The effect of strontium ranelate on the healing of a fractured ulna with bone gap in rabbit

BACKGROUND: Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination. RESULTS: Based on the x-rays and CT scans, fracture healing or bone formation was observed to be faster in the control group. From the x-ray findings, 80 % of the fracture united and by CT scan, 60 % of the fracture united in the control group at the end of the six-week study. None of the fractures united in the test group. However, the histopathology report showed that a callus of different stages was being formed in both groups, consisting of 80 % of bone. The serum levels of osteocalcin and alkaline phosphatase initially remained similar up to three weeks and changed slightly at the end of six weeks. CONCLUSIONS: We conclude that the strontium effect begins slowly, and while it may not interfere with bone cell proliferation it may interfere in the mineralization and delay the acute stage of fracture healing. We recommend that a larger sample size and a longer duration of the study period be implemented to confirm our finding

The lateral retinaculum of the knee

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The Utility of Lesser Trochanter Version to Estimate Femoral Anteversion in Total Hip Arthroplasty: A Three-Dimensional Computed Tomography Study

Objective: Femoral anteversion is an important parameter that can prevent complication following total hip arthroplasty (THA) caused by improper positioning of the implant. However, assessing the femoral anteversion can be challenging in situations with significant defect of the femoral neck. In this study, the lesser trochanter version was nominated as alternative parameter to femoral anteversion. So, the main objective of this study is to determine whether the femoral anteversion correlates with the lesser trochanter version. Design: Retrospective study. Methods: Three-dimensional images of 100 femora were generated and their femoral anteversion and lesser trochanter version was measured. Correlation between the parameters were calculated. Results: The mean lesser trochanter version was 38.54° ± 7.86° (mean ± SD), while the mean femoral anteversion was 11.84° ± 10.06°. The lesser trochanter version was inversely correlated with the femoral anteversion with a correlation coefficient of −0.72. Conclusions: The lesser trochanter should be considered as an additional bony landmark to assess proper implant positioning in THA.</jats:p

Uniaxial Cyclic Tensile Stretching at 8% Strain Exclusively Promotes Tenogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

The present study was conducted to establish the amount of mechanical strain (uniaxial cyclic stretching) required to provide optimal tenogenic differentiation expression in human mesenchymal stromal cells (hMSCs) in vitro, in view of its potential application for tendon maintenance and regeneration. Methods. In the present study, hMSCs were subjected to 1 Hz uniaxial cyclic stretching for 6, 24, 48, and 72 hours; and were compared to unstretched cells. Changes in cell morphology were observed under light and atomic force microscopy. The tenogenic, osteogenic, adipogenic, and chondrogenic differentiation potential of hMSCs were evaluated using biochemical assays, extracellular matrix expressions, and selected mesenchyme gene expression markers; and were compared to primary tenocytes. Results. Cells subjected to loading displayed cytoskeletal coarsening, longer actin stress fiber, and higher cell stiffness as early as 6 hours. At 8% and 12% strains, an increase in collagen I, collagen III, fibronectin, and N-cadherin production was observed. Tenogenic gene expressions were highly expressed (p<0.05) at 8% (highest) and 12%, both comparable to tenocytes. In contrast, the osteoblastic, chondrogenic, and adipogenic marker genes appeared to be downregulated. Conclusion. Our study suggests that mechanical loading at 8% strain and 1 Hz provides exclusive tenogenic differentiation; and produced comparable protein and gene expression to primary tenocytes

Tibia vara in Asians: Myth or fact? Verification with three-dimensional computed tomography

Background: There is a common perception among surgeons that Asian tibiae are significantly more varus compared to non-Asians, contributed both by an acute medial tibial proximal angle (MPTA) and diaphyseal bowing. Insight into the normative morphology of the tibia allows generation of knowledge towards disease processes and subsequently planning for corrective surgeries. Methods: Computed tomography (CT) scans of 100 normal adult knees, aged 18 years and above, were analysed using a 3-dimensional (3D) analysis software. All tibiae were first aligned to a standard frame of reference and then rotationally aligned to the tibial centroid axis (TCAx) and the transmalleolar axis (tmAx). MPTA was measured from best-fit planes on the surface of the proximal tibia for each rotational alignment. Diaphyseal bowing was assessed by dividing the shaft to three equal portions and establishing the angle between the proximal and distal segments. Results: The mean MPTA was 87.0° ± 2.2° (mean ± SD) when rotationally aligned to TCAx and 91.6° ± 2.7° when aligned to tmAx. The mean diaphyseal bowing was 0.1° ± 1.9° varus when rotationally aligned to TCAx and 0.3° ± 1.6° valgus when aligned to tmAx. The mean difference when the MPTA was measured with two different rotational alignments (TCAx and tmAx) was 4.6° ± 2.3°. No statistically significant differences were observed between males and females. Post hoc tests revealed statistically significant difference in MPTA between different ethnic sub-groups. Conclusion: The morphology of the proximal tibiae in the disease-free Asian knee is inherently varus but not more so than other reported populations. The varus profile is contributed by the MPTA, with negligible diaphyseal bowing. These implications are relevant to surgical planning and prosthesis design. </jats:sec

