Introduction & aims. Different racial groups show variations in femoral morphometry. Femoral anteroposterior measurement and mediolateral measurement are key variables in designing femoral implant for TKR. Their aspect ratio determines the shape and mediolateral sizing for the proper patellofemoral tracking and uniform stress distribution over the resected distal femoral surface. Method. We reviewed the current literature in December 2013 in common medical databases including the Cochrane Library, PubMed and Medline. Keywords included combinations of: Anthropometry, Knee, Arthroplasty, Femur, Morphometry, Geometry. We selected papers including femoral morphometric data collected from populations of different ethnic origins. Papers covered populations in the USA, China, Germany, Thailand, Korea, India, Japan and Malaysia. Results. We have analysed femoral morphometry variables among different ethnic groups from the available data. Gross size of the resected femur can be defined in terms of antero-posterior (AP) and medio-lateral (ML) dimensions, an in the aspect ratio of femoral medio-lateral to femoral antero-posterior dimensions (fML/fAP). The Korean population showed the least value of fAP among all the groups, followed by Thai, Japanese, Indian, Malaysian and Chinese showing the increasing order among the sub-groups of Asian Population. American population shows the next higher fAP measurements from Asian population. German follows, and Arab quantify the largest value of this femoral anthropometric variable. fML varies by huge difference among male and female data in all populations. Thai, Indian, Malaysian, Arab, Japanese, Korean, German, Chinese and American; this sequence is the increasing order of fML. More trapezoid-shaped and narrower ML, this variation in female group leads to over-hang the implant for a given fAP. Generally, the aspect ratios are measured higher in these smaller female knees, and lower in larger male knees. Conclusions. Anthropometric data measuring distal femoral segment in different ethnic groups shows that the Asian population requires custom-fit implant design based on the morphological data. It would be more appropriate to introduce several medio-lateral options in sizing the implant for given antero-posterior dimensions

Introduction and Aims: Currently, multiple femoral component types and sizes exist for primary total hip arthroplasty. However, component sizes for small femoral geometry are generally not available. The purpose of this study is to present the short-term use of a femoral component with sizes that extend into small femoral morphometry applications. Method: Between November 2001 and December 2003, 20 primary THA cases and three revision THA cases were performed utilising a non-cemented, dual threaded, cone shaped (DTCS) modular femoral component manufactured in off-the-shelf sizes, which include those sizes for small femora. The components are made of CoCr and include a size ‘Z’ (19mm proximal, 9mm distal) and a size ‘Y’ (17mm proximal, 8mm distal). Both components have hydroxyapatite coating for stimulating increased bone on-growth and a modular neck allowing intra-operative adjustments of leg length, version, offset and neck length. Results: The average patient follow-up was 10 months (range 64 days to 27 months). There were 19 (83%) hips in which the ‘Z’ component was used, and four (17%) hips with the ‘Y’ component. Radiographic evaluation revealed well-fixed and positioned components with evidence of bone densing in areas in intimate contact with the DTCS component. Radiographic evidence of minor stress shielding was observed in the greater trochanter (Gruen Zone 1) and the proximal calcar/neck cut region (Gruen Zone 7). Two revision cases (8%) required the additional use of a 6cm modular extension component (MEC) to bridge a proximal femoral deficiency. Two cases (8%) required adjunctive strut allografting at the time of surgery to protect a thin or deficient femoral cortex. There were no reported postoperative complications related to the femoral component. There was no disassociation of the modular neck from the femoral stem and there was no incidence of femoral component fracture. Conclusion: While expanding component profile offerings into larger sizes is common, developing similar component designs for abnormally small femora is uncommon, beyond the scope of the materials used and only done as a ‘custom’ order. The DTCS modular femoral component used affords a versatile option when presented with cases involving small femoral morphometry. We conclude that the DTCS component in smaller sizes is promising and warranted for continued use

Introduction: Of all hip arthroplasties conducted annually, a proportion will subsequently require revision for aseptic loosening and periprosthetic osteolysis. Osteolysis may develop ‘silently’ and monitoring of patients is recommended. This should include x-rays as progressive changes in size of a lesion may indicate a potential failure. Area measurement of osteolysis has been achieved in a number of ways but with techniques that are not readily available in routine clinical practice. The aim of this study was to develop a method for routine assessment of hip arthroplasty to quantify osteolytic changes seen on x-ray, applicable by any health professional and with good inter-observer reliability.

