is arguably tied to the specific type of activity and anatomical site but it is often assumed that, because of their purportedly greater magnitude, muscle loads modulate changes in bone morphology. High-frequency mechanical signals may provide benefits at low- ( 1g) acceleration magnitudes. While the mechanisms by which cells perceive high-frequency signals are largely unknown, higher magnitude vibrations can cause large muscle loads and may therefore be sensed by pathways similar to those associated with exercise. Here, we review experimental data to examine whether vibrations applied at very low magnitudes may be sensed directly by transmittance of the signal through the skeleton or whether muscle activity modulates, and perhaps amplifies, the externally applied mechanical stimulus. Current data indicate that the anabolic and anti-catabolic effects of whole body vibrations on the skeleton are unlikely to require muscular activity to become effective. Even high-frequency signals that induce bone matrix deformations of far less than five microstrain can promote bone formation in the absence of muscular activity. This independence of cells on large strains suggests that mechanical interventions can be designed that are both safe and effective.

Vibration treatment in cerebral palsy: A randomized controlled pilot study.

Abstract: In this 6-month trial, twenty children with cerebral palsy (age 6.2 to 12.3 years; 6 girls) were randomized to either continue their school physiotherapy program unchanged or to receive 9 minutes of side-alternating whole-body vibration (WBV; Vibraflex Home Edition II, Orthometrix Inc) per school day in addition to their school physiotherapy program. Patients who had received vibration therapy increased the average walking speed in the 10 m walk test by a median of 0.18 ms(-1) (from a baseline of 0.47 ms(-1)), whereas there was no change in the control group (P=0.03 for the group difference in walking speed change). No significant group differences were detected for changes in areal bone mineral density (aBMD) at the lumbar spine, but at the distal femoral diaphysis aBMD increased in controls and decreased in the WBV group (P=0.03 for the group difference in aBMD change). About 1% of the WBV treatment sessions were interrupted because the child complained of fatigue or pain. In conclusion, the WBV protocol used in this study appears to be safe in children with cerebral palsy and may improve mobility function but we did not detect a positive treatment effect on bone.

Fall predictors in the community dwelling elderly: a cross sectional and prospective cohort study.

Abstract: Objectives: To ascertain the risk factors for falls, stumbles and recurrent falls in a cohort of elderly people with mean age of 76.7-/+6.1 years. Methods: 137 community dwelling elderly living independently or in assisted living institutions participated in the study. Each subject was assessed by history, physical examination and physical performance tests at the beginning and end of study. Falls and stumbles were recorded in a falls dairy for 1 year. Results: Significant predictors of being a faller were a history of falls at baseline (Odds Ratio (OR) = 3.85, 95% Confidence Interval (CI) = 1.56 - 9.50), depression (OR = 1.19, 95% CI = 1.02 - 1.38) and timed rise (Incident Rate Ratio (IRR) = 1.24, 95% CI = 1.03 - 1.50). For predicting recurrent fallers Receiver Operator Characteristic (ROC) curves were as follows: 0.71 (95%CI 0.61-0.81) for timed up and go, 0.67 (95%CI 0.56-0.78) for timed rise and 0.70 (95%CI 0.60-0.80) for timed walk fast pace. Conclusions: Timed rise was the single most important test that was able to predict both a first time faller and recurrent faller. Timed up and go was the most significant test to predict recurrent fallers. Language: en

Reproducibility of jumping mechanography in healthy children and adults.

Abstract: Objectives: To describe mechanographic tests that can be performed by patients with a range of functional abilities and to assess the reproducibility of test results in healthy adults and children. Methods: Fifteen adults and 13 children underwent two separate sessions, one week apart. Participants performed five different tests in both sessions: Multiple one-legged hopping, multiple two-legged hopping, single two-legged jump, heel-rise test, chair-rise test. All measurements were recorded with a portable force platform. Results: The main outcome measures of each test (peak force relative to body weight or peak power relative to body weight, depending on the test) showed no systematic differences between Session 1 and 2 for any of the test results. Coefficients of variation for the suggested main outcome parameters ranged between 3.4% and 7.5% for multiple one-legged hopping, multiple two-legged hopping, single two-legged jump and the heel-rise test, but were higher for the chair-rise test (8.0% in adults, 15.6% in children). Conclusions: The five mechanographic tests assessed in the present study yield reproducible outcome measures in healthy subjects. It is justified to evaluate the usefulness of these tests in different patient populations.

