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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. 85-B, Issue SUPP_III | Pages 202 - 202
1 Mar 2003
Brick M McCowan S
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Surgeons are becoming increasingly aware of the importance of matching a patient’s native offset during hip arthroplasty. During the course of a previous study investigating proximal femoral geometry in New Zea-landers it was noted that accurately measuring the femoral offset of a hip arthroplasty patient by traditional methods is difficult and inaccurate. The relationship of various surface parameters were studied to find a simple and reliable method for the surgeon.

Eighteen cadaver femora were skeletalised and the offset was measured using a standardised radiological technique. The femoral neck was then sectioned from a point 1–2 cm above the lesser trochanter to the base of the trochanteric fossa. The femoral head was sectioned in the coronal plane and the centre of the head located with concentric circles. The distance from the centre of the head to the most lateral spike of bone was measured. This measure was compared to the radiological offset.

Offset correlated closely with the measurement from the centre of rotation to the most lateral spike of bone provided the neck cut extends to the base of the tro-chanteric fossa. Eleven of eighteen measurements were within 2mm of true offset and fifteen were within 3mm. A simple intra-operative technique taking no longer than one or two minutes and requiring no special equipment has been devised to allow the surgeon to accurately estimate the patients femoral offset.