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The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 613 - 622
1 Jun 2024
Shen J Wei Z Wu H Wang X Wang S Wang G Luo F Xie Z

Aims

The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

Methods

Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 350 - 360
23 Apr 2024
Wang S Chen Z Wang K Li H Qu H Mou H Lin N Ye Z

Aims

Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS.

Methods

A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 124 - 126
11 Mar 2024
Shen J Wei Z Sun D Wu H Wang X Wang S Luo F Xie Z

Cite this article: Bone Joint Res 2024;13(3):124–126.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 19 - 27
1 Jan 2024
Tang H Guo S Ma Z Wang S Zhou Y

Aims

The aim of this study was to evaluate the reliability and validity of a patient-specific algorithm which we developed for predicting changes in sagittal pelvic tilt after total hip arthroplasty (THA).

Methods

This retrospective study included 143 patients who underwent 171 THAs between April 2019 and October 2020 and had full-body lateral radiographs preoperatively and at one year postoperatively. We measured the pelvic incidence (PI), the sagittal vertical axis (SVA), pelvic tilt, sacral slope (SS), lumbar lordosis (LL), and thoracic kyphosis to classify patients into types A, B1, B2, B3, and C. The change of pelvic tilt was predicted according to the normal range of SVA (0 mm to 50 mm) for types A, B1, B2, and B3, and based on the absolute value of one-third of the PI-LL mismatch for type C patients. The reliability of the classification of the patients and the prediction of the change of pelvic tilt were assessed using kappa values and intraclass correlation coefficients (ICCs), respectively. Validity was assessed using the overall mean error and mean absolute error (MAE) for the prediction of the change of pelvic tilt.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 546 - 558
12 Sep 2023
Shen J Wei Z Wang S Wang X Lin W Liu L Wang G

Aims

This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes.

Methods

A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims

Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.

Methods

In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage.


Bone & Joint Open
Vol. 3, Issue 3 | Pages 211 - 217
1 Mar 2022
Hsu C Chen C Wang S Huang J Tong K Huang K

Aims

The Coronal Plane Alignment of the Knee (CPAK) classification is a simple and comprehensive system for predicting pre-arthritic knee alignment. However, when the CPAK classification is applied in the Asian population, which is characterized by more varus and wider distribution in lower limb alignment, modifications in the boundaries of arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) should be considered. The purposes of this study were as follows: first, to propose a modified CPAK classification based on the actual joint line obliquity (aJLO) and wider range of aHKA in the Asian population; second, to test this classification in a cohort of Asians with healthy knees; third, to propose individualized alignment targets for different CPAK types in kinematically aligned (KA) total knee arthroplasty (TKA).

Methods

The CPAK classification was modified by changing the neutral boundaries of aHKA to 0° ± 3° and using aJLO as a new variable. Radiological analysis of 214 healthy knees in 214 Asian individuals was used to assess the distribution and mean value of alignment angles of each phenotype among different classifications based on the coronal plane. Individualized alignment targets were set according to the mean lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) of different knee types.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 401 - 410
13 Jul 2021
Liu Z Wang H Wang S Gao J Niu L

Aims

Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Methods

The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 10, Issue 7 | Pages 380 - 387
5 Jul 2021
Shen J Sun D Fu J Wang S Wang X Xie Z

Aims

In contrast to operations performed for other fractures, there is a high incidence rate of surgical site infection (SSI) post-open reduction and internal fixation (ORIF) done for tibial plateau fractures (TPFs). This study investigates the effect of induced membrane technique combined with internal fixation for managing SSI in TPF patients who underwent ORIF.