The biomechanical effects of focused muscle training on medial knee loads in OA of the knee: a pilot, proof of concept study.

Abstract: Background: High dynamic loads of the medial knee are associated with tibiofemoral osteoarthritis (OA) severity and progression. The lower extremity acts as an integrated kinetic unit, thus treatments targeting adjacent segments may promote reductions in the loading of a symptomatic knee. This study examined the biomechanical effects of a lower extremity exercise regimen, emphasizing training of hip abductor musculature, on dynamic knee loads in individuals with knee OA. Methods: Six subjects with medial compartment knee OA participated in a proof of concept study of a four-week exercise program specifically targeting the hip abductor musculature in combination with traditional quadriceps and hamstring training. Assessments included gait analyses to measure the external knee adduction moment, a surrogate marker of medial knee joint loading as well as WOMAC questionnaires and strength evaluations. Results: All subjects demonstrated a decrease in their external knee adduction moment, with an average decrease of 9% (p<0.05) following the exercise intervention. There was a 78% (p<0.05) decrease in WOMAC knee pain scores. Conclusions: These results suggest that targeting hip, rather than only knee musculature, may represent an effective biomechanically-based treatment option for medial knee OA.

Effect of a new physiotherapy concept on bone mineral density, muscle force and gross motor function in children with bilateral cerebral palsy.

Abstract: Objective: The purpose of this study was to determine the effect of a new physiotherapy concept on bone density, muscle force and motor function in bilateral spastic cerebral palsy children. Methods: In a retrospective data analysis 78 children were analysed. The concept included whole body vibration, physiotherapy, resistance training and treadmill training. The concept is structured in two in-patient stays and two periods of three months home-based vibration training. Outcome measures were dual-energy x-ray absorption (DXA), Leonardo Tilt Table and a modified Gross Motor Function Measure before and after six months of training. Results: Percent changes were highly significant for bone mineral density, -content, muscle mass and significant for angle of verticalisation, muscle force and modified Gross Motor Function Measure after six months training. Conclusions: The new physiotherapy concept had a significant effect on bone mineral density, muscle force and gross motor function in bilateral spastic cerebral palsy children. This implicates an amelioration in all International Classification of Functioning, Disability and Health levels. The study serves as a basis for future research on evidence based paediatric physiotherapy taking into account developmental implications.

The potential role of muscle in bone repair.

Abstract: Bone repair is a complex phenomenon involving many cell types and signaling factors. Substantial evidence exists to suggest that stem cells originating from local osseous tissues, particularly the periosteum, can contribute to bone repair. However, there are situations where injury or post-surgical management can deplete the amount of, and/or access to these crucial progenitors. The fact that bone repair can still occur in these circumstances implicitly reflects the existence of compensatory secondary systems. One potential alternate source of osteoprogenitors is muscle, which is closely associated with bone and typically suffers trauma during an orthopedic insult. While muscle access is known to be beneficial to bone repair, this is conventionally credited to its high vascularity, and thus its contribution to the local blood supply. However, there is emerging evidence to suggest that progenitors from muscle may directly contribute to bone healing. Defining the role of muscle in bone formation and repair has significant clinical implications, particularly where promoting access to this tissue may enhance the repair outcome.

Biological underpinnings of Frost's mechanostat thresholds: the important role of osteocytes.

Abstract: Harold Frost first proposed the existence of several mechanical thresholds in bone, two of which determine whether bone is added to, or lost from, the skeleton. Recent evidence from bone biology helps elucidate the role of osteocytes in determining these mechanical thresholds. Specifically, when mechanical stimuli fall below the resorption threshold, osteocyte apoptosis occurs, followed by bone resorption. Conversely, mechanical loading maintains osteocytes viability, and consequently, no bone is lost. With a greater than customary mechanical stimulus, osteocytes perturbation from pulsatile fluid flow results in release of anabolic factors and subsequent bone formation. Osteocytes also play a pivotal role in bone remodeling in response to alterations in the mechanical environment. In particular, osteocyte apoptosis results in bone turnover in disuse as well as in response to greater than customary mechanical stimuli due to microdamage accumulation. Given the important role of osteocytes in bone modeling and remodeling, these cells provide an ideal target for both drug therapies and exercise to prevent bone fragility.

