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The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1363 - 1368
1 Dec 2024
Chen DB Wood JA Griffiths-Jones W Bellemans J Haddad FS MacDessi SJ

As advancements in total knee arthroplasty progress at an exciting pace, two areas are of special interest, as they directly impact implant design and surgical decision making. Knee morphometry considers the three-dimensional shape of the articulating surfaces within the knee joint, and knee phenotyping provides the ability to categorize alignment into practical groupings that can be used in both clinical and research settings. This annotation discusses the details of these concepts, and the ways in which they are helping us better understand the individual subtleties of each patient’s knee. Cite this article: Bone Joint J 2024;106-B(12):1363–1368


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Methods

The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Methods

HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 7 - 7
11 Apr 2023
Hart M Selig M Azizi S Walz K Lauer J Rolauffs B
Full Access

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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 48 - 48
1 Nov 2021
Bundkirchen K Ye W Xu B Krettek C Relja B Neunaber C
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 43 - 43
1 Nov 2021
Peiffer M Arne B Sophie DM Thibault H Kris B Jan V Audenaert E
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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


Bone & Joint Research
Vol. 10, Issue 8 | Pages 514 - 525
2 Aug 2021
Chen C Kang L Chang L Cheng T Lin S Wu S Lin Y Chuang S Lee T Chang J Ho M

Aims

Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.

Methods

Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 120 - 120
1 Mar 2021
Grammens J Peeters W Van Haver A Verdonk P
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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


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 58 - 58
1 Mar 2021
Chen Y Lian W Wang F
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 59 - 59
1 Jul 2020
Chim Y Cheung W Chow SK
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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


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 81 - 81
1 Jul 2020
Wang F Sun Y Ke H
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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


Bone & Joint Research
Vol. 9, Issue 7 | Pages 368 - 385
1 Jul 2020
Chow SK Chim Y Wang J Wong RM Choy VM Cheung W

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.


The Bone & Joint Journal
Vol. 102-B, Issue 6 | Pages 749 - 754
1 Jun 2020
Jung H Park MJ Won Y Lee GY Kim S Lee JS

Aims

The aim of this study was to analyze the association between the shape of the distal radius sigmoid notch and triangular fibrocartilage complex (TFCC) foveal tear.

Methods

Between 2013 and 2018, patients were retrospectively recruited in two different groups. The patient group comprised individuals who underwent arthroscopic transosseous TFCC foveal repair for foveal tear of the wrist. The control group comprised individuals presenting with various diseases around wrist not affecting the TFCC. The study recruited 176 patients (58 patients, 118 controls). The sigmoid notch shape was classified into four types (flat-face, C-, S-, and ski-slope types) and three radiological parameters related to the sigmoid notch (namely, the radius curvature, depth, and version angle) were measured. The association of radiological parameters and sigmoid notch types with the TFCC foveal tear was investigated in univariate and multivariate analyses. Receiver operating characteristic curves were used to estimate a cut-off for any statistically significant variables.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_13 | Pages 11 - 11
1 Nov 2019
Mittal S Kumar A Trikha V
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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


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 116 - 116
1 Nov 2018
Sun YC Lian WS Ko JY Wang FS
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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


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 86 - 86
1 Apr 2018
Geurts J Burckhardt D Netzer C Schären S
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Introduction. Histology remains the gold standard in morphometric and pathological analyses of osteochondral tissues in human and experimental bone and joint disease. However, histological tissue processing is laborious, destructive and only provides a two-dimensional image in a single anatomical plane. Micro computed tomography (μCT) enables non-destructive three-dimensional visualization and morphometry of mineralized tissues and, with the aid of contrast agents, soft tissues. In this study, we evaluated phosphotungstic acid-enhanced (PTA) μCT to visualize joint pathology in spine osteoarthritis. Methods. Lumbar facet joint specimens were acquired from six patients (5 female, age range 31–78) undergoing decompression surgery. Fresh osteochondral specimens were immediately fixed in formalin and scanned in a benchtop μCT scanner (65 kV, 153 mA, 25 μm resolution). Subsequently, samples were completely decalcified in 5% formic acid, equilibrated in 70% ethanol and stained up to ten days in 1% PTA (w/v) in 70% ethanol. PTA-stained specimens were scanned at 70 kV, 140 mA, 15 μm resolution. Depth-dependent analysis of X-ray attenuation in cartilage tissues was performed using ImageJ. Bone structural parameters of undecalcified and PTA-stained specimens were determined using CT Analyser and methods were compared using correlation and Bland-Altman analysis. Results. The maximal penetration depth of PTA in decalcified facet joint was 5 mm. Bone tissue showed strong and uniformly distributed X-ray attenuation, while mild to moderate and differentially distributed attenuation was observed in articular cartilage and subchondral marrow spaces. Measurements of bone volume (r=0.90, p=0.01) and bone surface (r=0.95, p=0.004) were strongly correlated between undecalcified and PTA-stained samples. Compared with PTA-stained samples, measurements in undecalcified specimens were consistently higher (∼14%). PTA-enhanced μCT visualization of cartilage tissues enabled the identification of individual chondrocytes and their pericellular microenvironment (chondrons). Owing to loss of collagen lower X-ray attenuation was observed in the middle and deep cartilage layers at the central, but not peripheral, regions of the degenerated facet joint specimens. Depth-dependent analysis of PTA-staining intensity suggested that the extent of collagen loss in articular cartilage might correlate with the thickness of the subchondral cortical plate. Conclusion. PTA-enhanced μCT is a low-cost, non-toxic and highly feasible method for ex vivo 3D-visualization of osteochondral pathology in human osteoarthritis. The method enables bone morphometric analysis, as well as collagen distribution in all anatomical planes. Contrast enhanced μCT has several applications in bone and osteoarthritis research including 3D histopathological grading, tissue stratification, and imaging and analysis of aberrant collagen metabolism in osteochondral disease


