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Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 65 - 65
1 Sep 2012
Carstens A Adam C Izatt M Labrom R Askin G
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The relationship between radiologic union and clinical outcome in thoracoscopic scoliosis surgery is not clear, as apparent non-union does not always correspond to a poor clinical result. Our aim was to evaluate CT fusion rates 2yrs after thoracoscopic surgery, and explore the relationship between fusion scores and; (i) rod diameter, (ii) graft type, (iii) fusion level, (iv) implant failure, and (v) lateral position in disc space.

Between 2000 and 2006 a cohort of 44 patients had thoracoscopic scoliosis correction. Discectomies were performed and defect was packed with either autograft (n=14) or allograft (n=30). Instrumentation consisted of either 4.5mm (n=24) or 5.5mm (n=20) single titanium anterior rod and vertebral body screws. Fusion quality and implant integrity were evaluated 2yr following surgery using low-dose CT. At each disc space, left, right and mid-sagittal CT reconstructions were generated and graded using the Sucato 4-point scale (Sucato, 2004) which is based on calculated percentage of fusion across disc space.

Fusion scores were measured for 259 disc spaces in 44 patients. Rod diameter had a strong effect on fusion score, with a mean score of 2.12±0.74 for 4.5mm Ti rod, decreasing to 1.41+0.55 for 5.5mm Ti rod, and to 1.09+0.36 for 5.5mm Ti-alloy rod. Mean fusion scores for autograft and allograft subgroups were 2.13±0.72 and 2.14±0.74 respectively. Fusion scores were highest in the middle of implant construct, dropping off by 20–30% toward the ends. Fusion scores adjacent to the rod (2.19±0.72) were significantly higher than on the contralateral side of the disc (1.24±0.85). Levels where rod fracture occurred (n=11) had lower fusion scores than those without fracture (1.09±0.67 vs 1.76±0.80). Levels where top screw pullout occurred (n=6) had lower CT fusion scores than those without (1.25±0.60 vs 1.83±0.76).

Rod diameter (larger), intervertebral level (proximal or distal), lateral position in disc (further from rod) and rod fracture or screw pullout all reduce fusion scores, while graft type does not affect scores. The assumed link between higher fusion score and better clinical outcome must be treated with caution, because rod fractures did not necessarily occur in patients with lower fusion scores. It is possible that with a stiffer rod, less bony fusion mass is required for a stable construct. We propose that moderate fusion scores secure successful clinical outcomes in thoracoscopic scoliosis surgery.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 345 - 345
1 May 2009
Carstens A Meikle G Hodgson B
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Posterior spinal fusion is performed for a variety of lumbar spine conditions for relief of low back pain. Success relies on an effective fusion. Autograft is associated with donor site comorbidity and limited supply. Allograft has the potential for infection and has limited osteoinductive activity. Bone morphogenic proteins (BMPs) have been promoted for use in posterior spinal fusion despite considerable cost and limited evidence to their efficacy.

The aim of this study was to compare the clinical response, donor site morbidity and radiologic rates of fusion in patients undergoing posterior spinal fusion looking at the choice of bone graft or substitute. A retrospective review of 141 patients undergoing instrumented posterior lumbar spinal fusion by a single surgeon for degenerative disc disease, degenerative spondylolithesis or lytic spondylolithesis between 2000 and 2005 was undertaken. Patients were contacted and assessed for donor site morbidity and scored with the Oswestry Disability Index (ODI). Radiographs were taken and assessed by an independent blinded radiologist using the Ferguson score. Simple analysis was performed of these results to compare bone grafting techniques.

One hundred and forty-one patients were available for review. Fusions were performed for lytic spondylolithesis in 12.4%, degenerative spondylolithesis in 46% and for degenerative disc disease in 41.6% of patients. BMP-2 was used in 19.6%, allograft in 59.8% and iliac crest bone graft in 20.5% of patients. The BMP-2 and non BMP-2 groups were equally spread between the diagnosis and levels of surgery. The overall Ferguson score radiographic fusion rates for these patients was A in 67.9%, B in 17.9% and C in 11.9%. The BMP-2 group patients scored 76.9% (A group) and 23.1% (B group). The non-BMP-2 group scored 57.1% (A group), 23.8% (B group) and 19.1% (C group). The Oswestry Disability Index for patients with BMP-2 improved from 49.7% to 19%, whereas with no BMP-2 improved from 50.0% to 20.9%. Donor site morbidity was not identified as a problem in patients who had an autograft procedure.