Dynamic skeletal muscle stimulation and its potential in bone adaptation

Abstract: To identify mechanotransductive signals for combating musculoskeletal deterioration, it is essential to determine the components and mechanisms critical to the anabolic processes of musculoskeletal tissues. It is hypothesized that the interaction between bone and muscle may depend on fluid exchange in these tissues by mechanical loading. It has been shown that intramedullary pressure (ImP) and low-level bone strain induced by muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia. Optimized MS signals, i.e., low-intensity and high frequency, may be critical in maintaining bone mass and mitigating muscle atrophy. The objectives for this review are to discuss the potential for MS to induce ImP and strains on bone, to regulate bone adaptation, and to identify optimized stimulation frequency in the loading regimen. The potential for MS to regulate blood and fluid flow will also be discussed. The results suggest that oscillatory MS regulates fluid dynamics with minimal mechanical strain in bone. The response was shown to be dependent on loading frequency, serving as a critical mediator in mitigating bone loss. A specific regimen of dynamic MS may be optimized in vivo to attenuate disuse osteopenia and serve as a biomechanical intervention in the clinical setting.

The effect of muscle dysfunction on bone mass and morphology

Abstract: There is little doubt that skeletal development and subsequent maintenance of bone mass and morphology during adulthood is greatly influenced by viable muscle function. In this review, we will summarize human observations that support this concept, then focus on models that have enabled (or may enable in the future) insight into the co-dependency of muscle and bone. Specifically, we will summarize data generated with three types of models: 1) spinal cord injury models, 2) transgenic mice with altered muscle function, and 3) experimental models affecting one hindlimb or a single muscle group. In sum, these data clearly support the concept that muscle function is critical for the successful development of the skeleton and is likely to play an important role in mediating bone health through life. The specific signaling pathways by which this interdependency is achieved, however, remain to be clarified.

The 2nd Berlin BedRest Study: protocol and implementation

Abstract: Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed.

Role of neuropathy on fracture healing in Charcot neuro-osteoarthropathy.

Abstract: Charcot neuro-osteoarthropathy (CNO) is a devastating condition affecting most commonly the foot/ankle joint in diabetic patients and may lead to severe deformities and amputation. Peripheral sensory neuropathy seems to be a pre-requisite to the development of CNO. The aim of this review article is to summarise the skeletal effects of the nervous system on bone remodelling and fracture healing of normal and damaged joints and to describe how neuropathy, in the context of modern concept of neuro-osteopathology, is crucial in the predisposition of the patient to develop acute CNO.

Muscle cross sectional area and grip torque contraction types are similarly related to pQCT derived bone strength indices in the radii of older healthy adults.

Abstract: OBJECTIVES We sought to identify the variance in radius bone strength indices explained by forearm muscle cross sectional area (MCSA) and isometric (ISO), concentric (CON), or eccentric (ECC) grip torque in healthy men and postmenopausal women when gender and body size were controlled for. Additionally we assessed variance in various grip contractions explained by MCSA. METHODS pQCT estimated bone strength of the radius and forearm MCSA were measured from 45 healthy adults (59.4-/+7.2 yrs). Isokinetic dynamometry was used to assess peak grip torque. Regressions were adjusted for gender and radius length. RESULTS Peak grip torques were not independent predictors (p>0.05) of distal radius bone strength in compression (bone strength index; BSI(c)) when gender was included in the prediction model. Gender was not a contributor to any model that included MCSA (p>0.05). At the diaphysis all torque measures, MCSA, gender, and length, significantly contributed to predict similar portions (79-80%) of the stress strain index (SSI(p); strength in torsion). MCSA accounted for 68-76% of variance in grip torque (p<0.05). CONCLUSIONS When estimating radius bone strength, forearm MCSA is a comparable predictor to CON, ISO, and ECC grip torques and is also a good surrogate of these contraction types.

Masticatory biomechanics and masseter fiber-type plasticity.

