Objectives: The present study sought to determine the effects of decreased peripheral sensory nerve function on skeletal development and bone metabolism in mice. Methods: C57BL/6 neonatal mice were treated with capsaicin to induce peripheral sensory nerve degeneration, and compared to vehicle-treated controls at 4, 8 and 12 weeks of age. Changes in bone structure were assessed using micro-computed tomography, mechanical properties and fracture resistance were assessed using three-point bending of radii, and bone turnover was assessed using dynamic histomorphometry and serum biomarkers. Results: Capsaicin treatment resulted in small but significant decreases in bone structure, particularly affecting trabecular bone. Capsaicin-treated mice exhibited lower trabecular thickness at the femoral metaphysis and L5 vertebral body compared with vehicle-treated mice. However, capsaicin- and vehicle-treated mice had similar mechanical properties and bone turnover rates. Conclusion: Neonatal capsaicin treatment affected trabecular bone during development; however these small changes may not be meaningful with respect to bone strength under normal loading conditions. It is possible that capsaicin-sensitive neurons may be more important for bone under stress conditions such as increased mechanical loading or injury. Future studies will investigate this potential role of peripheral sensory nerves in bone adaptation.

Objectives: This study examined individual and combined effects of the cancer treatments goserelin acetate (GA) and doxorubicin (DOX) on bone and determined if treadmill running (TM) provides osteoprotection. Methods: Ten-week-old female Sprague-Dawley rats were randomly assigned to sedentary (SED) or TM groups. SED received GA, DOX, combined GA and DOX (GA+DOX), or placebo and maintained normal cage activity. TM received GA, DOX, GA+DOX, or placebo and participated in a progressive motorized treadmill protocol. After 8 weeks, tibiae were evaluated using micro computed tomography. Results: Negative drug effects were observed in cancellous bone (bone volume/tissue volume, trabecular number, trabecular thickness, trabecular spacing; P<0.05). An additive bone volume/tissue volume and trabecular spacing effect was observed in SED GA+DOX (vs. SED+GA and SED+DOX, P<0.05) but not in TM GA+DOX (vs. TM+GA and TM+DOX, P>0.05). Negative drug effects were observed in cortical bone (cross-sectional volume, cortical volume, marrow volume; P<0.05), but combined GA+DOX did not exacerbate these effects. Additionally, there were no protective cortical bone effects observed in TM. Conclusions: Combined GA+DOX exacerbates cancellous osteopenia in the tibia, and treadmill running provided only minor protection.

Objectives: To identify the prevalence and risk factors in the development of Neurogenic Heterotopic Ossification (NHO) in traumatic brain and spinal cord injured patients admitted to specialised units. Methods: An audit protocol was used to gather all clinically relevant data, in specific patient groups, relating to the prevalence of NHO, and was statistically analysed to identify traumatic brain injury (TBI) and traumatic spinal cord injury (TSCI) patients at high risk of developing NHO. Results: 262 TBI and 151 TSCI patients were identified. NHO was diagnosed in 10 and 16 patients with TBI and TSCI, respectively; 18 clinically relevant characteristics were analysed for association with NHO in these patient groups. The only common variables associated with NHO in both neurological conditions were deep vein thrombosis and/or pulmonary emboli (DVT/PE). Conclusions: The prevalence of NHO in TBI patients is less than one-third of that found in TSCI patients, ~4% and 11%, respectively. This study also suggests that the risk factors associated with NHO in TBI patients are distinct from those identified as risk factors in TSCI patients.

The pQCT-assessed Bone Strength Indices (BSI's, SSI) depend on the product of a "quality" indicator, the cortical vBMD (vCtD), and a "design" indicator, one of the cross-sectional moments of inertia or related variables (MIs) in long bones. As the MIs vary naturally much more than the vCtD and represent different properties, it could be that the variation of the indices might not reflect the relative mechanical impact of the variation of their determinant factors in different individuals or circumstances. To understand this problem, we determined the vCtD and MI's in tibia scans of 232 healthy men and pre- and post-MP women, expressed in SD of the means calculated for each group, and analyzed the independent influence of 1 SD unit of variation of each factor on that of the indices by multiple correlations. Results showed: 1. that the independent influence of the MIs on the indices was generally larger than that of the vCtD, and 2. that in post-MP women the influence of the vCtD was larger than it was in the other groups. This confirms the view that inter-individual variation of vCtD is comparatively small, and that mechanical competence of human bone is mostly determined by "design" factors.

