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Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Methods

Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 103 or 1 × 106 colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 103 or 1 × 106 CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


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.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Methods

CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 13 - 13
7 Nov 2023
Salence B Kruger N
Full Access

A retrospective follow-up study was done, assessing regional practices in acute cervical reduction in hospitals in the Western Cape. The constitutional court ruled on the urgency in managing cervical dislocations, and our task is to ensure that medical treatment is optimized to comply with best medical practice and the apex court. A questionnaire was distributed and completed by emergency departments at each hospital, the results retrieved, analysed, and compared to a similar survey done in 2016. Protocols for managing cervical spine dislocations had improved from 80% having no protocols to only over half of facilities (52,6%) not having protocols in place. Inadequate equipment availability remained a problem with only 50% of facilities having adequate equipment available in 2016 to 43,6% in 2023. 10,3% of participants did not know if there was equipment available. In terms of knowledge, there remained poor formal training with a drop from 93% participants identifying that the main indication to attempt emergency cervical reduction was acute cervical dislocation with worsening neurology, to only 46,2%. However, there was an increase in the number of participants who thought reduction was safe. The same percentage of participants from 2016 to 2023 would attempt emergency cervical reduction if given adequate training. Previously we found that most Western Cape hospitals had inadequate protocols, training, and equipment for cervical reductions. In 2023, more hospitals in the Province have protocols in place for cervical reductions and the same percentage of doctors would attempt emergency cervical reduction with adequate training. However, equipment and training for management of acute cervical dislocations has not improved. We conclude that most Western Cape Hospitals are unprepared to adequately manage acute cervical dislocations


Bone & Joint Research
Vol. 12, Issue 10 | Pages 657 - 666
17 Oct 2023
Sung J Barratt KR Pederson SM Chenu C Reichert I Atkins GJ Anderson PH Smitham PJ

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Methods

Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq).


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Methods

Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 659 - 667
1 Oct 2021
Osagie-Clouard L Meeson R Sanghani-Kerai A Bostrom M Briggs T Blunn G

Aims

A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing.

Methods

A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis.


Bone & Joint Open
Vol. 1, Issue 9 | Pages 512 - 519
1 Sep 2020
Monzem S Ballester RY Javaheri B Poulet B Sônego DA Pitsillides AA Souza RL

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Methods

Three groups (seven per group) of 12-week-old mice were: 1) ovariectomized and 20 weeks thereafter treated weekly for 24 weeks with 100 μm/kg subcutaneous ibandronate (OVX+IBN); 2) ovariectomized (OVX); or 3) sham-operated (SHAM). Quantitative fracture analysis generated biomechanical properties for the femoral neck. Tibiae were microCT scanned and trabecular (proximal metaphysis) and cortical parameters along almost its whole length measured.


Bone & Joint Research
Vol. 7, Issue 12 | Pages 620 - 628
1 Dec 2018
Tätting L Sandberg O Bernhardsson M Ernerudh J Aspenberg† P

Objectives

Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline.

Methods

Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_13 | Pages 29 - 29
1 Sep 2014
Mughal A Kruger N
Full Access

Cervical bifacet dislocations are devastating injuries and require early reduction and surgical stabilization. Closed reduction is safe and neurological deterioration is rare. Pre-reduction MRI can cause clinical uncertainty as to the safety of closed reduction when a significant sequestrated disc is found. This study explores the direct cord pressures in a bifacet dislocation model with the use of fresh frozen cadaver cervical spines and a Tekscan Pressure Measurement System. Method. Surgical dislocations were created and pressure monitors inserted into the canal. Pressures on the cord from the posterior-superior edge of the caudal body as well as that from the cranial body were assessed at the level of the dislocation. The effects of the presence of a disc and its size, reduction angles and level of dislocation before and during closed reduction were evaluated. Results. The average dislocated spinal cord pressures were measured at 3.81 kPa and increased to 20.22 kPa under traction. This decreased to 1.295 kPa after cervical spine reduction. Average cord pressures as well as peak loading pressures were shown to increase with the increasing size of the prolapsed disc and diminished once the spine was reduced. Conclusion. This model provides additional insight into cervical spine dislocation and the contribution of disc prolapse to cord injury. NO DISCLOSURES


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 12 | Pages 1646 - 1652
1 Dec 2011
Newton D England M Doll H Gardner BP

The most common injury in rugby resulting in spinal cord injury (SCI) is cervical facet dislocation. We report on the outcome of a series of 57 patients with acute SCI and facet dislocation sustained when playing rugby and treated by reduction between 1988 and 2000 in Conradie Hospital, Cape Town. A total of 32 patients were completely paralysed at the time of reduction. Of these 32, eight were reduced within four hours of injury and five of them made a full recovery. Of the remaining 24 who were reduced after four hours of injury, none made a full recovery and only one made a partial recovery that was useful. Our results suggest that low-velocity trauma causing SCI, such as might occur in a rugby accident, presents an opportunity for secondary prevention of permanent SCI. In these cases the permanent damage appears to result from secondary injury, rather than primary mechanical spinal cord damage. In common with other central nervous system injuries where ischaemia determines the outcome, the time from injury to reduction, and hence reperfusion, is probably important.