Methods: A morphometric grid is superimposed on an object of interest and the number of test points that fall within a defined area counted. A specialized grid was developed and initial testing was conducted on twenty simulated osteolytic lesions. Subsequent testing was on thirty-five arthroplasty x-rays with evidence of osteolytic lesions. Four observers recorded the number of crosses seen over each lesion. The observers were representative of health professions and levels of experience involved in arthroplasty review.

Data was analysed for both inter-observer and test-retest reliability using the intra-class correlation coefficient and the Bland-Altman method (use of two methods provides a better estimation of accuracy).

Results: The results for intra-class correlation coefficients on both simulated and actual lesions were all excellent (range 0.90 to 0.98) as confirmed by visual representation using the Bland-Altman method.

Discussion: Regular follow-up of hip arthroplasty with x-ray ensures that changes are monitored even when symptoms are absent. We believe that this tool can improve the process through quantitative assessment of osteolytic lesions. The scientific development supports the reliability of the tool when used by a number of raters and the simplicity of application makes it a useful addition to an arthroplasty clinic.

Many reports show good results following procedures, such as intervertebral body fusion using cage or total disc replacement, that restore adequate disc height. However, there have been no references regarding the range of normal lumbar disc height in Korean adults which can be used as a standard for the implant size. The purpose of our study is to measure the lumbar disc height on radiographs in normal Korean. 132 subjects (age range 20 to 40 years) who had no previous history of low back pain and no significant finding on physical examination were enrolled. Plain lateral lumbar spine radiograph in supine position were taken. Intervertebral disc heights were measured at anterior, middle and posterior portion of each lumbar disc. The average magnification rate was 115%, and the disc heights were corrected by the magnification rate in each segment.

Lumbar disc height showed cranio-caudal pattern in both male and female groups. L4–5 disc heights were highest at anterior, middle and posterior portion in male. L4–5 disc heights were highest at middle and posterior portion in female. L5-S1 disc height was highest at anterior portion in female, but there was no statistically significant difference between L4–5 and L5-S1 disc height at anterior portion. There was no significant difference in disc height between male and female except anterior portion of L1–2 and L2–3 disc. Statistically significant decrease in disc height was not presented in overweight person at all measured site in male and female except posterior portion of L1–2 disc in male.

This research is meaningful in that it is an attempt to provide a reference value of lumbar disc height in Korean adults, and the measured values may also be useful in manufacturing Korean modeled artificial lumbar disc prosthesis or surgical instruments for lumbar interbody fusion.

The growing interest in the development of spinal implants has led to an increasing need for biomechanical studies. Porcine spines are commonly used in such studies. Quantitative data of the normal porcine tho-racolumbar spine is lacking, yet these data are crucial to discussion of such studies. In this study we aim to provide such a database to highlight the differences between the porcine and human specimen with a view to help plan future studies contemplating their use.

6 adult (18-24 month old, 60-80 kilograms) male porcine spines were dissected of soft tissue. The lowest thoracic and all the lumbar vertebrae were studied (n=42). 15 anatomical parameters from each vertebra were measured by 2 independent observers using digital calipers (Draper PVC150D, accuracy ± 0.03mm). The mean, SD and SEM were calculated using Micro-soft Excel. Results were compared with available data on human vertebra (Zindrick et al 1987;Panjabi et al 1991,1992; Kumar et al 2000).

The inter class correlation coefficient for the observers was 0.997. The intra-observer agreement was statistically robust (0.994). The vertebral body height of the porcine vertebra was larger while both the upper and lower endplate depth and width were smaller than the human specimens. The pedicle width and depth was greater than the human specimen. The spinal canal length and depth of the porcine spine were smaller than humans indicating a narrow spinal canal. The spinous process length showed an increase from T16 to L1. This was in contrast to human spinous process. The results for the measured parameters and their comparison to human specimen will be presented.

Results from our study provides a database of anatomical measurements for the porcine vertebrae and highlights the differences with the human specimen. The data would help design future studies contemplating the use of pig spines. Biomechanical studies involving interbody cages, disc replacements and pedicle screw systems should take into account the differences and match implant size accordingly. It also provides valuable information for geometric and Finite Element Modelling of the porcine spine. Further, the results are useful in extrapolation of data from experiments which have used the porcine model.

Assessment of the appropriateness of tendon transfer procedures and the necessity for excising the posterior tibial tendon (PTT) in stage II PTT dysfunction.