Abstract: Compared to force-resisting elements of the mammalian feeding apparatus, data on jaw-muscle plasticity are less common. This hinders our understanding of the role of force-producing structures in craniofacial development and integration. Thus, we investigated fiber-type abundance and cross-sectional area in the masseter muscle of growing rabbits subjected to diet-induced variation in masticatory stresses. Three loading cohorts were obtained as weanlings and raised until adult on different diets. Immediately following euthanasia, left-sided masseters were dissected away, weighed, and then divided into anterior, intermediate and posterior sections for fiber-type immunohistochemistry. These data were compared to mandibular proportions and biomineralization from the same subjects. Results indicate that growing mammals fed a tougher, fracture-resistant diet develop: absolutely and relatively lower numbers of Type I jaw-muscle fibers; absolutely larger fiber cross-sectional areas; and relative increases in the amount of Type II fibers. These analyses indicate that an early postweaning dietary shift can induce significant variation in muscle fiber types. Such norms of reaction are comparable to those observed in bony elements. Functionally, the processing of fracture-resistant foods results in jaw adductors potentially characterized by faster contraction times and higher force production capabilities, which may influence the frequency and amplitude of forces experienced by oral tissues.

Relationships between calf muscle density and muscle strength, mobility and bone status in the stroke survivors with subacute and chronic lower limb hemiparesis.

Abstract: Objective: To determine the relationship between muscle density and neuromusculoskeletal status in stroke survivors with subacute and chronic hemiparesis. Methods: Community-dwelling adults were recruited into one of 3 groups (11 per group): subacute stroke group (SSG, 1 year post-stroke), or age- and gender-matched control group (CG). Muscle density, muscle mass and tibial bone status (cortical density, mass and polar stress-strain index (pSSI)) were measured bilaterally at the tibial 66% site using peripheral quantitative computed tomography. Muscle strength of ankle plantarflexors and knee extensors was assessed using isokinetic dynamometry. Mobility was assessed using the Berg Balance Scale. Univariate regression analyses by group tested whether side-to-side differences in muscle density and measures of neuromusculoskeletal status were related. Results: In the SSG and CG, relationships were observed for muscle density and ankle plantarflexor strength (R 2 = 0.365 and 0.503). Muscle density related to muscle mass in the CG only (R 2 = 0.889). Muscle density related to cortical bone density in the SSG (R 2 = 0.602) and pSSI in the CSG (R 2 = 0.434). Conclusions: Muscle density may provide insight into the side-to-side changes in muscle and bone strength following hemiparetic stroke.

Prevention of heterotopic ossification in cases of hypertrophic osteoarthritis submitted to total hip arthroplasty. Etidronate or Indomethacin

Abstract: We present a study comparing etidronate or indomethacin for the prevention of heterotopic ossification after total hip arthroplasty in patients with hypertrophic osteoarthritis. 52 patients were divided in two groups. Group A (26 patients) received etidronate (20 mg/kg/day for 12 weeks) and Group B (26 patients) indomethacin 75 mg/day for 2 weeks. Mean follow up was 36 months (range, 18 to 50 months). The incidence of side effects was 15.4% in group A and 30.8% in group B (p=0.324). At 6 months there was no statistically significant difference in terms of clinical (p=0.532) and radiographic evaluation between the two groups (p=0.303). However, the cost of etidronate which may be as much as six times more expensive than that of indomethacin could not justify its routine prophylactic use.

A thermodynamic model of bone remodelling: the influence of dynamic loading together with biochemical control.

Abstract: Understanding of the bone remodelling process has considerably increased during the last 20 years. Since the ability to simulate (and predict) the effects of bone remodelling offers substantial insights, several models have been proposed to describe this phenomenon. The strength of the presented model is that it includes biochemical control factors (e.g., the necessity of cell-to-cell contact, which is mediated by the RANKL-RANK-OPG chain during osteoclastogenesis) and mechanical stimulation, the governing equations are derived from interaction kinetics (e.g., mass is preserved in running reactions), and the parameters are measurable. Behaviour of the model is in accordance with experimental and clinical observations, such as the role of dynamic loading, the inhibitory effect of dynamic loading on osteoclastogenesis, the observation that polykaryon osteoclasts are activated and formed by a direct cell-to-cell contact, and the correct concentrations of osteoblasts, osteoclasts, and osteocytes. The model does not yet describe the bone remodelling process in complete detail, but the implemented simplifications describe the key features and further details of control mechanisms may be added.

