Martin J. Shelly MD, Presenter: Nothing to Disclose

Julie Marie O'Brien MBBCh, Abstract Co-Author: Nothing to Disclose

Peter MacMahon MBBCh, Abstract Co-Author: Nothing to Disclose

Stephen John Eustace MD, Abstract Co-Author: Nothing to Disclose

Regulation of total osteoblast number is the major pathogenomic mechanism of altered bone density. Reduction of osteoblast numbers via apoptosis is thought to play an important role in the decrease in bone mineral density (BMD) that characterises osteoporosis. In this study we have utilised a complementary in vitro and ex vivo based strategy to identify those apoptosis genes whose expression drives osteoporosis.

Using oligonucleotide microarrays we have identified a cohort of apoptosis associated genes whose expression is altered in vitro. These genes include tumour necrosis factor alpha (TNFα), FAS ligand, Caspase 3 and BCL 10. Having identified these genes as being putative molecular drivers of altered bone density we sought to characterise their expression in ex vivo serum samples from a cohort of 40 patients who were identified on DEXA scan as having either 1) normal bone density (t score > -1), 2) osteopenia (t score between -1 and -2.5) or 3) osteoporosis (t score < -2.5). Circulating levels of secreted markers of apoptosis were determined for each group using an ELISA based strategy.

Our results demonstrated a correlation between bone density and circulating levels of apoptotic markers. The highest levels of apoptotic markers were found in the serum of patients who were osteoporotic. Conversely, patients with normal BMD had the lowest levels of apoptotic markers.

In aggregate, the data presented herein further validate the role of apoptosis in the pathogenesis of osteoporosis. Furthermore, a correlation is demonstrated between circulating levels of apoptotic markers and BMD, as determined by DEXA scanning.

Patients with abnormal bone mineral density display elevated levels of apoptosis biomarkers that provide a potential target for gene therapy of osteoporosis.

Shelly, M, O'Brien, J, MacMahon, P, Eustace, S, Apoptosis Genes: Potential Biomarkers for Osteoporosis.  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/6010046.html