Date of Award

2012

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor TC Lee

Funder/Sponsor

Higher Education Authority in Ireland and Research Committe of RCSI

Keywords

Bone Diseases

Abstract

Sheep are a practical model for postmenopausal pathologies and have been used for investigation of a number of conditions to date, including the bone diseases osteoporosis and osteoarthritis (Newton, 2004; Parker et al, 2003; Thorndike et al, 1998). With regard to many of the structural parameters, the ovine stifle joint may be considered to be a 1:3 scale model of the human knee joint (Osterhoff et al, 2010). 23 sheep were examined in this study; 10 of the sheep underwent ovariectomy (OVX), while the remainder (n=13) were kept as controls (CON). Five fluorochrome dyes were administered intravenously at 12 week intervals via the jugular vein to both groups, to label sites of bone turnover. These animals were then sacrificed at 12 months postoperatively.

My data showed significant alterations within the subchondral trabecular architecture at one-year post-ovariectomy, with reduced bone volume fraction, thinning of individual trabeculae and an increase in trabecular separation; these findings are consistent with those elsewhere in the ovine skeleton (Cornish et al., 2006; Jiang et al, 2005; Mitton et al., 1998; Mittra et al., 2005; Nafei et al., 2000; Newton et al., 2004; Schorlemmer et al., 2003). In addition, I confirmed that bone turnover was significantly higher in both trabecular bone and the subchondral bone plate at one-year postovariectomy. Remodelling of trabecular bone was due to both classically described hemi-osteonal and intra-trabecular osteonal remodelling, while osteons within the subchondral plate have relatively late mineralisation of lamellae.

The presence of osteopenia and elevated subchondral bone turnover within the medial tibial plateau provides a possible mechanism for subchondral microfractures in the aetiology of spontaneous osteonecrosis of the knee (SPONK). Further utilisation of the ovariectomised ewe would be useful for further study in this field.

I was unable to detect any measurable difference in osteoarthritis between the two study groups. While previous studies have suggested a link between trabecular thinning and osteoarthritis, I was unable to confirm this. Osteoarthritis was associated with a thinning of the subchondral plate, specifically the subchondral cortical bone. I found no correlation between bone turnover rates of either the subchondral trabecular bone or bone plate with osteoarthritis. I conclude that while ovariectomy may not increase the risk of osteoarthritis per se, it will cause osteopenia; if osteoarthritis then occurs, the synergy between these two disease processes will mean that the osteoarthritis in the ovariectomised group will be more severe.

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Comments

Submitted for the Award of Doctor of Philosophy (PhD) to the Royal College of Surgeons, 2012.

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