12 patients undergoing surgical treatment for unilateral PTT dysfunction underwent magnetic resonance imaging of the tibialis posterior (TP) and flexor digitorum longus (FDL) muscle bellies.

All patients had atrophy of the TP muscle compared to the normal leg (mean 10.7%, p = 0.008). In those patients with a complete rupture of PTT there was replacement of the TP muscle by fatty infiltration. Conversely, the FDL muscle showed a compensatory hypertrophy (mean 17.2%, p< 0.002).

Treatment of stage II posterior tibial tendon (PTT) dysfunction remains controversial. These findings support the use of FDL as the tendon of choice for augmentation of PTT in stage II disease. This study also demonstrates that in the presence of a complete rupture, excision of the PTT is a reasonable surgical procedure and pure tenodesis will fail because the TP muscle belly undergoes fatty infiltration. In patients with a diseased but intact PTT there was no fatty infiltration and the TP muscle volume was at least 83% of the normal side in all cases. We therefore suggest that in the presence of an intact PTT the TP muscle may provide some useful function if used to augment the FDL transfer when the diseased tendon is excised.

Pre-operative and postoperative radiographs of both hips and pelvis of 160 Malaysian and Australian patients who had undergone Total Hip Replacement (THR) were reviewed.

The purpose of the study was to determine morphometric differences in each group that could influence sizing and positioning of cemented total hip implants.

In order to measure distances and diameters, we used OSIRIS, a digital radiographic analysis tool provided on the internet by the Department of Medical Imaging, University of Geneva.

The known head sizes of the implants were used to calibrate OSIRIS.

The patient groups were subdivided into three. We discovered that in general the sizes of the Malaysian population began 1 size below that of the Australian patients.

The dimensionally larger 2 groups of the Malaysian patients were similar to the smaller 2 groups of the Australian population leaving a group of small Malaysian femora for whom there were fewer suitable implants

We conclude that more work needs to be done to provide suitable implants for South East Asian patients.

Introduction: Observation of sub-clinical neurological abnormalities has led to the proposal of a neuro-developmental etiologic model for adolescent idiopathic scoliosis (AIS). We have previously demonstrated prolonged latency in somatosensory evoked potentials (SSEP) and impaired balance control in subjects with AIS. Furthermore we have compared regional brain volumes in right thoracic AIS subjects and normal controls. Significant neuro-anatomic regional differences were observed in the corpus callosum, premotor cortex, proprioceptive and visual centers of the AIS subjects compared to control subjects. Most of these regional differences involved the brain unilaterally, indicating there may be abnormal asymmetrical development in the brain of subjects with right thoracic AIS.

Methods: Following ethical committee approval a total of 29 subjects with AIS were recruited. Patients with congenital, neuromuscular or syndromic scoliosis were excluded from the study. Twenty-eight age- and sex-matched controls were recruited from local schools. All recruits underwent three-dimensional isotropic magnetization prepared rapid acquisition gradient echo (3D_MPRAGE) magnetic resonance (MR) imaging of the brain. Modern morphometric analyses of the MR images were carried out including classification of tissue into grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Tissue densities were compared between AIS subjects and controls. Comparisons were made between those subjects with left thoracic AIS (n=9) and age and sex-matched controls (n=11) and those subjects with right thoracic AIS (n=20) and age and sex-matched controls (n=17).

Results: For subjects with left thoracic curves the mean Cobb angle was 19 degrees. For subjects with right thoracic curves the mean Cobb angle was 33.8 degrees There was no significant differences observed between AIS subjects and normal controls when comparing both absolute and relative (i.e. adjusted for brain size) volumes of GM and WM. However voxel-based morphometric analysis identified significant differences in the density of WM in the genu of the corpus callosum, the left internal capsule and WM underlying the left orbitofrontal cortex when comparing those subjects with left thoracic scoliosis to controls. The above differences were not not observed when those subjects with right thoracic scoliosis were compared to controls..

Discussion: This controlled study of regional brain tissue density has demonstrated important differences in the corpus callosum, the left internal capsule and the left orbitofrontal cortex when the brain of those subjects with left thoracic scoliosis is compared to age and sex matched controls. In this study significant regional brain differences have not been identified in those subjects with right thoracic scoliosis. Further studies are warranted to ascertain whether these morphologial differences in the brain are linked with the etiopathogenisis of left sided thoracic scoliosis. A larger sample and a longitudinal study are required to establish whether brain abnormalities are predictive of curve progression.