Objectives: The purpose of this study was to investigate whether there is already an association of insulin resistance (IR) with muscle mass and –force/torque in an adult population and whether this relationship is the same in distal and proximal body parts. Methods: 358 Healthy young men were divided into a more insulin sensitive (MIS) (n=89) and a less insulin sensitive (LIS) group (n=89), respectively using lower and upper quartiles of HOMA-IR index (Homeostasis Model Assessment of IR). Muscle force/torque and lean mass, were compared between the two groups. Results: LIS subjects had higher absolute thigh lean mass, but not higher thigh muscle torque, resulting in a lower torque per kg muscle. In upper arm, lean mass was higher in LIS subjects, but also absolute muscle torque resulted higher. For handgrip force, the LIS and MIS group had similar results, despite a trend towards higher forearm lean mass in LIS subjects. Lean mass % of total lean mass is lower in LIS subjects in more distal body parts. Conclusions: Already in a young healthy population, IR seems to be associated with lower force/torque per muscle mass and lower lean mass % of total lean mass predominantly in more distal body parts.

We investigated the effects of eccentric contractions (ECs) on bone metabolism markers and the relationship between bone metabolism and skeletal muscle related protein. Seventeen young untrained men were divided into two groups and performed either 60 or 30 maximal ECs. We measured serum levels of osteocalcin (OC), bone alkaline phosphatase, cross-linked N-telopeptide of type I collagen (NTx), and tartrate-resistant acid phosphatase 5b (TRACP-5b), growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Blood samples were collected for up to five days after ECs. OC with 60 ECs were significantly higher than with 30 ECs (2 hours; p<0.05, day 1 and day 5; p<0.01). TRACP-5b with 60 ECs were significantly higher than with 30 ECs (day 3 and day 5; p<0.001). IGF-1 and OC were significantly positively correlated with 60 ECs (2 hours, day 1, and day 5; p<0.05). There were also significant positive correlations between IGF-1 and NTx with 60 ECs (2 hours, p<0.01; day 1, p<0.05). We found that one bout of severe ECs caused increases in OC and TRACP-5b, which promote increased bone metabolism. Our results suggest that contraction-induced IGF-1 may activate OC and NTx in acute response.

Objectives: To examine the post-exercise cross-transfer effects of acute whole body vibration (WBV). Methods: Seventeen healthy male volunteers (20.8±1.2 y) performed three unilateral vibration conditions in a randomized order: 1) WBV-50 Hz [high amplitude]; 2) WBV-30 Hz [low amplitude]; and 3) a control no WBV condition (Sham) applied to the dominant leg. Each condition involved maximal voluntary isometric contractions (MVC) followed by three leg press explosive repetitions (40% MVC) with non-dominant and dominant legs; which were conducted prior to and post vibration (immediately; 2 min and 5 min). Surface electromyography (sEMG) of the vastus lateralis (VL) and medial gastrocnemius (MG) were measured throughout each condition. Results: A condition x leg x time interaction effect was detected (p=0.001) where 50 Hz-High in the stimulated leg enhanced mean velocity at post-2 min compared to 30 Hz-Low and Sham, remaining elevated at post-5 min. Similarly, 50 Hz-High in the non-stimulated leg increased mean velocity at post-immediately and post-2 min compared to 30 Hz-Low and Sham. There were no changes in sEMG of VL and GM in the stimulated and non-stimulated post-conditions. Conclusion: WBV (50 Hz) can augment cross-transfer in neuromuscular performance. WBV could provide an alternate method of unilateral training to promote cross education explosive strength.