The Bone & Joint Journal
Vol. 99-B, Issue 7 | Pages 894 - 903
1 Jul 2017
Bonnin MP Saffarini M Nover L van der Maas J Haeberle C Hannink G Victor J

Aims. The morphometry of the distal femur was largely studied to improve bone-implant fit in total knee arthroplasty (TKA), but little is known about the asymmetry of the posterior condyles. This study aimed to investigate the dimensions of the posterior condyles and the influence of externally rotating the femoral component on potential prosthetic overhang or under-coverage. Patients and Methods. We analysed the shape of 110 arthritic knees at the time of primary TKA using pre-operative CT scans. The height and width of each condyle were measured at the posterior femoral cut in neutral position, and in 3º and 5º of external rotation, using both central and medial referencing systems. We compared the morphological characteristics with those of 14 TKA models. Results. In the neutral position, the dimensions of the condyles were nearly equal. Externally rotating the femoral cut by 3º and 5º with ‘central referencing’ induced width asymmetry >  3 mm in 23 (21%) and 33 (30%) knees respectively, while with ‘medial referencing’ it induced width asymmetry > 3 mm in 43 (39%) and 75 (68%) knees respectively. The asymmetries induced by rotations were not associated with gender, aetiology or varus-valgus alignment. Conclusion. External rotation may amplify the asymmetry between the medial and lateral condyles, and exacerbate prosthetic overhang, particularly in the superolateral zone. ‘Central referencing’ guides result in less potential prosthetic overhang than ‘medial referencing’ guides. Cite this article: Bone Joint J 2017;99-B:894–903


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 30 - 30
1 Jan 2017
Pazzaglia U Congiu T Sibilia V Pagani F Benetti A Zarattini G
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The study of the chondrocyte maturation cycle and endochondral ossification showed that the developing vascular supply has appeared to play a key role in determining the cortical or trabecular structure of the long bones. The chondrocyte maturation cycle and endochondral ossification were studied in human, foetal cartilage anlagen and in postnatal meta-epiphyses. The relationship between the lacunar area, the inter territorial fibril network variations and CaP nucleation in primary and secondary ossification centres were assessed using light microscopy and SEM morphometry. The anlage topographic, zonal classification derived from the anatomical nomenclature of the completely developed long bone (diaphysis, metaphyses and epiphyses) allowed to follow the development of long bones cartilage model. A significant increase in chondrocyte lacunar area (p<0.001) was documented from the anlage epiphyseal zone 4 and 3 to zone 2 (metaphysis) and zone 1 (diaphysis), with the highest variation from zone 2 to zone 1. An inverse reduction in the intercellular matrix area (p<0.001) and matrix interfibrillar empty space (p<0.001) was also documented. These findings are consistent with the osmotic passage of free cartilage water from the interfibrillar space into the swelling chondrocytes, raising ion concentrations up to the critical threshold for mineral precipitation in the matrix. The mineralised cartilage served as a scaffold for osteoblasts apposition both in primary and secondary ossification centres and in the metaphyseal growth plate cartilage, but at different periods of bone anlage development and with distinct patterns for each zone. They all shared a common initial pathway, but it progressed with different times, modes and organisation in diaphysis, metaphysis and epiphysis. In the ossification phase the developing vascular supply has appeared to play a key role in determining the cortical or trabecular structure of the long bones


Bone & Joint Research
Vol. 5, Issue 6 | Pages 253 - 262
1 Jun 2016
Liu H Li W Liu YS Zhou YS

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


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_4 | Pages 37 - 37
1 Jan 2016
Stevens A Surabhi R Jaarsma R Bramwell D Krishnan J
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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