Introduction: Low-intensity pulsed ultrasound stimulation (LIPUS) can enhance bone regeneration and callus healing during fracture repair. However, whether a certain phase of the healing process in fracture repair in particular is infiuenced by LIPUS treatment remains unclear. In this investigation, the effect of LIPUS on callus remodeling in a gap healing model was evaluated by bone morphometric analyses using 3-dimensional (3D) quantitative micro computed tomography (μCT) at the healing site, providing information on the temporal sequence of mineralized remodeling events that characterize the gap healing.

Materials and Methods: The rabbit osteotomy model with 2-mm gap for the right tibia was immobilized with four pins fixed to an external fixator with double side bars. LIPUS was continued for both the treatment group (n=7/group/time point) and the control group (n=7/group/time point), for 20 min, six times/week, for 4, 6, or 8 weeks. The control group also received a sham inactive transducer under exactly the same condition as the LIPUS group. After the harvested tibia was scanned by μCT, region of interest was set at the callus healing area. It defined as a center of the osteotomy gap with a width of 1 mm. Morphometric parameters used for evaluation were mineralized callus volume (BV, cm³) and volumetric bone mineral density of mineralized tissue comprising the callus (mBMD, mBMD = BMC/ BV, mgHA/cm³). The whole ROI was measured and was subdivided into three zones. The periosteal callus zone (External), the medullary callus zone (Endosteal) and the remaining zone was the cortical gap zone (Intercortical). For each zone, BV and mBMD were measured. Data of the μCT evaluations were analyzed using a one-way ANOVA test. Statistically significant difference was set at p < 0.05.

Results: In the LIPUS groups, BV for the Endosteal zone was significantly lower for the 8-week group than for the 4-week group. Comparing results at the same time point, the LIPUS group at 8 weeks was significantly higher than that of the control group in the Intercortical zone. As for mBMD, in the LIPUS group, the 8-week group was significantly higher than the 4-week group for Total, External, Internal, and Endosteal zones, respectively. Comparing results at the same time point, mBMD was significantly higher for the LIPUS group at 8 weeks than for the control group in both External and Intercortical zones.

Discussion: The most striking finding in our study was that LIPUS accelerated bone formation in the Intercortical zone and callus resorption in the Endosteal zone. This suggests that LIPUS could shorten the time required for remodeling. However, the results of this study do not clarify whether an early phase in callus formation in particular is infiuenced by LIPUS.

While cell morphology has been recognized as a fundamental regulator of cell behavior, few studies have measured the complex cell morphological changes of chondrocytes using quantitative cell morphometry descriptors in relation to inflammation and phenotypic outcome. Acute vs. persistent exposure to IL-1β and how IL-1β modulated dynamic changes in cell morphology in relation to the phenotype, donor and OA grade in healthy and osteoarthritis (OA) chondrocytes was investigated. A panel of quantitative cell morphometry descriptors was measured using an automated high-throughput method. Absolute quantification of gene expression was measured by ddPCR followed by correlation analyses. In OA chondrocytes, chronic IL-1β significantly decreased COL2A1, SOX9, and ACAN, increased IL-6 and IL-8 levels and caused chondrocytes to become less wide, smaller, longer, slimmer, less round and more circular, consistent with a de-differentiated phenotype. In healthy chondrocytes, 3 days after acute (72 h) IL-1β exposure, COL1A2 and IL-6 significantly increased but had minor effects on cell morphology. However, in healthy chondrocytes, persistent IL-1β led to more profound effects in all cell morphology descriptors and chondrocytes expressed significantly less COL2A1 and more IL-6 and IL-8 vs. controls and acutely-stimulated chondrocytes. In both OA and healthy chronically-stimulated chondrocytes, area, width and circularity were sensitive to the persistent presence of the IL-1β cytokine. Moreover, there were many significant and strong correlations among the measured parameters, with several indications of an IL-1β-mediated mechanism. Cell morphology combined with gene expression analysis could guide researchers interested in understanding inflammatory effects in the complex domain of cartilage/chondrocyte biology. Use of quantitative cell morphometry could complement classical approaches by providing numerical data on a large number of cells, thereby providing a biological fingerprint for describing chondrocyte phenotype, which could help to understand how changes in cell morphology lead to disease progression

