Abstract
The cellular and molecular mechanisms that lead to particular trabecular structures in healthy bone and in skeletal disease, such as osteoarthritis (OA), are poorly understood. Osteoclast differentiation factor (ODF) is a newly described regulator of osteoclast formation and function, whose activity appears to be a balance between interaction with its receptor, RANK, and with an antagonist binding protein, osteoprotegerin (OPG). We have examined the relationship between the expression of ODF, RANK and OPG mRNA, and parameters of bone structure and turnover, in human trabecular bone. Intertrochanteric trabecular bone was sampled from patients with primary hip OA (n=13; median age 66 years) and controls taken at autopsy (n=12; median age 68.5 years), processed for histomorphometric analysis and RNA isolated for RT-PCR analysis of ODF, RANK and OPG mRNA expression. The ratios of ODF/OPG and ODF/RANK mRNA are significantly lower in OA (1.78±0.98; 0.59±0.31) compared to the controls (3.41±1.94, p< 0.02; 2.53±1.5, p< 0.001). This suggests that in OA there is less ODF mRNA available per unit RANK mRNA, and that osteoclast formation may be reduced. Furthermore, eroded bone surface (ES/BS[%]) was significantly lower (p< 0.05) in the OA group (6.37±3.17) compared to controls (9.74±4.53). Stong associations were found between the ratio of ODF/OPG mRNA and bone volume (ODF/OPG vs BV/TV[%], r=−0.67; p0.05) and bone turnover (ODF/OPG vs ES/BS, r=0.93; p< 0.001; ODF/OPG vs osteoid surgace (OS/BS[%], r=0.80; p< 0.001) in controls. In contrast to controls, these relationships were not evident in the OA group, suggesting that bone turnover maybe regulated differently in this disease.
The abstracts were prepared by Professor Jegan Krishnan. Correspondence should be addressed to him at the Flinders Medical Centre, Bedford Park 5047, Australia.