Over the course of several years a single spinal surgeon’s posterior lumbar spinal fusion practice has evolved as a variety of bone grafting techniques have been trialled in an effort to increase the rate of bony fusion. There was no obvious difference in Oswestry Disability Index score but there was a modest difference in the Ferguson radiologic fusion score for the BMP-2 group. Morbidity in the autograft group was not a problem. These results have confirmed the efficacy of both allograft and autograft in fusion.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 300 - 300
1 Sep 2005
Carstens A Callon K Bava U Pitto R Cornish J
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Introduction and Aims: Regeneration of bone is an important goal in orthopaedic surgery. The repair of a critical skull defect is a model for investigating the efficacy of cell signalling factors and biomaterials in inducing new bone formation. We aim to investigate a 5mm critical skull defect in the mouse, as an in vivo tool for analysis of potential bone active factors that have been bio-prospected from dairy milk protein.

Method: Adult Swiss CD1 mice were divided into two groups. Each group contained animals treated with vehicle (n=11), milk protein (4mg, n=10) and TGF-β1 (2μg, n=6). Under anaesthetic, a high-speed burr was used to create a five-mm craniotomy in the left parietal bone and a pre-cut collagen sponge with 20μl of the test factor inserted. Fluorochrome labels were administered to facilitate quantitative histological analysis of the defect. The animals were sacrificed on days 14 and 28 and the calvariae excised and fixed. The defects were assessed for percent closure using radiography, transillumination and histology.

Results: The formal analysis of this study is underway at present. TGF-β1 has been shown in the literature to augment the healing of critical skull defects and is included in this study as a positive control. Our radiography results show significantly complete closure of the skull defect in TGF-β1 group.

Preliminary work in our laboratory with this milk protein has shown it to be a novel bone active factor. In vivo, local injection above the calvariae in adult mice resulted in significant increase in bone area and dynamic histomorphometric indices of bone formation. In vitro, the protein is anabolic, an effect that is consequent upon its potent proliferative and anti-apoptotic actions in osteoblasts, and its ability to inhibit osteoclastogenesis.

Conclusions: We believe the critical skull defect in the mouse may be a useful means to assess the role of potential bone active factors in wound healing of osseous defects. The purified milk protein tested may have a physiological role in bone growth and a potential therapeutic application in bone regeneration. We await formal analysis of the specimens to further elucidate this statement.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 26 - 27
1 Mar 2005
Carstens A Callon K Bavu U Pitto R Cornish J
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Regeneration of bone is an important goal in orthopaedic surgery, such as in augmentation of fracture healing, spinal fusion and filling of osseous defects. The repair of a critical skull defect is a well-established model for investigating the efficacy of cell signalling factors and biomaterials in inducing new bone formation. We aimed to investigate a 5-mm critical skull defect in the mouse, as an in vivo tool for analysis of potential bone active factors that have been bioprospected from dairy milk protein.

Adult Swiss CD1 mice were divided into 2 groups. Each group contained animals treated with vehicle (n=11), milk protein (4mg, n=10) and TGF-b1 (2μg, n=6). Under anaesthetic a high-speed burr was used to create a 5-mm craniotomy in the left parietal bone and a precut collagen sponge with 20ml of the test factor inserted. Fluorochrome labels were administered to facilitate quantitative histological analysis of the defect. The animals were sacrificed on days 14 and 28 and the calvariae excised and fixed. The defects were assessed for percent closure using radiography, transillumination and histology.

The formal analysis of this study is underway at present. Preliminary work in our laboratory with this milk protein has shown it to be a novel bone active factor. In vivo, local injection above the calvariae in adult mice resulted in significant increase in bone area and dynamic histomorphometric indices of bone formation. In vitro, the protein is anabolic, an effect that is consequent upon its potent proliferative and anti-apoptotic actions in osteoblasts, and its ability to inhibit osteoclastogenesis.

TGF-b1 has been shown in the literature to augment the healing of critical skull defects and is included in this study as a positive control.

We believe the critical skull defect in the mouse may be a useful means to assess the role of potential bone active factors in wound healing.