Introduction. Surgeons fixing scaphoid fractures need to be familiar with its morphological variations and their implications on safe screw placement during fixation of these fractures. Literature has limited data in this regard. The purpose of this CT-based study was to investigate scaphoid morphometry and to analyse the safe trajectories of screw placement in scaphoid. Methods. We measured the coronal and Sagittal widths of scaphoid in CT-scans of 60 patients using CT based data from 50 live subjects with intact scaphoid. Safe placements for screws with diameters of 1.7mm, 2.4mm, 3.5mm and 4mm were studied using trajectories with additional 2mm safety corridor. Results. The mean width of proximal segment in coronal and sagittal plane were 6.39mm (4.5–8.7) and 11.44mm (8.4–14.1) respectively. For the waist region, the mean coronal, sagittal width were 8.03mm (6.3–10.2mm) and 9.02mm (7–11.4mm) respectively. For distal segment, the mean coronal and sagittal width were 10.58mm (8.2–14.6mm) and the 9.59mm (7.3–11.9mm) respectively. The coronal and sagittal widths were significantly different from each other in all three zones. All scaphoid were capable of safely containing single 4mm screw and two parallel 1.7mm screws. Conclusion. Our study shows that there is considerable variation in scaphoid morphometry. Among the parameters, the waist region measurements show the least variation. The screw lengths do not always correlate to the overall longitudinal extent of scaphoid and can be planned preoperatively using CT-scans. Surgeons treating these fractures should opt for a CT-based analysis regarding the screw direction and length and need to be familiar with the variations in scaphoid morphometry

Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass. Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR. Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment. Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons

Objectives. This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. Methods. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software. Results. There were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp. Conclusions. Micro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models. Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262

Introduction and Objective. Forced external rotation is hypothesized as the key mechanism of syndesmotic ankle injuries. This complex trauma pattern ruptures the syndesmotic ligaments and induces a three-dimensional deviation from the normal distal tibiofibular joint configuration. However, current diagnostic imaging modalities are impeded by a two-dimensional assessment, without taking into account ligamentous stabilizers. Therefore, our aim is two-fold: (1) to construct an articulated statistical shape model of the normal ankle with inclusion of ligamentous morphometry and (2) to apply this model in the assessment of a clinical cohort of patients with syndesmotic ankle injuries. Materials and Methods. Three-dimensional models of the distal tibiofibular joint were analyzed in asymptomatic controls (N= 76; Mean age 63 +/− 19 years), patients with syndesmotic ankle injury (N = 13; Mean age 35 +/− 15 years), and their healthy contralateral equivalent (N = 13). Subsequently, the statistical shape model was generated after aligning all ankles based on the distal tibia. The position of the syndesmotic ligaments was predicted based on previously validated iterative shortest path calculation methodology. Evaluation of the model was described by means of accuracy, compactness and generalization. Canonical Correlation Analysis was performed to assess the influence of syndesmotic lesions on the distal tibiofibular joint congruency. Results. Our presented model contained an accuracy of 0.23 +/− 0.028 mm. Mean prediction accuracy of ligament insertions was 0.53 +/− 12 mm. A statistically significant difference in anterior syndesmotic distance was found between ankles with syndesmotic lesions and healthy controls (95% CI [0.32, 3.29], p = 0.017). There was a significant correlation between presence of syndesmotic injury and the morphological distal tibiofibular configuration (r = 0.873, p <0,001). Conclusions. In this study, we constructed a bony and ligamentous statistical model representing the distal tibiofibular joint Furthermore, the presented model was able to detect an elongation injury of the anterior inferior tibiofibular ligament after traumatic syndesmotic lesions in a clinical patient cohort

Chronic glucocorticoid use causes osteogenesis loss, accelerating the progression of osteoporosis. Histone methylation is shown to epigenetically increase repressive transcription, altering lineage programming of mesenchymal stem cells (MSC). This study is undertaken to characterize the action of histone demethylase UTX to osteogenic lineage specification of bone-marrow MSC and bone integrity upon glucocorticoid treatment. Bone-marrow MSC were incubated in osteogenic medium containing supraphysiological dexamethasone. Osteogenic gene expression and mineralized nodule formation were probed using RT-PCR and von Kossa staining. The enrichment of trimethylated lysine 27 at histone 3 (H3K27me3) in Dkk1 promoter was quantified using chromatin immunoprecipitation-PCR. Bone mass and trabecular morphometry in methylprednisolone-treated skeletons were quantified using microCT analysis. Supraphysiological dexamethasone decreased osteogenic genes Runx2 and osteocalcin expression and mineralized matrix production along with reduced UTX expression in MSC. Forced UTX expression attenuated the glucocorticoid-mediated loss of osteogenic differentiation, whereas UTX knockdown provoked osteogenesis loss and cytoplasmic oil overproduction. UTX demethylated H3K27 and reduced the glucocorticoid-mediated the H3K27 enrichment in Dkk1 promoter, reversing beta-catenin signal, but downregulating Dkk1 production by MSC. In vivo, treatment with UTX inhibitor GSK-J4 significantly suppressed bone mineral density, trabecular volume, and thickness along with porous trabecular, fatty marrow and disturbed beta-catenin/Dkk1 histopathology comparable with glucocorticoid-induced osteoporosis condition. This study offers a productive insight into how UTX protects MSC from methylated histone-mediated osteogenesis repression in the development of glucocorticoid-induced osteoporosis