Methods

From April 2013 to May 2017, 46 consecutive patients with SSI post-ORIF for TPFs were managed in our centre with an induced membrane technique. Of these, 35 patients were included for this study, with data analyzed in a retrospective manner.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_9 | Pages 2 - 2
1 Jun 2021
Tang H Wang S Zhou Y Li Y Zhao Y Shi H
Full Access

Introduction

The functional ante-inclination (AI) of the cup after total hip arthroplasty (THA) is a key component in the combined sagittal index (CSI) to predict joint stability after THA. To accurately predict AI, we deducted a mathematic algorithm between the radiographic anteversion (RA), radiographic inclincation (RI), pelvic tilting (PT), and AI. The current study aims (1) to validate the mathematic algorithm; (2) to convert the AI limits in the CSI index (standing AI ≤ 45°, sitting AI ≥ 41°) into coronal functional safe zone (CFSZ) and explore the influences of the stand-to-sit pelvic motion (PM) and pelvic incidence (PI) on CFSZ; (3) to locate a universal cup orientation that always fulfill the AI criteria of CSI safe zone for all patients or subgroups of PM(PM ≤ 10°, 10° < PM ≤ 30°, and PM > 30°) and PI (PI≤ 41°, 41°< PI ≤ 62°, and PI >62°), respectively.

Methods

A 3D printed phantom pelvic model was designed to simulate changing PT values. An acetabular cup was implanted with different RA, RI, and PT settings using robot assisted technique. We enrolled 100 consecutive patients who underwent robot assisted THA from April, 2019 to June, 2019 in our hospital. EOS images before THA and at 6-month follow-up were collected. AI angles were measured on the lateral view radiographs as the reference method. Mean absolute error (MAE), Bland-Altman analysis and linear regression were conducted to assess the accuracy of the AI algorithm for both the phantom and patient radiographic studies. The 100 patients were classified into three subgroups by PM and PI, respectively. Linear regression and ANOVA analysis were conducted to explore the relationship between the size of CFSZ, and PM and PI, respectively. Intersection of the CFSZ was conducted to identify if any universal cup orientation (RA, RI) existed for the CSI index.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 328 - 339
31 May 2021
Jia X Huang G Wang S Long M Tang X Feng D Zhou Q

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods

In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.


Aims

Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones.

Methods

Between January 2013 and December 2017, 26 young patients with COM were enrolled. Different bone grafts were applied to repair bone defects secondary to IMT procedure for infection eradication. Group BMCA was administered BMCA while Group BMAA was given BMAA. The results of this case-control study were retrospectively analyzed.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_2 | Pages 105 - 105
1 Feb 2020
Friedrich C Wang S Francis A Baker E
Full Access

Prior work in the setting of MRSA (clinical isolate), showed that enhancement of Ti6Al4V with anodized nanotubes apparently disrupts the formation and adhesion of MRSA biofilm. The greater amount of cultured MRSA using effluent released from in vitro nanotube surfaces by sonication, compared with thermal plasma sprayed (TPS), indicated probable disruption of biofilm formation and adhesion. The use of nanosilver nanotubes in vivo in a rabbit model showed that after 1 week of infection followed by 1 week of vancomycin treatment, the nanotube MRSA level was 30% that of TPS, and the nanosilver nanotube MRSA level was only 5% of TPS. The implementation of the technology will enhance the remodeled bone locking ability of rough TPS, with surface nanotubes that provide antibacterial properties and increased bone adhesion.

Lap shear tests of the nanotubes were performed according to ASTM F1044. In multiple tests, circular adhesive films bonded Ti6Al4V bars containing nanotubes with plain Ti6Al4V. The assemblies were suitably arranged in a tensile tester and pulled to shear failure. There were three modes of failure; shear failure within the adhesive, failure of the adhesive from the plain titanium, and shear failure of the nanotubes from the bar. Tests determined the shear strength of the adhesive and its bonding strength to bare titanium. ImageJ software determined the area of each of the three failure modes. From this analysis, the shear strength of the nanotubes of each sample was calculated.