A Comparative Study on Morphochemical Properties and Osteogenic Cell Differentiation within Bone Graft and Coral Graft Culture Systems

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Identification of pathways mediating growth differentiation factor5-induced tenogenic differentiation in human bone marrow stromal cells

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Identification of Pathways Mediating Growth Differentiation Factor5-Induced Tenogenic Differentiation in Human Bone Marrow Stromal Cells.

To date, the molecular signalling mechanisms which regulate growth factors-induced MSCs tenogenic differentiation remain largely unknown. Therefore, a study to determine the global gene expression profile of tenogenic differentiation in human bone marrow stromal cells (hMSCs) using growth differentiation factor 5 (GDF5) was conducted. Microarray analyses were conducted on hMSCs cultures supplemented with 100 ng/ml of GDF5 and compared to undifferentiated hMSCs and adult tenocytes. Results of QuantiGene® Plex assay support the use and interpretation of the inferred gene expression profiles and pathways information. From the 27,216 genes assessed, 873 genes (3.21% of the overall human transcriptome) were significantly altered during the tenogenic differentiation process (corrected p<0.05). The genes identified as potentially associated with tenogenic differentiation were ARHGAP29, CCL2, integrin alpha 8 and neurofilament medium polypeptides. These genes, were mainly associated with cytoskeleton reorganization (stress fibers formation) signaling. Pathway analysis demonstrated the potential molecular pathways involved in tenogenic differentiation were: cytoskeleton reorganization related i.e. keratin filament signaling and activin A signaling; cell adhesion related i.e. chemokine and adhesion signaling; and extracellular matrix related i.e. arachidonic acid production signaling. Further investigation using atomic force microscopy and confocal laser scanning microscopy demonstrated apparent cytoskeleton reorganization in GDF5-induced hMSCs suggesting that cytoskeleton reorganization signaling is an important event involved in tenogenic differentiation. Besides, a reduced nucleostemin expression observed suggested a lower cell proliferation rate in hMSCs undergoing tenogenic differentiation. Understanding and elucidating the tenogenic differentiation signalling pathways are important for future optimization of tenogenic hMSCs for functional tendon cell-based therapy and tissue engineering

Distal Femoral Rotation Correlates With Proximal Tibial Joint Line Obliquity: A Consideration for Kinematic Total Knee Arthroplasty

Background: We hypothesized that there is a correlation between the distal femoral rotation and proximal tibial joint line obliquity in nonarthritic knees. This has significance for kinematic knee arthroplasty, in which the target knee alignment desired approximates the knee before disease. Methods: Fifty computed tomography scans of nonarthritic knees were evaluated using three-dimensional image processing software. Four distal femoral rotational axes were determined in the axial plane: the transepicondylar axis (TEA), transcondylar axis (TCA), posterior condylar axis (PCA), and a line perpendicular to Whiteside's anterior-posterior axis. Then, angles were measured relative to the TEA. Tibial joint line obliquity was measured as the angle between the proximal tibial plane and a line perpendicular to the axis of the tibia. Results: There was a strong positive correlation between PCA-TEA and tibial joint line obliquity (r = 0.68, P <.001) as well as TCA-TEA and tibial joint line obliquity (r = 0.69, P <.001). In addition, the tibial joint line obliquity and TCA-TEA angles were similar, 3.7° ± 2.2° (mean ± standard deviation) and 3.5° ± 1.7° respectively (mean difference, 0.2° ± 0.2°; P =.369). Conclusion: Both PCA-TEA and TCA-TEA strongly correlated with proximal tibial joint line obliquity indicating a relationship between distal femoral rotational geometry and proximal tibial inclination. These findings could imply that the native knee in flexion attempts to balance the collateral ligaments toward a rectangular flexion space. A higher tibial varus inclination is matched with a more internally rotated distal femur relative to the TEA