The amount of periosteal apposition required to maintain bone strength during aging depends on adult bone morphology and tissue‐modulus degradation rate

Although the continued periosteal apposition that accompanies age‐related bone loss is a biomechanically critical target for prophylactic treatment of bone fragility, the magnitude of periosteal expansion required to maintain strength during aging has not been established. A new model for predicting periosteal apposition rate for men and women was developed to better understand the complex, nonlinear interactions that exist among bone morphology, tissue‐modulus, and aging. Periosteal apposition rate varied up to eightfold across bone sizes, and this depended on the relationship between cortical area and total area, which varies with external size and among anatomical sites. Increasing tissue‐modulus degradation rate from 0% to −4%/decade resulted in 65% to 145% increases in periosteal apposition rate beyond that expected for bone loss alone. Periosteal apposition rate had to increase as much as 350% over time to maintain stiffness for slender diaphyses, whereas robust bones required less than a 32% increase over time. Small changes in the amount of bone accrued during growth (ie, adult cortical area) affected periosteal apposition rate of slender bones to a much greater extent compared to robust bones. This outcome suggested that impaired bone growth places a heavy burden on the biological activity required to maintain stiffness with aging. Finally, sex‐specific differences in periosteal apposition were attributable in part to differences in bone size between the two populations. The results indicated that a substantial proportion of the variation in periosteal expansion required to maintain bone strength during aging can be attributed to the natural variation in adult bone width. Efforts to identify factors contributing to variation in periosteal expansion will benefit from developing a better understanding of how to adjust clinical data to differentiate the biological responses attributable to size‐effects from other genetic and environmental factors. © 2012 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93512/1/1643_ftp.pd

Murine patellar tendon transplantation requires transosseous cerclage augmentation — development of a transplantation model for investigation of systemic and local drivers of healing

Background Tendon injuries are common musculoskeletal injuries that heal with scar tissue formation, often achieving reduced biomechanical and functional properties. The murine patellar tendon is a research tool that holds potential for investigating tendon healing and can be useful for exploring therapeutic strategies. Since healing is a complex process that results from the collaboration between the systemic and local tissue environment, a murine tendon transplantation model that can be applied to transgenic mice and genetic mutants would allow isolation of systemic versus local tendon factors in driving effective tendon healing. Preliminary studies have shown that transplantation with simple tendon sutures results in a proximalization of the patellar bone due to the involuntary quadriceps muscle force leading to tearing of the graft and failure of the knee extensor mechanism. To avoid this elongation of the graft, two cerclage techniques for murine patellar tendon transplantation were introduced and validated. Methods Three developed surgical techniques (no-cerclage-augmentation (NCA)), transfascial suture cerclage with encirclement of the patellar tendon (TFSC), and dual-cerclage-augmentation with a transosseous bone-to-bone cerclage through the patella bone and an additional musculotendinous cerclage (DCA)) were compared at 4 and 8 weeks macroscopically in regards to graft continuity, cerclage integrity, gap formation, and radiologically by measuring the patello-tibial distance and using a patella bone position grading system. Results The NCA group showed complete failure at 5-7 days after surgery. The TFSC has led to 69% functional failure of the cerclage. In contrast, the DCA with a has led to 78% success with improvement in patellar bone position and a similar patello-tibial distance to the naive contralateral murine knees over the time period of 8 weeks. Conclusions This study shows that a bone-to-bone cerclage is necessary to maintain a desired graft length in murine patellar tendon models. This surgery technique can serve for future graft trans- and implantations in the murine patellar tendon

Podmaniczky Frigyes levele Arany Jánosnak

Tendinopathy is a common and progressive musculoskeletal disease. Increased apoptosis is an end-stage tendinopathy manifestation, but its contribution to the pathology of the disease is unknown. A previously established in vivo model of fatigue-damage accumulation shows that increased apoptosis is correlated with the severity of induced tendon damage, even in early onset of the disease, supporting its implication in the pathogenesis of the disease. Consequently, this study aimed to determine: (1) whether apoptosis could be inhibited after fatigue damage and (2) whether its inhibition could lead to remodeling of the extracellular matrix (ECM) and pericellular matrix (PCM), to ultimately improve the mechanical properties of fatigue-damaged tendons. The working hypothesis was that, despite the low vascular nature of the tendon, apoptosis would be inhibited, prompting increased production of matrix proteins and restoring tendon mechanical properties. Rats received 2 or 5 d of systemic pan-caspase inhibitor (Q-VD-OPh) or dimethyl sulfoxide (DMSO) carrier control injections starting immediately prior to fatigue loading and were sacrificed at days 7 and 14 post-fatigue-loading. Systemic pan-caspase inhibition for 2 d led to a surprising increase in apoptosis, but inhibition for 5 d increased the population of live cells that could repair the fatigue damage. Further analysis of the 5 d group showed that effective inhibition led to an increased population of cells producing ECM and PCM proteins, although typically in conjunction with oxidative stress markers. Ultimately, inhibition of apoptosis led to further deterioration in mechanical properties of fatigue-damaged tendons

Tendon overload results in alterations in cell shape and increased markers of inflammation and matrix degradation