The analyses showed the shear strength of the nanotubes to be as high as 65MPa (9,500psi) with a more typical shear strength of 55MPa (8,000 psi), and several surfaces with 45MPa (6,000 psi). The literature presents models predicting the shear stress in bonded hip stems. Assuming the TPS with nanotubes performs similar to a bonded hip stem, owing to the locking of the bone with the TPS, a typical shear stress prediction for physiological loads is approximately 10 MPa. The nanotube shear strengths were 4–6 times higher than the expected stress during use.

For any figures or tables, please contact authors directly.


The Bone & Joint Journal
Vol. 102-B, Issue 2 | Pages 205 - 211
1 Feb 2020
Shao X Shi LL Bluman EM Wang S Xu X Chen X Wang J

Aims

To evaluate the donor site morbidity and tendon morphology after harvesting whole length, full-thickness peroneus longus tendon (PLT) proximal to the lateral malleolus for ligament reconstructions or tendon transfer.

Methods

A total of 21 eligible patients (mean age 34.0 years (standard deviation (SD) 11.2); mean follow-up period 31.8 months (SD 7.7), and 12 healthy controls (mean age, 26.8 years (SD 5.9) were included. For patients, clinical evaluation of the donor ankle was performed preoperatively and postoperatively. Square hop test, ankle strength assessment, and MRI of distal calf were assessed bilaterally in the final follow-up. The morphological symmetry of peroneal tendons bilaterally was evaluated by MRI in healthy controls.


The Bone & Joint Journal
Vol. 101-B, Issue 6 | Pages 695 - 701
1 Jun 2019
Yang H Wang S Lee K

Aims

The purpose of this study was to determine the functional outcome and implant survivorship of mobile-bearing total ankle arthroplasty (TAA) performed by a single surgeon.

Patients and Methods

We reviewed 205 consecutive patients (210 ankles) who had undergone mobile-bearing TAA (205 patients) for osteoarthritis of the ankle between January 2005 and December 2015. Their mean follow-up was 6.4 years (2.0 to 13.4). Functional outcome was assessed using the Ankle Osteoarthritis Scale, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, 36-Item Short-Form Health Survey (SF-36) score, visual analogue scale, and range of movement. Implant survivorship and complications were also evaluated.


Objectives

Previously, we reported the improved transfection efficiency of a plasmid DNA-chitosan (pDNA-CS) complex using a phosphorylatable nuclear localization signal-linked nucleic kinase substrate short peptide (pNNS) conjugated to chitosan (pNNS-CS). This study investigated the effects of pNNS-CS-mediated miR-140 and interleukin-1 receptor antagonist protein (IL-1Ra) gene transfection both in rabbit chondrocytes and a cartilage defect model.

Methods

The pBudCE4.1-miR-140, pBudCE4.1-IL-1Ra, and negative control pBudCE4.1 plasmids were constructed and combined with pNNS-CS to form pDNA/pNNS-CS complexes. These complexes were transfected into chondrocytes or injected into the knee joint cavity.


Bone strength is influenced by bone quality besides its density. This study aimed to evaluate the effects of teriparatide on changes of bone strength as well as trabecular and cortical bone microstructures at femoral neck in female ovariectomized (OVX) rats. Eighteen female Wister rats were divided into three groups: the sham control, OVX and treatment (Tx) groups. All of them were sacrificed after 3-month intermittent teriparatide intervention in Tx group. All left femurs were removed and scanned using micro-CT and followed by mechanical test for each femoral neck. Regarding micro-CT, four trabecular parameters including bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN) and three cortical parameters including volumetric bone mineral density (vBMD), cortical cross-sectional area (CtAr) and cortical thickness (CtTh) were measured at femoral neck region. All data were analyzed and was presented as median ± SEM. The mean bone strength of femoral neck significantly decreased in OVX group when compared to the control group (p < 0.05) and was significantly restored in Tx group (p < 0.01). Regarding the trabecular parameters, the BV/TV and TbTh significantly decreased in OVX group while compare to Tx group. However, no significant difference was observed in TbSp and TbN between the groups. Regarding the cortical parameters, CtTh was significantly greater in Tx group than that in OVX group (p<0.01). As our findings, intermittent teriparatide can improve the deteriorated bone strength of femoral neck due to ovarian deficiency via changing both trabecular microarchitecture and cortical morphology.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 494 - 500
1 Jul 2018
Jiang L Zhu X Rong J Xing B Wang S Liu A Chu M Huang G

Objectives

Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA.