Resistance exercise can result in localized damage to muscle tissue. This damage may be observed in sarcolemma, basal lamina, as well as, in the contractile elements and the cytoskeleton. Usually the damage is accompanied by release of enzymes such as creatine kinase (CK) and lactate dehydrogenase, myoglobin and other proteins into the blood. Serum CK has been proposed as one of the best indirect indicators of muscle damage due to its ease of identification and the relatively low cost of assays to quantify it. Thus, CK has been used as an indicator of the training intensity and a diagnostic marker of overtraining. However, some issues complicate CK’s use in this manner. There is great interindividual variability in serum CK, which complicates the assignment of reliable reference values for athletes. Furthermore, factors such as training level, muscle groups involved, and gender can influence CK levels to a greater extent than differences in exercise volume completed. This review will detail the process by which resistance exercise induces a rise in circulating CK, illuminate the various factors that affect the CK response to resistance exercise, and discuss the relative usefulness of CK as a marker of training status, in light of these factors.

We examined roles of loading and inflammation on forearm bones in a rat model of upper extremity overuse. Trabecular structure in distal radius and ulna was examined in three groups of young adult rats: 1) 5% food-restricted that underwent an initial training period of 10 min/day for 5 weeks to learn the repetitive task (TRHF); 2) rats that underwent the same training before performing a high repetition high force task, 2 hours/day for 12 weeks (HRHF); and 3) food-restricted only (FRC). Subsets were treated with oral ibuprofen (IBU). TRHF rats had increased trabecular bone volume and numbers, osteoblasts, and serum osteocalcin, indicative of bone adaptation. HRHF rats had constant muscle pulling forces, showed limited signs of bone adaptation, but many signs of bone resorption, including decreased trabecular bone volume and bone mineral density, increased osteoclasts and bone inflammatory cytokines, and reduced median nerve conduction velocity (15%). HRHF+IBU rats showed no trabecular resorptive changes, no increased osteoclasts or bone inflammatory cytokines, no nerve inflammation, preserved nerve conduction, and increased muscle voluntary pulling forces. Ibuprofen treatment preserved trabecular bone quality by reducing osteoclasts and bone inflammatory cytokines, and improving muscle pulling forces on bones as a result of reduced nerve inflammation.

The purpose of the study was to validate optical segment tracking, a new method for in vivo human tibia deformation measurements and to assess bending in a three-point bending test. The approach relies upon optical motion capturing of reflecting marker clusters affixed to the bone via screws inserted three millimeters into the corticalis in local anesthesia. The method was tested in five healthy subjects. Screws were left in place for six to eight hours and a variety of exercises performed. A pain questionnaire was used to assess pain levels. pQCT-images were taken to locate screw holes in the bone. A three-point bending test was performed and repeatability evaluated. The new method shows good feasibility though this was previously considered impossible by many experts. Local anesthesia works for screw implantation and explantation. Results show linearity with an average of 0.25 degrees per 10 kg of weight applied with good repeatability (average variation coefficient 8%). Optical segment tracking is feasible for human in vivo bone deformation measurements. There is a variety of possible clinical and experimental applications including stability testing of osteosyntheses and joints, monitoring of bone healing, evaluation of exercises in physiotherapy, and assessment of bone deformation patterns in bone disease.

Objective: To determine the in vivo precision of MRI-based measures of bone and muscle traits at the hip. Methods: Left proximal femoral neck and shaft of 14 participants (5M:9F; age:21-68) were scanned 3 times using a 1.5T MRI. Commercial and custom image processing methods were used to derive bone geometry and strength traits at the proximal femoral neck and shaft along with muscle area of various muscle groups at the shaft site. For precision, root mean square coefficients of variation (CV_rms) and standard deviations (SD_rms) were calculated. Results: At the femoral neck, CV_rms for area-based bone measures ranged between 1.7-5.0%; CV_rms for cortical thickness varied from 4.7 to 5.6%; and CV_rms for bending, torsional and buckling-based strength indices ranged between 4.6-7.1%. At the femoral shaft, CV_rms for bone area ranged between 1.2-3.0%; CV_rms for cortical thickness varied from 1.7 to 2.0%; and CV_rms for bending and buckling-based strength indices ranged between 1.4-3.1%. For muscle area, CV_rms ranged between 1.3-4.5%. Conclusions: MRI-based measures of bone and muscle traits at the proximal femoral neck and shaft demonstrated in vivo precision errors <7.1%. MRI is a promising 3D technique for monitoring changes in bone and muscle at the clinically important hip.