Skeletal phenotype of mice with a null mutation in Cav 1.3 L-type calcium channel

Abstract: This study aimed to understand the role of Cav1.3, one of the four L-type voltage sensitive calcium channels (VSCC) alpha(1) subunits, in the skeletal response to mechanical loading and intermittent PTH treatment. The Cav1.3 mRNA is expressed in osteoblasts. The Cav1.3 mRNA level in male wild type mice is higher than those in female. Loss of Cav1.3 resulted in a smaller skeleton in male mice as indicated by significantly lower body weight, less bone mineral content and smaller cross-sectional area of femoral midshaft. However, the osteogenic response to mechanical loading of the ulna was normal in Cav1.3(-/-) compared to the normal control mice. Male mice Cav1.3(-/-) were then treated daily with PTH at a dose of 40 microg/kg. A 6-week course of intermittent PTH treatment enhanced bone mineral content and mechanical strength equally in wild type control and Cav1.3 null mice. We also found that Cav1.2 subunit significantly increases in the absence of Cav1.3 gene. In conclusion, Cav1.3 is involved in bone metabolism, especially in male mice. Cav1.3 does not mediate osteoblast response to mechanical loading and PTH. Our data suggest that Cav1.1 and Cav1.2 subunits may substitute for Cav1.3 to maintain bone response to mechanical loading.

Structural changes in the ageing periosteum using collagen III immuno-staining and chromium labelling as indicators.

Abstract: The periosteum and Sharpey's fibre extensions occupy the musculoskeletal interface and may be strategic in age-related deterioration. Because of its exceptionally powerful insertions the porcine mandible is an ideal model and its periosteal system was compared in 4 separate regions of adult young (1 year) and older (3 year) animals. These were examined by undecalcified histology, collagen immunohistochemistry and mineral histochemistry using polarization, epifluorescence and laser confocal microscopy; mineral ultrastructure was facilitated by chromium labelling with EDX microanalysis. Birefringent Sharpey's fibres were coarse (>8 microm) or fine and classified as horizontal (more common with age), oblique (most common in youth) or vertical (least common); in addition they were designated "superficial", "transcortical" and "intertrabecular" (the latter being deep, coarse and vertical). Their specific affinity for collagen type III FITC-labelled antibody demonstrated 3-dimensional arrays of bone-permeating fibres. With age at each region the cortical thickness rose (e.g. 4.9 mm to 9.3 mm), the periosteum thinned (e.g. 180-/+7 microm to 129-/+8 microm; p<0.001), and the periosteum: bone ratio diminished (e.g. 3.65-/+0.36 to 1.40-/+0.14; p<0.001) while Sharpey's fibres became fewer, fragmented, superficial and shortened (e.g. 226-/+27 microm to 55-/+6 microm; p<0.001). Accompanying was the sporadic encroachment of calcified particles, 1 microm diameter, in irregular periosteal aggregates or interlinked around Sharpey bundles (resembling calcifying turkey leg tendon). EDX microanalysis confirmed prominent chromium spectral peaks in the older periosteum only, coincident with chromium-labelled mineral "ghosts". It was concluded that the periosteum and Sharpey's fibres, deep-penetrating and complex in youth, partially hardens and regresses with age with implications for its functional properties.

Osteoprotegerin and nuclear factor-kappaB ligand are associated with leptin and adiponectin levels, in apparently healthy women.

Abstract: Objectives: We investigated the relationship between the major bone turnover markers, i.e., Osteoprotegerin (OPG) and Receptor activator of nuclear factor-kappaB ligand (RANKL) and serum adipokines (leptin, adiponectin) levels in a sample of apparently healthy women. Methods: A random sample which consisted of 80 females (18-71 years) was studied. Elisa method was used to measure the OPG, RANKL and the leptin, adiponectin levels in females’ serum. Results: OPG values were inversely correlated with leptin (rho = -0.38, p = 0.002) and positively correlated with age (rho = 0.27, p=0.01) and body mass index (rho = 0.29, p=0.009). RANKL values were inversely correlated with adiponectin (rho = -0.23, p = 0.06) and age (rho = -0.30, p=0.01). Additionally, OPG was higher in post- as compared to pre-menopausal women. Further data analysis adjusting for potential confounders revealed that the OPG/RANKL ratio was positively associated with adiponectin and inversely associated with leptin levels independent of the effect of age, body mass index and menopausal status. Conclusions: These results reveal that leptin circulating levels are inversely associated with serum OPG/RANKL ratio among healthy women.

Rapid vinculin exchange dynamics at focal adhesions in primary osteoblasts following shear flow stimulation.