Methods

We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 834 - 839
1 Jun 2016
Wang S Ma H Lin C Chou P Liu C Yu W Chang M

Aim

Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients.

Patients and Methods

Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit.


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 109 - 116
1 Jan 2016
Chou P Ma H Liu C Wang S Lee OK Chang M Yu W

Methods

In this study of patients who underwent internal fixation without fusion for a burst thoracolumbar or lumbar fracture, we compared the serial changes in the injured disc height (DH), and the fractured vertebral body height (VBH) and kyphotic angle between patients in whom the implants were removed and those in whom they were not. Radiological parameters such as injured DH, fractured VBH and kyphotic angle were measured. Functional outcomes were evaluated using the Greenough low back outcome scale and a VAS scale for pain.

Results

Between June 1996 and May 2012, 69 patients were analysed retrospectively; 47 were included in the implant removal group and 22 in the implant retention group. After a mean follow-up of 66 months (48 to 107), eight patients (36.3%) in the implant retention group had screw breakage. There was no screw breakage in the implant removal group. All radiological and functional outcomes were similar between these two groups. Although solid union of the fractured vertebrae was achieved, the kyphotic angle and the anterior third of the injured DH changed significantly with time (p < 0.05).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 2 - 2
1 Sep 2012
Li R Qamirani E Atesok K Nauth A Wang S Li C Schemitsch EH
Full Access

Purpose

Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. VEGF has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological and microCT evaluations (Atesok, Li, Schemitsch 2010); EPC treatment of fractures resulted in a significantly higher strength by biomechanical examination (Li, Schemitsch 2010). In addition, cell-based VEGF gene transfer has been effective in the treatment of segmental bone defects in a rabbit model (Li, Schemitsch et al 2009); Purpose of this study: Evaluation of VEGF gene expression after EPC local therapy for a rat segmental bone defect.

Method

Rat bone marrow-derived EPCs were isolated from the rat bone marrow by the Ficoll-paque gradient centrifuge technique. The EPCs were cultured for 7 to 10 days in endothelial cell growth medium with supplements (EGM-2-MV-SingleQuots, Clonetics). and collected for treatment of the rat segmental bone defect. EPCs were identified by immunocytochemistry staining with primary antibodies for CD34, CD133, FLK-1, and vWF. A total of fifty six rats were studied. A five millimeter segmental bone defect was created in the middle 1/3 of each femur followed by mini plate fixation. The treatment group received 1×106 EPCs locally at the bone defect and control animals received saline only. Seven control and seven EPC treated rats were included in each group at 1, 2, 3 and 10 weeks. Animals were sacrificed at the end of the treatment period, and specimens from the fracture gap area were collected and immediately frozen. Rat VEGF mRNA was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by VisionWorksLS. All measurements were performed in triplicate.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 186 - 186
1 May 2011
Chong M Broome G Wang S
Full Access

Background: Prior studies identified that crash severity (Delta V), occupant position, and restraint systems as reliable predictors of crash injuries.1–5 Others have noted that correlation between the biomedical thresholds (age, gender, height, weight) and injury pattern to the lower extremity but very little have been written on the subject of upper extremity.