Objectives: This work provides a reference for future papers originating from this study by providing basic results on body mass, urine volume, and hemodynamic changes to 5 days of bed rest (BR) and by describing acute cardio-respiratory/mechanographic responses to a short versatile upright exercise battery. Methods: Ten male subjects (mean±SEM age: 29.4±1.5 years; height: 178.8±1.5 cm; body mass: 77.7±1.5 kg) performed, in random order, 5 days of 6° head-down tilt (HDT) BR with no exercise (CON), or BR with daily 25 minutes of quiet upright standing (STA) or upright locomotion replacement training (LRT). Results: Plasma volume, exercise capacity and orthostatic tolerance decreased similarly between interventions following 5 days of BR. Upright heart rate during LRT and STA increased throughout BR; from 137±4 bpm to 146±4 bpm for LRT (P<0.01); and from 90±3 bpm to 102±6 bpm (P<0.001) for STA. Conclusion: The overall similarity in the response to BR, and increase in upright heart rate during the LRT sessions suggest early and advancing cardiovascular deconditioning during 5 days of BR bed rest, which was not prevented by the versatile exercise regime.

Distraction osteogenesis (DO) is a successful technique for bone lengthening, but one problem is the need to keep an external fixator in place until bone completely regenerates. We hypothesized that the systemic administration of sclerostin antibodies (Scl-Ab) can accelerate bone regeneration in a mouse model of DO. A total of 110 mice were randomized to receive one intravenous injection per week of either Scl-Ab (100 mg per kg body weight) or saline after DO surgery. Mice were sacrificed on day 11, 17, 34 or 51 post-surgery. Microcomputed tomography showed that bone volume per tissue volume of the Scl-Ab treated group was significantly higher on day 11 (P=0.009). Histological examinations indicated that chondrocytes and fibrocartilage predominated in the Scl-Ab group at day 11. The radiographic score of bone healing was also higher in Scl-Ab treated animals at day 11. There was a trend towards higher ultimate force and work to failure in Scl-Ab treated groups on day 34 and 51 (P>0.05). These data suggest the potential utility of Scl-Ab to reduce the time during DO when an external fixator is required.

Tendinopathies are a major cause of disability in the athletic population; the main purpose of the treatment of these injuries is to reduce pain and improve function. The aim of this study was to evaluate the effect of NSAIDs on leg stiffness of patients suffering acute unilateral Achilles tendinopathy. Twenty-eight eligible male athletes (aged 39.1±10.3 y) suffering acute Achilles tendinopathy were treated with etoricoxib (120 mg oral once daily) during 7 days. Pain (100-mm visual analogue scale-VAS), analgesic effect (percentage of 100-mm VAS reduction), and leg stiffness were evaluated pre- and post- anti-inflammatory treatment. Results of this study showed that over the 7-day treatment period, etoricoxib provided significant relief of Achilles tendon pain (VAS) compared to that experienced at baseline: 54.5±21.6 and 24.5±24.8, respectively (p<0.001). Leg stiffness showed a significant improvement after one-week NSAID therapy: LSR 0.89±0.1 vs. 0.97±0.1; (p=0.02). In conclusion, findings of this study demonstrated that patients suffering acute unilateral Achilles tendinopathy increased their leg stiffness of the affected side after oral anti-inflammatory therapy. Effective control of tendon pain in the acute phase of such sports-related injuries may contribute to improve capabilities associated with high performance like leg stiffness.