Introduction and Objective. In multiple trauma patients, as well as in the healing of isolated fractures (Fx) with heavy bleeding (trauma haemorrhage, TH), complications occur very often. This is particularly evident in elderly patients over 65 years of age. Since these accompanying circumstances strongly influence the clinical course of treatment, the influence of age on bone regeneration after femoral fracture and severe blood loss was investigated in this study. Materials and Methods. 12 young (17–26 weeks) and 12 old (64–72 weeks) male C57BL / 6J mice per group were examined. The fracture group Fx underwent an osteotomy after applying an external fixator. The THFx group also received blood pressure-controlled trauma hemorrhage (35 mmHg for 90 minutes) and reperfusion with Ringer's solution for 30 minutes. The Sham group received only the catheter and one external fixator. μCT scans of the femora were performed in vivo after 2 weeks and ex vivo after 3 weeks. Histological and biomechanical examinations were also carried out. The statistical significance was set at p ≤ 0.05. The non-normally distributed data were analyzed using the Mann-Whitney-U or Kruskal-Wallis test. Results. The histology showed less mineralized bone in the fracture gap in old animals of the Fx (25.41% [1.68%]) and THFx groups (25.50% [4.07%]) compared with the young ones (34.20% [6.36%], p = 0.003; 34.31% [5.12%], p=0.009). Moreover, a severe blood loss lead to more cartilage in both young (6.91% [5.08%]) and old animals (4.17% [1.42%]) compared to animals with only a fracture (2, 45% [1.04%], p=0.004; 2.95% [1.12%], p=0.032). In old animals (11.37 / nm. 2. [17.17 / nm. 2. ]) in contrast the young mice with an isolated fracture (33.6/nm. 2. [8.83/nm. 2. ]) fewer osteoclasts were present (p=0.009). Therefore, the severe blood loss further reduced the number of osteoclasts only in young animals (16.83/nm. 2. [6.07/nm. 2. ]) (p=0.004). In the in vivo μCT, after 2 weeks, a lower volume of bone, cortex and callus was found in old THFx animals (3.14 mm. 3. [0.64 mm. 3. ]); 1.01 mm. 3. [0.04 mm. 3. ]; 2.07 mm. 3. [0.57 mm. 3. ]) compared with the Fx animals (4.29 mm. 3. [0.74 mm. 3. ], p=0.008; 1.18 mm. 3. [0, 25 mm. 3. ], p=0.004; 3.02 mm. 3. [0.77 mm. 3. ], p=0.008) After 3 weeks, the ex vivo μCT scans also showed a reduced callus percentage in old THFx animals (61.18% [13.9 9%]), as well as a low number of trabeculae (1.81 mm. -1. [0.23 mm. -1. ]) compared to animals without blood loss (68.72% [15.71%], p = 0.030; 2.06mm. -1. [0.37mm. -1. ], p=0.041). In the biomechanical test, a reduced elasticity limit of the old THFx mice (7.75 N [3.33 N]) in contrast to the old Fx (10.24 N [3.32 N]) animals was shown (p=0.022). Conclusions. A severe blood loss has a higher negative effect on the healing, morphometry, and biomechanical properties of previously fractured femora in old compared to young individuals