METHOD: This is a retrospective analysis of CIREN database in a level trauma center focusing on upper extremity injuries. The aim was to investigate the relationship between of the ‘crash’ and ‘occupant’ factors on the pattern and severity of upper extremity injuries following a frontal impact collision. results &

Discussion:Majority of the injuries were soft tissues type. (67.6% soft tissue vs. 32.4% fractures). There were 144 fractures to the upper extremity, 12.5% were ‘open’ fractures. 66% of cases of fractures required operative intervention. 74.5% of the fractures sustained in the upper extremity occurred distal to the elbow, whereas soft tissue injuries predominated in the humerus. 21.5% of distal radius fractures were attributed to airbag deployment and all of the clavicle fractures were related to compression from seat belt. Occupants who sustained fractures had a significantly higher ISS scores (mean score 21.88 vs. 17.68, p < 0.05). Using logistic binary regression model, the ISS continued to be a significant predictor for fracture, overriding weight as a co-founding variable. Of the 144 fractures, 66% of cases required operative intervention.

Conclusion:. To advance occupant protection, it is important to understand the differences in individual variability in affecting injury tolerance in high-energy trauma. One could argue that current modern restraint systems are not designed to protect these vulnerable areas; therefore it may not come as a surprise to observe such an emerging trend of injuries to the upper extremities. There is no doubt that modern restraint systems have contributed to the overall decrease in mortality over the years. However, there are case series reported on the effect of airbag-related injuries to upper extremities as a consequence of its primary effectiveness. Our study reinforce the debate for a more ‘depowered’ airbag capable of saving lives yet simultaneously protecting the upper extremities from serious injuries.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 442 - 443
1 Aug 2008
Moreau A Boulanger H Aubin C Mathieu P Wang S Bagnall K
Full Access

Introduction: Over the last three years, we have demonstrated the complex role of melatonin, a hormone produces mainly in the brain, in the development of scoliosis and in particular by reporting for the first time that cells from AIS patients cannot respond to melatonin, which contrasted with similar cells isolated from healthy subjects. We have determined that this phenomenon is caused by chemical modifications affecting the activity of Gi proteins, a group of small proteins normally associated with both melatonin receptors. Interestingly, previous studies showed that melatonin deficiency could also induce a scoliosis suggesting that the asymmetrical growth of the spine in humans and in melatonin deficient animals could be caused by a common downstream effector regulated by melatonin. This study was then designed to determine and characterise the early biochemical, cellular and molecular changes underlying the formation of spinal deformities in growing pinealectomized chicken and in bipedal C57Bl/6 mice, a naturally melatonin deficient strain of mice.

Methods: For this study, 145 newly hatched chickens (Mountain Hubbard) were purchased at a local hatchery and divided into three distinct groups. First group, pinealectomized (n=100), underwent complete removal of the pineal gland. The second group, sham (n=20), underwent superficial cranial incision without the ablation of the pineal gland. The third group, control (n=25), the chickens did not undergo any surgical procedure. All surgeries were performed by the same surgeon between day three and five after hatching. At days 14, 21 and 28 chicken underwent radiographic examination with a DEXA bone densitometer (PIXImus II, Lunar Corp., Madison, WI). Each digital image was evaluated for the presence of scoliosis and the degree of curvature was measured. Cobb angle threshold value of 10° and higher was retained as a significant scoliotic condition. Blood samples (1 to 2 ml) were taken from a peripheral wing vein of each chicken (from 6 am to 9 am) at the age of 14, 21 and 28 days. Sera were collected by centrifugation and immediately stored at −80°C until assayed. Serum melatonin concentrations were determined using an ELISA method (IBL, Hamburg, Germany). At day 28, chicken were euthanised and tissues were collected to extract mRNA for expression analysis or proteins for subsequent detection. C57Bl/6 mice (n=50) were purchased from Charles-Rivers and bipedal mice were generated by removing the forelimbs and tail after weaning (three weeks old) according to a protocol approved by our institutional animal health care committee. Sera of AIS patients and matched healthy controls were also analysed to determine the levels of circulating P factor using an ELISA assay.