The purified milk protein used in this study may have a physiological role in bone growth and a potential therapeutic application in bone regeneration. We await formal analysis of the specimens to further elucidate this statement. Further experiments will be required to determine whether it provides results that are reproducible and/or comparable to other models of fracture repair.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 27 - 27
1 Mar 2005
Carstens A Bava U Naot D Callon K Reid I McCowan S Pitto R Cornish J
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Paget’s disease of bone is a common disorder characterised by focal areas of increased bone resorption coupled to increased and disorganised bone formation. Pagetic osteoclasts have been studied extensively, however, due to the integral cross-talk between osteoclasts and osteoblasts, we propose that pagetic osteoblasts may also play a key role in the pathogenesis of Paget’s disease. Any phenotypic changes in the diseased osteoblasts are likely to result from alterations in the expression levels of specific genes. To determine any differences in expression between pagetic and non-pagetic osteoblasts and their precursors the gene expression profiles of RANK, RANKL, OPG, VEGF, IL-1beta, IL-6, MIP-1, TNF and M-CSF were investigated in primary cultures of human osteoblasts and in the osteoblast precursor population of bone marrow stromal cells. We present preliminary data of this study.

Trabecular bone explants were finely chopped, washed free of marrow and cellular debris then either snap frozen in liquid nitrogen or placed in flasks to culture outgrowth osteoblast-like cells. Mononuclear stromal cells from bone marrow were isolated and grown in culture flasks. RNA and conditioned media were collected from cultured osteoblasts and stromal cells at confluency. The innovative method of Real-Time PCR, the most accurate technique available at present to quantitatively measure gene expression, was used for the comparison of gene expression levels in our samples. 18S ribosomal RNA was used as an endogenous control to normalise the expression in the various samples.

RANK, MIP-1 and TNF were only detected in stromal cells whereas RANKL, OPG, VEGF, IL-1beta, IL-6 and M-CSF were detected in both osteoblasts and stromal cells. OPG displayed higher expression in osteoblasts while IL-1beta showed higher expression in stromal cells.

To date we have not seen any significant differences in gene expression between pagetic and non-pagetic subjects when comparing a small number of samples. A larger cohort is currently being investigated. We are also comparing levels of secreted proteins in the conditioned media from pagetic and non-pagetic cell cultures. This may lead to further candidate genes involved in the pathology of the pagetic lesion.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 466 - 466
1 Apr 2004
Pitto R Carstens A Hamer H Heiss-Dunlop W Kuehle J
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Introduction Venous thromboembolic disease is a serious complication of total hip replacement (THR). Use of low-molecular-weight heparin (LMWH) has been shown to reduce the occurrence of deep-vein thrombosis (DVT) significantly, but side effects such as bleeding and thrombocytopenia are frequent. Pneumatic compression with foot-pumps seems to provide the best balance of effectiveness and safety. However, a recent meta-analysis showed that the overall number of patients investigated in randomised clinical trials is too small to draw evidence-based conclusions regarding mechanical prophylaxis of DVT. This trial is a contribution in comparing the effectiveness and safety of mechanical versus chemical prophylaxis of DVT in patients managed with THR.

Methods Inclusion criteria were hip osteoarthritis, age less than 80 years, and uninterrupted use of a foot-pump. Exclusion criteria were a history of thromboembolic disease, heart disease, malignancy and bleeding diatheses. Two hundred and sixteen consecutive patients were considered for inclusion in the trial and were randomized either for management with (LMWH) (Fraxiparin, Sanofi -Synthelabo, France) or with the A-V Impulse foot-pump (Orthofix Vascular Novamedix, UK). All patients started mobilisation on crutches with partial weight-bearing on day two using compression stockings. The foot-pump was applied on both feet in the recovery room and was used until patient discharge. Management with the foot-pump was interrupted only during physiotherapy and toileting. A reverse Trendelenburg position (head-high, feet-low) was applied at rest to enhance the pneumatic effect of the pumps. Patients were monitored for DVT using serial duplex sonography (Sonoline Elegra, Siemens, Germany) at day three, 10 and 45 after surgery.

Results DVT was detected in three of 100 patients managed with the foot-pump compared with six of 100 patients who received chemical prophylaxis. Sixteen patients did not tolerate continuous use of the foot-pump and were excluded from the study. The average post-operative drainage was 259 ml in the foot-pump group and 328 ml in the control group (p=0.05). Patients with foot-pump had less swelling of the thigh (10 mm compared with 15 mm) (p=0.05). One patient developed heparin-induced thrombocytopenia.

Conclusions This study confirms the effectiveness and safety of mechanical prophylaxis of DVT in THR, confirming the outcomes of previous randomized clinical trials. Some patients cannot tolerate the foot-pump, mostly because of sleep disturbance.