Tendon injury is thought to involve both damage accumulation within the matrix and an accompanying cell response. While several studies have characterized cell and matrix response in chronically injured tendons, few have assessed the initial response of tendon to overload-induced damage. In this study, we assessed cell response to cyclic loading. Fascicle bundles from the equine superficial digital flexor tendon were exposed to cyclic loading in vitro, designed to mimic a bout of high-intensity exercise. Changes in cell morphology and protein-level alterations in markers of matrix inflammation and degradation were investigated. Loading resulted in matrix damage, which was accompanied by cells becoming rounder. The inflammatory markers cyclooxygenase-2 and interleukin-6 were increased in loaded samples, as were matrix metalloproteinase-13 and the collagen degradation marker C1,2C. These results indicate upregulation of inflammatory and degradative pathways in response to overload-induced in vitro, which may be initiated by alterations in cell strain environment because of localized matrix damage. This provides important information regarding the initiation of tendinopathy, suggesting that inflammation may play an important role in the initial cell response to tendon damage. Full understanding of the early tenocyte response to matrix damage is critical in order to develop effective treatments for tendinopathy

The association between retraction of the torn rotator cuff and increasing expression of hypoxia inducible factor 1α and vascular endothelial growth factor expression: an immunohistological study

<p>Abstract</p> <p>Background</p> <p>Differing levels of tendon retraction are found in full-thickness rotator cuff tears. The pathophysiology of tendon degeneration and retraction is unclear. Neoangiogenesis in tendon parenchyma indicates degeneration. Hypoxia inducible factor 1α (HIF) and vascular endothelial growth factor (VEGF) are important inducers of neoangiogenesis. Rotator cuff tendons rupture leads to fatty muscle infiltration (FI) and muscle atrophy (MA). The aim of this study is to clarify the relationship between HIF and VEGF expression, neoangiogenesis, FI, and MA in tendon retraction found in full-thickness rotator cuff tears.</p> <p>Methods</p> <p>Rotator cuff tendon samples of 33 patients with full-thickness medium-sized rotator cuff tears were harvested during reconstructive surgery. The samples were dehydrated and paraffin embedded. For immunohistological determination of VEGF and HIF expression, sample slices were strained with VEGF and HIF antibody dilution. Vessel density and vessel size were determined after Masson-Goldner staining of sample slices. The extent of tendon retraction was determined intraoperatively according to Patte's classification. Patients were assigned to 4 categories based upon Patte tendon retraction grade, including one control group. FI and MA were measured on standardized preoperative shoulder MRI.</p> <p>Results</p> <p>HIF and VEGF expression, FI, and MA were significantly higher in torn cuff samples compared with healthy tissue (p < 0.05). HIF and VEGF expression, and vessel density significantly increased with extent of tendon retraction (p < 0.05). A correlation between HIF/VEGF expression and FI and MA could be found (p < 0.05). There was no significant correlation between HIF/VEGF expression and neovascularity (p > 0.05)</p> <p>Conclusion</p> <p>Tendon retraction in full-thickness medium-sized rotator cuff tears is characterized by neovascularity, increased VEGF/HIF expression, FI, and MA. VEGF expression and neovascularity may be effective monitoring tools to assess tendon degeneration.</p

Mechanical interactions between the supraspinatus and infraspinatus tendons: Effect of supraspinatus tendon tear, load, repair technique and joint position on strain in the infraspinatus and supraspinatus tendons

Rotator cuff tears are common and not well understood shoulder problems. Structural and mechanical inhomogeneity of the supraspinatus tendon complicates accurate prediction of risk of tear propagation and may impact appropriate clinical treatment. The work presented in this thesis dissertation investigates the mechanical interaction between the supraspinatus and the infraspinatus tendons as it may be critical to understanding load bearing at the glenohumeral joint. Principal strains in the infraspinatus and supraspinatus tendons of cadaveric human shoulders were calculated to evaluate whether a mechanical interaction between the supraspinatus and infraspinatus tendons exist with: (1) an increase in anterior-side full and partial-thickness supraspinatus tendon tear sizes; (2) change in glenohumeral abduction and rotation angles; (3) increase in supraspinatus tendon load; and 4) two commonly used supraspinatus tendon repairs. Results showed that a mechanical interaction between the supraspinatus and infraspinatus tendons existed such that in general, conditions that caused increase in strain in the supraspinatus tendon, such as an increase in supraspinatus tendon tear size and load, also caused an increase in strain in the infraspinatus tendon. Results also showed that joint position significantly affects the mechanical interaction between the supraspinatus and infraspinatus tendons, causing an interruption in the mechanical interactions at joint positions where humeral head contact with the tendon is minimized. Both supraspinatus tendon repair techniques equally restored the mechanical interaction between the two tendons, and mimicked the results of the intact supraspinatus tendon regarding the effect of load and joint position. Changes in infraspinatus tendon strain associated with increases in supraspinatus tendon tear size and loading may shield a torn supraspinatus tendon from further injury or have detrimental chronic effects on the infraspinatus tendon. In conclusion, the supraspinatus and infraspinatus tendons mechanically interact. The observed significant increase in maximum principal strain and decrease in minimum principal strain was concurrent in both the infraspinatus and supraspinatus tendons except when interrupted at certain joint positions