Local Application of Mineral-Coated Microparticles Loaded With VEGF and BMP-2 Induces the Healing of Murine Atrophic Non-Unions.

Deficient angiogenesis and disturbed osteogenesis are key factors for the development of nonunions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2. In this study, we investigated whether a combination of VEGF- and BMP-2-loaded MCM (MCM + VB) with a ratio of 1:2 improves bone repair in non-unions. For this purpose, we applied MCM + VB or unloaded MCM in a murine non-union model and studied the process of bone healing by means of radiological, biomechanical, histomorphometric, immunohistochemical and Western blot techniques after 14 and 70 days. MCM-free non-unions served as controls. Bone defects treated with MCM + VB exhibited osseous bridging, an improved biomechanical stiffness, an increased bone volume within the callus including ongoing mineralization, increased vascularization, and a histologically larger total periosteal callus area consisting predominantly of osseous tissue when compared to defects of the other groups. Western blot analyses on day 14 revealed a higher expression of osteoprotegerin (OPG) and vice versa reduced expression of receptor activator of NF-κB ligand (RANKL) in bone defects treated with MCM + VB. On day 70, these defects exhibited an increased expression of erythropoietin (EPO), EPO-receptor and BMP-4. These findings indicate that the use of MCM for spatiotemporal controlled delivery of VEGF and BMP-2 shows great potential to improve bone healing in atrophic non-unions by promoting angiogenesis and osteogenesis as well as reducing early osteoclast activity.

T2-relaxation time increases in lumbar intervertebral discs after 21d head-down tilt bed-rest.

OBJECTIVES: Spaceflight back pain and intervertebral disc (IVD) herniations cause problems in astronauts. Purpose of this study was to assess changes in T2-relaxation-time through MRI measurements before and after head-down tilt bed-rest, a spaceflight analog. METHODS: 8 men participated in the bed-rest study. Subjects remained in 6° head down tilt bed-rest in two campaigns of 21 days, and received a nutritional intervention (potassium bicarbonate 90 mmol/d) in a cross-over design. MRI measurements were performed 2 days before bed-rest, as well as one and five days after getting up. Image segmentation and data analysis were conducted for the IVDs Th12/L1 to L5/S1. RESULTS: 7 subjects, average age of 27.6 (SD 3.3) years, completed the study. Results showed a significant increase in T2-time in all IVDs (p⟨0.001), more pronounced in the nucleus pulposus than in the annulus fibrosus (p⟨0.001). Oral potassium bicarbonate did not show an effect (p=0.443). Pfirrmann-grade correlated with the T2-time (p⟨0.001). CONCLUSIONS: 6° head-down tilt bed-rest leads to a T2-time increase in lumbar IVDs. Oral potassium bicarbonate supplementation does not have an effect on IVD T2-time.

Whey protein plus bicarbonate supplement has little effects on structural atrophy and proteolysis marker immunopatterns in skeletal muscle disuse during 21 days of bed rest.

OBJECTIVES: To investigate the effect of whey protein plus potassium bicarbonate supplement on disused skeletal muscle structure and proteolysis after bed rest (BR). METHODS: Soleus (SOL) and vastus lateralis (VL) biopsies were sampled from ten (n=10) healthy male subjects (aged 31±6 years) who did BR once with and once without protein supplement as a dietary countermeasure (cross-over study design). The structural changes (myofibre size and type distribution) were analysed by histological sections, and muscle protein breakdown indirectly via the proteolysis markers, calpain 1 and 3, calpastatin, MuRF1 and 2, both in muscle homogenates and by immunohistochemistry. RESULTS: BR caused size-changes in myofiber cross-sectional area (FCSA, SOL, p=0,004; VL, p=0.03), and myofiber slow-to-fast type transition with increased hybrids (SOL, p=0.043; VL, p=0.037) however with campaign differences in SOL (p<0.033). No significant effect of BR and supplement was found by any of the key proteolysis markers. CONCLUSIONS: Campaign differences in structural muscle adaptation may be an issue in cross-over design BR studies. The whey protein plus potassium bicarbonate supplement did not attenuate atrophy and fibre type transition during medium term bed rest. Alkaline whey protein supplements may however be beneficial as adjuncts to exercise countermeasures in disuse.