In order to prevent permanent neurological damage after rugby injuries, cervical facet dislocations should probably be reduced within four hours of injury.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 251 - 251
1 Jul 2011
Zhu Q Liu J Bhatnagar T Tetzlaff W Oxland T
Full Access

Purpose: Recent studies have shown differences in short term spinal cord pathology between spinal column injury mechanisms, such as contusion and fracture-dislocation. Such differences may exist at longer time points, and thus survival studies are needed in the dislocation models. A more in-depth characterization of the dislocation model is needed for development of a mild-moderate cervical spine dislocation model in a rat that is suitable for survival studies. Specifically, our objective in this study was to determine the dislocation displacement that produces initial spinal column failure in a Sprague-Dawley rat model and to validate a consistent injury at the desired dislocation in-vitro and in-vivo. Method: For the dislocation model, the dorsal ligaments and facets at C4–C5 were removed to mimic the type of posterior element fracture and ligament injury commonly seen in a bilateral fracture-dislocation. C3 and C4 were clamped together and held stationary while the clamp holding C5 and C6 was connected to an electromagnetic actuator and displaced dorsally to produce the injury while force and displacement were recorded. Twenty-eight isolated cervical spine specimens of Sprague-Dawley rats were used to determine dislocation displacement at initial spinal column failure. The C4–C5 segment sustained dislocation (> 3mm) injury at 0.05mm/s (n=11), 100mm/s (n=4) and 1000mm/s (n=13). Initial spinal column failure was defined at with maximum force during the dislocation. A dislocation displacement of 1.4mm was applied to 7 isolated specimens and 4 anesthetized rats at 430mm/s. The spinal column failure was inspected up to 3 days after injury, as well as hemorrhage of spinal cord in-situ. Results: The dislocation displacement at in-vitro spinal column failure was 0.95mm±0.32 and not significantly different among specimens at the three dislocation speeds. Under a dislocation displacement of 1.4mm, rupture of the C4–C5 disc occurred in all in-vitro (0.67mm±0.38) and in-vivo (0.65mm±0.17) cases. SCI hemorrhage at epicenter was observed in 3 of 4 cases. Conclusion: The initial spinal column failure in an innovative SCI model occurs at displacement between 0.65mm and 0.95mm. Dislocation displacement of 1.4mm results in spinal column failure consistently and SCI hemorrhage, and may be suitable for survival studies


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 116 - 120
1 Jan 2007
Laing AJ Dillon JP Condon E Coffey JC Street JT Wang JH McGuinness AJ Redmond HP

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.

Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1+) and stem cell factor receptor, CD117 (c-kit+) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1+ mononuclear cell (MNCsca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNCsca-1+,c-kit+ counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.

Sca-1+ mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.

Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 290 - 290
1 Sep 2005
Lukhele M
Full Access

Introduction and Aims: The management of cervical spine dislocation is a challenge and can be a topic of big debate. Delay diagnosis of these injuries presents a bigger challenge. The aim of this study is to review patients who presented and were managed after four weeks from the time of injury. Method: A retrospective study of 15 patients with unifacet and bifacet dislocation referred to the author four weeks after the injury between 1990 and 2003 were reviewed. Their clinical records and x-rays on admission and up to final discharge from follow-up were studied. Some patients were interviewed by telephone and a recent x-ray was requested. The following factors were assessed: age, mechanism of injury, delay period from the time of injury when referred, clinical picture at presentation, treatment given and clinical picture at final discharge or interview. Results: The age range at presentation was 24 to 56 years. The delay period to presentation and management by the author was six weeks to three years. At presentation all had neck pain, three had upper limb paraesthesia, six had radiculopathy, four had Frankel D myelopathy and two were neurologically intact. Eleven patients had involvement of C5/6, three had C4/5 and one had C6/7 involvement. Seven patients had been treated by the primary medical team with traction, five with a soft collar for a few weeks, two had no treatment and one was a re-injury. Skeletal traction was applied to all patients on admission. Only three patients were successfully reduced with the prolonged traction; they were further managed by anterior discectomy, fusion and anterior cervical spine plating. The remaining patients were treated by corpectomy of the caudal vertebrae, strut graft and anterior cervical spine plating. None of the patients had posterior surgery. Fusion was achieved in all the patients. Cervical lordosis was restored in 10 of the 12 patients who underwent corpectomy, strut graft and plating. Motor power improved in all but two patients, who had radiculopathy. None of the patients had deterioration of neurology or neck pain at final follow-up. Conclusion: Anterior corpectomy of the caudal vertebrae, strut graft and cervical spine plating obtained good cervical lordosis and neurological improvement in patients with late presentation of cervical spine dislocation, which did not reduce with initial skeletal traction. This approach is less challenging than those advocated by previous authors exposed to managing these injuries