In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 466 - 467
1 Apr 2004
Pitto RP Spika I Carstens A
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Introduction Considerable advances have been made in improving cementing techniques in total hip replacement. Recently, the increasing need to minimize healthcare costs has led to the development of methods to reduce surgical time. It has been proposed that the curing time for bone cement can be markedly reduced by preheating the femoral component before insertion. A reduction of the period between insertion of the implant and ultimate curing decreases operative time, bleeding into the bone-cement interface and the likelihood of accidental loss of position. In a previous in-vitro study, preheating the femoral component to a temperature of about 50° resulted in a reduction in the bone cement curing time of approximately 50%. No adverse changes of the mechanical properties of cement were found. E-modulus, fracture toughness and fatigue strength were unaffected by increased temperature. A uniform trend of decreasing porosity of bone cement with increased temperature of the implant was also observed. To-date, there have been no reports on the in-vivo outcome of the preheating cementing technique. The aim of this prospective study was to assess the clinical and radiological five year follow-up results of the preheating cementing technique used for the fixation of the femoral stem (Lubinus, Link, Germany).

Methods One hundred consecutive patients (100 hips) with osteoarthritis and an average age of 72 years (range 65 to 85) have been operated on by one surgeon in a single institution. In a cohort of 50 hips a conventional cementing technique was used. The cement used was Cemex (Tecres, Italy). The anterior-posterior and lateral radiographs have been evaluated with a computer-aided system. The quality of cement mantle was assessed on the radiographs according to the A-B-C1-C2-D classification.

Results The curing time of the bone cement was markedly reduced (average five minutes, range four to seven minutes) by preheating the femoral component (40° to 50°). The estimated reduction of intra-operative blood loss was 75 ml (range 45 to 130). The mean Harris Hip Score was 94.8 points at follow-up (range 79 to 100). The clinical status of 92% of hips was rated good or excellent, eight percent was rated fair. A satisfactory cementing technique was obtained in 96% of hips. Small voids in the cement mantle (grade C1) were present in four percent of hips. Non-progressive radiolucent lines at the bone-cement interface were observed at Gruen zone one in four hips, at zone eight in three hips and at zone 14 in three hips. No signs of osteolysis were observed at follow-up, all stems were rated radiologically stable.

Conclusion A reduction in curing time of bone cement provides a significant time saving without compromising implant performance. We recommend preheating of femoral components to surgeons experienced in joint replacement and have a skilled surgical team, because of the potential risk of premature polymerization before complete seating of the implant.

In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 487 - 487
1 Apr 2004
Carstens A Pitto R Naot D Callon K Reid I Cornish J Bava U
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Introduction Paget’s disease of bone is a common disorder characterised by focal areas of increased bone resorption by osteoclasts and disorganised bone formation by osteoblasts. Because there is integral cross-talk between osteoclasts and osteoblasts during normal bone remodelling, we propose that Pagetic osteoblasts may also play a key role in the pathogenesis of Paget’s disease. Any phenotypic changes in the diseased osteoblasts are likely to result from alterations in the expression levels of specific genes.

Methods To determine any differences in expression between Pagetic and non-Pagetic osteoblasts and their precursors the gene expression profiles of RANK, RANKL, OPG, VEGF, IL-1beta, IL-6, MIP-1, TNF and M-CSF were investigated in primary cell cultures of human osteoblasts and in the osteoblast precursor population of bone marrow stromal cells. Trabecular bone explants were finely chopped, washed free of marrow and cellular debris then either snap frozen in liquid nitrogen or placed in flasks to culture outgrowth osteoblast-like cells. Mononuclear stromal cells from bone marrow were isolated and grown in culture flasks. RNA and conditioned media were collected from cultured osteoblasts and stromal cells at confluency. Real-Time PCR was used for the comparison of gene expression. 18S ribosomal RNA was used as an endogenous control to normalise the expression in the various samples.

Results RANK, MIP-1 and TNF were only detected in stromal cells whereas RANKL, OPG, VEGF, IL-1beta, IL-6 and M-CSF were detected in both osteoblasts and stromal cells. OPG displayed higher expression in osteoblasts while IL-1beta showed higher expression in stromal cells. To-date we have not seen any significant differences in gene expression between pagetic and non-pagetic subjects when comparing a small number of samples. A larger cohort is currently being investigated. Mutations in the sequestosome 1 gene have been showed to be associated with Paget’s disease. When a small number of Pagetic samples were sequenced for these mutations we found one out of seven patients (14%) to possess a known transition mutation at position 1215 in this gene.

Conclusions These results may further our understanding of the pathology of Paget’s disease.