Trochlear dysplasia is a specific morphotype of the knee, characterized by but not limited to a specific anatomy of the trochlea. The notch, posterior femur and tibial plateau also seem to be involved. In our study we conducted a semi-automated landmark-based 3D analysis on the distal femur, tibial plateau and patella. The knee morphology of a study population (n=20), diagnosed with trochlear dysplasia and a history of recurrent patellar dislocation was compared to a gender- and age-matched control group (n=20). The arthro-CT scan-based 3D-models were isotropically scaled and landmark-based reference planes were created for quantification of the morphometry. Statistical analysis was performed to detect shape differences between the femur, tibia and patella as individual bone models (Mann-Whitney U test) and to detect differences in size agreement between femur and tibia (Pearson's correlation test). The size of the femur did not differ significantly between the two groups, but the maximum size difference (scaling factor) over all cases was 35%. Significant differences were observed in the trochlear dysplasia (TD) versus control group for all conventional parameters. Morphometrical measurements showed also significant differences in the three directions (anteroposterior (AP), mediolateral (ML), proximodistal (PD)) for the distal femur, tibia and patella. Correlation tests between the width of the distal femur and the tibial plateau revealed that TD knees show less agreement between femur and tibia than the control knees; this was observed for the overall width (TD: r=0.172; p=0.494 - control group: r=0.636; p=0.003) and the medial compartment (TD: r=0.164; p=0.516 - control group: r=0.679; p=0.001), but not for the lateral compartment (TD: r=0.512; p=0.029 - control: r=0.683; p=0.001). In both groups the intercondylar eminence width was strongly correlated with the notch width (TD: r=0.791; p=0.001 - control: r=0.643; p=0.002). The morphology of the trochleodysplastic knee differs significantly from the normal knee by means of an increased ratio of AP/ML width for both femur and tibia, a smaller femoral notch and a lack of correspondence in mediolateral width between the femur and tibia. More specifically, the medial femoral condyle shows no correlation with the medial tibial plateau

It has been previously shown that Low-Magnitude High-Frequency Vibration (LMHFV) is able to enhance ovariectomy-induced osteoporotic fracture healing in rats. Fracture healing begins with the inflammatory stage, and all subsequent stages are regulated by the infiltration of immune cells such as macrophages and the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Therefore, the aim of this study was to investigate the effect of LMFHV treatment on the inflammatory response in osteoporotic fracture healing. In this study, ovariectomy-induced osteoporotic and sham-operated closed-femoral fracture SD-rats were randomized into three groups: sham control (SHAM), ovariectomized control (OVX-C) or ovariectomized vibration (OVX-V) (n=36, n=6 per group per time point). LMHFV (35Hz, 0.3g) was given 20 min/day and 5 days/week to OVX-V group. SHAM operation and ovariectomy were performed at 6-month and closed femoral fracture was performed at 9-month. Callus morphometry was determined by callus width from weekly radiography. Local expressions of inducible nitric oxide synthase (iNOS) (macrophage M1 marker), CD206 (macrophage M2 marker), TNF-α, IL-6 and IL-10 were detected by immunohistochemistry and quantified by colour threshold in ImageJ, assessed at weeks 1 and 2 post-fracture. Significant difference between groups was considered at p≤0.05 by one-way ANOVA. Callus formation was higher in OVX-V than that of OVX-C as shown by callus width at weeks 1 and 2 (p=0.054 and 0.028, respectively). Immunohistochemistry results showed that CD206 positive signal and the M2/M1 ratio which indicates the progression of macrophage polarization were significantly higher in OVX-V rats (p=0.053 and 0.049, respectively) when compared to OVX-C at week 1. Area fraction of TNF-α positive signal was significantly higher in SHAM and OVX-V rats at week 1 (p=0.01 and 0.033, respectively). IL-6 signal was also significantly higher in SHAM and OVX-V groups at week 1 (p=0.004 and 0.029, respectively). IL-10 expression was significantly lower in SHAM and OVX-V groups at week 1 (p=0.013 and 0.05, respectively). Here we have shown that LMHFV treatment promoted the shift from pro-inflammatory stage towards anti-inflammatory stage earlier. It has been reported that the polarization of pro-inflammatory macrophages M1 to anti-inflammatory macrophages M2 was indicative of the endochondral ossification process in the long bone fracture model. Besides, we found that LMHFV treatment enhanced pro-inflammatory markers of TNF-α and IL-6 and suppressed anti-inflammatory marker of IL-10 at week 1, showing that inflammatory response was enhanced at week 1 post-fracture. These inflammatory cytokines involved in fracture healing were shown to coordinate different fracture healing processes such as mesenchymal stem cell recruitment and angiogenesis. Our previous study has demonstrated that ovariectomized rats exhibit lower levels of inflammatory response after fracture creation. Therefore, we report that LMHFV treatment can modulate macrophage polarization from M1 to M2 at an earlier time-point and partly restore the impaired inflammatory response in OVX bones at the early stage of fracture healing that may lead to accelerated healing of osteoporotic fracture as shown by promoted callus formation

