Research article

Circulating RANKL is inversely related to RANKL mRNA levels in bone in osteoarthritic males

David Findlay^1,2 , Mellick Chehade^1,2 , Helen Tsangari³ , Susan Neale^1,2 , Shelley Hay^1,2 , Blair Hopwood³ , Susan Pannach^1,2 , Peter O'Loughlin⁴ and Nicola Fazzalari^2,3,5

¹  Discipline of Orthopaedics and Trauma, University of Adelaide, North Terrace, Adelaide, 5000, Australia

²  Hanson Institute, Frome Road, Adelaide, 5000, Australia

³  Division of Tissue Pathology, Institute of Medical and Veterinary Science, Frome Road, Adelaide, 5000, Australia

⁴  Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Frome Road, Adelaide, 5000, Australia

⁵  Discipline of Pathology, University of Adelaide, North Terrace, Adelaide, 5000, Australia

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R2doi:10.1186/ar2348

Published:	8 January 2008

Abstract

Introduction

The relationship of circulating levels of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) with the expression of these molecules in bone has not been established. The objective of this study was to measure, in humans, the serum levels of RANKL and OPG, and the corresponding levels in bone of mRNA encoding these proteins.

Methods

Fasting blood samples were obtained on the day of surgery from patients presenting for hip replacement surgery for primary osteoarthritis (OA). Intraoperatively, samples of intertrochanteric trabecular bone were collected for analysis of OPG and RANKL mRNA, using real time RT-PCR. Samples were obtained from 40 patients (15 men with age range 50 to 79 years, and 25 women with age range 47 to 87 years). Serum total RANKL and free OPG levels were measured using ELISA.

Results

Serum OPG levels increased over the age range of this cohort. In the men RANKL mRNA levels were positively related to age, whereas serum RANKL levels were negatively related to age. Again, in the men serum RANKL levels were inversely related (r = -0.70, P = 0.007) to RANKL mRNA levels. Also in the male group, RANKL mRNA levels were associated with a number of indices of bone structure (bone volume fraction relative to bone tissue volume, specific surface of bone relative to bone tissue volume, and trabecular thickness), bone remodelling (eroded surface and osteoid surface), and biochemical markers of bone turnover (serum alkaline phosphatase and osteocalcin, and urinary deoxypyridinoline).

Conclusion

This is the first report to show a relationship between serum RANKL and the expression of RANKL mRNA in bone.