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 3 | Pages 352 - 356
1 May 1994
Lee A MacLean J Newton D

There is still some controversy about the reduction of unilateral and bilateral facet dislocations in the cervical spine. We have reviewed the notes and radiographs of 210 such patients; reduction was attempted by manipulation under anaesthesia (MUA) in 91, and by rapid traction under sedation in 119, using weights up to 150 lb (68 kg). Our results suggest that early reduction in patients with neurological deficit gives the best chance of neurological recovery, that rapid traction is more often successful than MUA, and that traction is safer than MUA. We found that the use of heavy weights with close monitoring was safe and brought about reduction in an average time of 21 minutes. We recommend this technique for the reduction of all cervical facet dislocations.


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 3 | Pages 403 - 409
1 May 1993
Mahale Y Silver Henderson N

We have studied the case records of 16 patients with dislocations of the cervical spine who deteriorated neurologically during or after reduction. The dislocations were reduced by skull traction in four patients, by manipulation in four and by operation in seven. This complication was not related to age, sex, mechanism of injury, or the level and the type of dislocation. Fourteen patients made substantial recoveries, one made a partial recovery and one patient remained totally paralysed and died three months later. The causes and prevention of spinal-cord damage at this stage of management are discussed, and the early use of MRI or CT myelography is recommended.


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 2 | Pages 224 - 227
1 Mar 1992
Robertson P Ryan M

We report three patients with neurological deterioration after the reduction of cervical spine dislocation. In each case compression of the spinal cord by disc material was demonstrated by magnetic resonance imaging and recovery occurred following removal of the compressing disc. A separate radiological study suggested that disproportionate narrowing of the disc space implies disc extrusion; reduction of a dislocation showing this sign may produce or exacerbate neurological deterioration


The Journal of Bone & Joint Surgery British Volume
Vol. 72-B, Issue 4 | Pages 679 - 681
1 Jul 1990
Louw J Mafoyane N Small B Neser C

We studied 12 consecutive patients with facet joint dislocation in the cervical spine to assess the incidence, site and clinical sequelae of occlusion of the extracranial vertebral artery. Intra-arterial digital subtraction angiography was performed after the orthopaedic management of the dislocations. This demonstrated vertebral artery occlusion (one bilateral) in five of the seven patients with bilateral dislocations and in four of the five patients with unilateral dislocations. Two of the nine patients with vertebral artery occlusion had neurological deficits above the level of the injury, all of which resolved spontaneously within two months. In our experience, a distraction-flexion injury appears to be the most common cause of closed traumatic vertebral artery occlusion.


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 2 | Pages 275 - 282
1 Mar 1989
Ostl O Fraser R Griffiths E

We compared retrospectively consecutive series of patients with cervical dislocation treated at two Australian centres. In Perth, 82 patients were treated by closed reduction and postural nursing. In Adelaide, 85 patients had closed reduction and early surgical stabilisation by interbody fusion. There were 46 bilateral dislocations, 101 unilateral dislocations, and 20 anterior subluxations. On admission 30 patients had complete tetraplegia, 17 incomplete tetraplegia, and 120 had minimal or no neurological loss. Our results indicated that closed manipulation under general anaesthesia is a safe and effective means of reduction in the acute stage. There was a high mortality rate for acute surgery in patients with complete tetraplegia. Early surgical stabilisation by dowel fusion reduced bed and hospital stay in patients with no neurological loss, but seemed to impair neurological recovery in patients with a neurological deficit on admission. Conservative management after reduction of bilateral dislocation or anterior subluxation led to a higher incidence of instability in patients with minimal or no neurological loss; in such cases surgery to stabilise the injured segment is indicated