Abstract: The adaptor protein vinculin plays a key position in the formation of focal adhesions and regulates cell attachment. To study the turnover of vinculin in bone-derived cells, we expressed green fluorescent protein-tagged vinculin in primary bovine osteoblasts and examined the appearance of focal adhesions in cells exposed to laminar shear flow. Already 20 sec after application of shear stress fluorescently labelled focal adhesions became visible as small flashing dots at the periphery of cells. The number of newly formed focal adhesions per individual cell increased continuously over approximately 300 sec and then remained relatively stable. The assembly of focal adhesions in shear stress-stimulated osteoblasts was accompanied by a transient rise in intracellular calcium levels. The mean assembly time of an individual focal adhesion plaque was 32.2±2.2 sec and the mean disassembly time was 60.5±6.0 sec. The recruitment of vinculin to nascent focal adhesions was in the same range as the recovery half-life of GFP-vinculin at stable focal adhesions (13.0±2.0 sec). These data show that accumulation of GFP-vinculin in newly formed focal adhesions and its exchange from pre-existing, mature plaques are both rapid processes that occur in mechanically stimulated osteoblasts within less than one minute.

Effects of oxidation on the power of chemically skinned rat soleus fibres

Abstract: Oxidation alters calcium sensitivity, and decreases maximum isometric force (Po) and shortening velocity (Vmax) of single muscle fibres. To examine the effect of oxidation on the curvature of the force-velocity relationship, which determines muscle power in addition to Po and Vmax, skinned rat type I fibres were maximally activated at 15oC in a solution with pCa 4.5 and subjected to isotonic contractions before and after 4-min incubation in 50 mM H2O2 (n=10) or normal relaxing solution (n=3). In five oxidised and four control fibres the rate of force redevelopment (ktr), following a rapid release and re-stretch, was measured. This gives a measure of the sum of the rate constants for cross-bridge attachment (f) and detachment (g1): (f+g1). H2O2 reduced Po, Vmax and ktr by 19%, 21% and 24% respectively (P<0.001), while the shape of the force-velocity relationship was unchanged. Fitting data to the Huxley cross-bridge model suggested that oxidation decreased both the rate constant for cross-bridge attachment (f), and detachment of negatively strained cross-bridges (g2), similar to the effect of reduced activation 1 . This suggests that oxidative modification is a possible cause of the variation in contractile properties between muscle fibres of the same type 2 .

Musculoskeletal symptoms and neurological investigations in adrenocortical insufficiency: a case report and literature review.

Abstract: Objectives Various forms of adrenocortical insufficiency can cause musculoskeletal symptoms such as muscle pain, tautness of the limbs, arthralgia, and flexion contractures. However, the findings of neurological investigations are inconclusive and have not been well summarized. Methods We report the case of a 61-year-old man with isolated adrenocorticotropic hormone deficiency who presented with musculoskeletal symptoms, including flexion contractures. We performed three neurological investigations: nerve conduction studies, electromyography, and muscle biopsy analysis. Further, we reviewed reports of 16 patients with various forms of adrenocortical insufficiency and musculoskeletal symptoms by considering the findings of these three investigations. Results From the literature review, we found that (a) analysis of muscle biopsy is the most sensitive technique, followed by electromyography and then nerve conduction studies; and (b) the longer the duration of the musculoskeletal symptoms, the greater the incidence of abnormal findings with all three techniques. Conclusions Physicians may prioritize neurological investigations, depending on these findings.

A novel tongue implant for tongue advancement for obstructive sleep apnea: feasibility, safety and histology in a canine model.

Abstract: Obstructive sleep apnea (OSA) is a sleep related breathing disorder caused by partial or complete collapse of the upper airway during sleep. The disease is linked with important cardiovascular and cerebrovascular morbidity and mortality. Tongue base collapse is a major cause of upper airway occlusion in OSA and present surgical procedures to prevent this are invasive and inefficient. A novel implantable system to stabilize the tongue was evaluated in a canine model for feasibility, safety and histology. Successful implantation of the Advance System was performed in 21 canines and follow-up evaluations were performed at 30, 60, 90, 120 and 150 days. No technical or clinical adverse events were seen during the procedure. Minor clinical adverse events at some of the follow-up evaluations were treated successfully. Histologic evaluation of the implant was performed at different time points during follow-up and showed good biocompatibility, stability and osteointegration. The outcome of this study resulted in an implant for adjustable tongue advancement in humans with OSA.