Introduction. Different subclinical neurological dysfunction has been reported in adolescent idiopathic scoliosis (AIS), including poor postural control and asymmetric otolith vestibulo-ocular responses when compared with normal controls. The objective of this pilot study is to establish whether abnormal MRI morphoanatomical changes arise in the CNS (brain and vestibular system), among left-thoracic versus right-thoracic AIS when compared with normal adolescent controls, with use of advanced computerised statistical morphometry techniques. Methods. We compared nine girls with left-thoracic AIS (mean age 14 years; mean Cobb angle 19°) with 11 matched controls, and 20 girls with right-thoracic AIS (mean age 15 years, mean Cobb angle 33·8°) with 17 matched controls. The statistical brain analysis was done with validated automatic segmentation and voxel-based morphometry (VBM). The T2W-MRI data for shape analysis of the vestibular system were obtained from 20 patients with right-thoracic AIS and 20 matched controls. A best-fit plane and a best-fit circle were calculated to approximate each semicircular canal. The shape of vestibular system was measured by: (1) the angle between each pair of best-fit planes; (2) the length; and (3) angle formed between the corresponding lines connecting the centres of each pair of circles. Statistical analysis was done with one-way ANOVA. Results. Patients with left-thoracic AIS had significantly lower white matter density in corpus callosum, left internal capsule, and white matter underlying orbitofrontal cortex of left hemisphere, which were not observed in patients with right-thoracic AIS. In the right-thoracic AIS group, the distance between centres of lateral and superior canals (p=0·0264) and the angle with vertex at the centre of posterior canal (p=0·02) of left-side vestibular system were significantly smaller than in the control group (figure). For vestibular analysis, there were no data for left-thoracic AIS. Conclusions. Findings from this pilot study have shown significant MRI morphoanatomical difference in CNS between patients with AIS and controls. In the brain analysis, corpus callosum (the principle commissural fibre bundle connecting left and right cerebral hemispheres, which might affect the coordination of left and right sides of the body), differed between left-thoracic and right-thoracic AIS. In the vestibular analysis, geometric morphological difference was detected on the left-side semicircular canals between right-thoracic AIS and healthy controls. These morphological changes are likely to be related to the subclinical postural, vestibular, and proprioceptive dysfunctions. Further association studies and longitudinal studies could help to further define the link between morphological and functional dysfunction, which might have important predictive and prognostic effect on curve development and progression

Osteophyte deposition and subchondral bone damage are notable features of osteoarthritis (OA). Deregulated mineralization contributes to osteophyte and subchondral irregularity. The microRNA-29 (miR-29) family is associated with arthritic disorders. This study is aimed to investigate miR-29a function to OA osteophyte formation and subchondral integrity. Intact and damaged articular cartilage in patients with end-stage knee OA who required total knee arthroplasty were harvested to probe miR-29a, cartilage, and mineralized matrix expression using RT-PCR and in situ hybridization. Osteophyte volume and subchondral morphometry of collagenase-induced OA knees in mice were quantified using μCT and histomorphometry. Increased bone matrix expression (collagen I and bone alkaline phosphatase) and reduced cartilage matrix (collagen II and aggrecan) along with low miR-29a expression existed in human OA specimens. Aged miR-29a knockout mice showed spontaneous osteophyte formation and articular cartilage erosion. In primary articular chondrocytes, miR-29a deficiency significantly reduced cartilage matrix synthesis, whereas von Kossa staining-positive mineralized matrix production was increased. Of interest, the severity of collagenase-induced osteophyte accumulation and subchondral damage along with serum cartilage breakdown products CTX-II and COMP levels were significantly compromised in mice overexpressing miR-29a. Intra-articularly injecting miR-29a significantly reduced osteophyte volume and subchondral integrity and retained cartilage morphology in collagenase-injured knees. Reduced miR-29a signalling worsens osteophyte and subchondral destruction in OA through increasing mineralized matrix formation of chondrocytes. Restoring miR-29a shields joints from cartilage degradation, osteophyte and subchondral destruction. This study conveys new mechanistic underlying OA osteophyte pathogenesis and shines light on the remedial potential of miR-29a to OA