Results: Our results demonstrated a more dynamic variation of circulating melatonin level only in pinealectomised chicken developing a scoliosis, which allowed us to separate scoliotic chicken in two distinct groups. In the first group, the animals showed a biphasic response with a strong decrease of melatonin level between days 14 to 21, followed by a rapid recovery to almost reach the normal values at day 28. In the second group, pinealectomised chickens showed a linear decrease of circulating melatonin over the three-week period while, non-scoliotic pinealectomised chicken showed non-significant variations in melatonin concentration with values close to those obtained with the shams. At the molecular level, expression analysis demonstrated higher expression of a gene encoding a protein that has been termed P factor only in paraspinal muscles of pinealectomized chicken developing a scoliosis. Accumulation of P factor was also confirmed at the protein level by Western blot analysis. Bipedal C57Bl/6 mice, which are naturally melatonin deficient, developed also scoliotic deformities in a proportion of 45% over a two-month period. Interestingly, we observed that genetically modified mice devoid of P factor (n=60) or one of its receptor (n=40) in the same genomic background (C57Bl/6) cannot develop a scoliosis in the same conditions. Moreover, P factor circulating levels in scoliotic patients showed a 2–4 fold increase when compared to healthy matched individuals.

Conclusions: These results showed for the first time a more dynamic variation in circulating melatonin levels among pinealectomised chicken, which was unsuspected by previous studies. Interestingly, a transient decrease of circulating melatonin level was sufficient to induce scoliotic deformities during the first two weeks even if melatonin concentration was subsequently recovered a week later. This may explain why melatonin injection in pinealectomised chicken is not always efficient in preventing scoliosis. Taken together, these observations further suggest that a melatonin decrease below a certain threshold during a specific postnatal window may be sufficient to trigger a scoliosis and reconcile the data concerning AIS patients showing in most of the studies no significant variation when analysed at late stages. The study of early molecular changes in animal models also led us to identify a novel factor, which appears essential to initiate scoliosis through a specific signalling action. The clinical relevance of the P factor in AIS and related spinal syndromes is further strengthened by the detection of high levels of P factor only in scoliotic patients and could pave the way for the development of innovative diagnosis tools as well as the first pharmacological treatments to prevent scoliosis deformities in children.

Research project supported by La Fondation Yves Cotrel de l’Institut de France


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 153 - 154
1 Feb 2003
Cannon L Wang S
Full Access

The aim of this study was to analyse compressive injuries to the lower limb with data obtained from crash reconstruction to examine injury mechanics (IM’s) and aid car safety.

Prospectively gathered injury and crash reconstruction data were examined from drivers sustaining femoral and/or acetabular fractures (including hip dislocations) following frontal collisions. There were 23 femoral fractures, 21 acetabular and 4 patients with combined femoral and acetabular fractures. It was hypothesised that different IM’s accounted for the relative exclusivity in injury distribution.

There were no statistically significant differences between the two groups with regards to age, weight, height, injury severity scores (ISS) and the relative velocity of impact (mean of 32 and 26mph for femoral and acetabular fractures respectively). Damage to the knee bolster on the side of injury was evident in 21 femoral fractures (1 car burnt out) and 18 acetabular (1 car burnt out). Females were more likely to sustain a femoral fracture than males (71% versus 45%).

Femoral and acetabular fractures do appear to be the result of compressive loadings to the femur as evident by damage to the knee bolsters. Both fracture types arise from low velocity impacts but the IM’s appear different. The driving position of females or their anthropomorphic differences may account for their higher propensity for femoral injury. The deployment of an airbag while not wearing a seatbelt may cause the occupant to ‘submarine’ beneath the airbag. Subsequent impact of the knee against the bolster may impart different energy loading characteristics to the femur to that of belted occupants. Knee bolster design may thus be of importance in injury modification. Assuming that acetabular fractures are associated with greater morbidity than femoral fractures, these data further support the advice that seatbelts be worn.