Impact of age, performance and athletic event on injury rates in master athletics - first results from an ongoing prospective study.

OBJECTIVES: Recent studies have identified rates of injuries in young elite athletes during major athletic events. However, no such data exist on master athletes. The aim of this study was to assess incidence and types of injuries during the 2012 European Veteran Athletics Championships as a function of age, performance and athletic discipline. METHODS: Report forms were used to identify injured athletes and injury types. Analysis included age (grouped in five-year bands beginning at age 35 years), athletic event, and age-graded performance. RESULTS: Of the 3154 athletes (53.2 years (SD 12.3)) that participated in the championships (1004 (31.8%) women, 2150 (68.2%) men), 76 were registered as injured; 2.8% of the female (29), 2.2% of the male (47) athletes. There were no fractures. One injury required operative treatment (Achilles tendon rupture). Injury rates were significantly higher in the sprint/middle distance/jumps than the throws, long distance and decathlon/heptathlon groups (X(2) (3)=16.187, P=0.001). There was no significant interrelationship with age (X(2) (12)=6.495, P=0.889) or age-graded performance (X(2) (3)=3.563, P=0.313). CONCLUSIONS: The results suggest that healthy master athletes have a low risk of injury that does not increase with age or performance.

In vivo measurements of human bone deformation using optical segment tracking: surgical approach and validation in a three-point bending test.

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.

Effects of age and starting age upon side asymmetry in the arms of veteran tennis players: a cross-sectional study.

UNLABELLED: While tennis playing results in large bone strength benefits in the racquet arm of young players, the effects of tennis playing in old players have not been investigated. Large side asymmetries in bone strength were found in veteran players, which were more pronounced in men, younger players and childhood starters. INTRODUCTION: Regular tennis results in large racquet arm bone and muscle strength advantages; however, these effects have not been studied in old players. The non-racquet arm can act as an internal control for the exercising racquet arm without confounding factors, e.g. genotype. Therefore, veteran tennis player side asymmetries were examined to investigate age, sex and starting age effects on bone exercise benefits. METHODS: Peripheral quantitative computed tomography (pQCT) scans were taken at the radius, ulna and humerus mid-shaft and distal radius in both arms of 88 tennis players (51 males, 37 females; mean age 63.8 ± 11.8 years). Thirty-two players began playing in adulthood, thereby termed 'old starters'; players were otherwise termed 'young starters'. RESULTS: Muscle size and bone strength were greater in the racquet arm; notably, distal radius bone mineral content (BMC) was 13 ± 10% higher and humeral bone area 23 ± 12% larger (both P < 0.001). Epiphyseal BMC asymmetry was not affected by age (P = 0.863) or sex (P = 0.954), but diaphyseal asymmetries were less pronounced in older players and women, particularly in the humerus where BMC, area and moment of resistance asymmetries were 28-34 % less in women (P < 0.01). Bone area and periosteal circumference asymmetries were smaller in old starters (all P < 0.01); most notably, no distal radius asymmetry was found in this group (0.4 ± 3.4%). CONCLUSIONS: Tennis participation is associated with large side asymmetries in muscle and bone strength in old age. Larger relative side asymmetries in men, younger players and young starters suggest a greater potential for exercise benefits to bone in these groups.

Localized nodular pigmented villonodular synovitis of the upper ankle joint--diagnosis and treatment.

This paper introduces a case of local pigmented villonodular synovits (PVNS) of the upper ankle joint in a 37-year old patient. PVNS is a neoplasia of the synovial membrane. Two different entities of PVNS are known: generalized diffuse and local nodular. They differ in their degree of destruction and growth configuration, which is crucial for prognosis and operative treatment. The most common location of the local nodular form is the knee joint, followed by the finger joints. Occurrence in the ankle joint is not common but should be considered if clinical findings are present. MRI is the method of choice for diagnosis and assessment of the bone situation. Treatment consists of radical excision of the neoplasia. Radiosynoviorthesis is recommended as a post-operative treatment to increase the probability of a total removal of persisting PVNS cells. The rate of recurrence seems to be between 8 and 46%.