Objective: To investigate the incidence of osteoporotic fractures and effects on bone of low-dose glucocorticoid (GC) monotherapy in a group of previously untreated patients with early active RA we performed a double blind, randomised, placebo-controlled clinical trial. The study duration was 2 years, with an open follow-up during the third year. Patients were randomly allocated to receive 10 mg prednisone or placebo.
Methods: Non-steroidal anti-inflammatory drugs (NSAIDs) were allowed in both groups. After 6 months sulphasalazine (2 gr daily) could be prescribed as rescue therapy in both groups. Except for 500 mg calcium supplement daily, no specific preventive measures were taken. This was a normal procedure at the time the study was designed (1989-1991). At the start of the study and every 6 months, X-rays of the twelfth thoracic and of all lumbar vertebrae were scored using the Kleerekoper method, and every year biochemical parameters of bone metabolism and bone mineral density (BMD, expressed in T-scores) and bone mineral content (BMC, expressed in g/cm) were assessed.
Results: In the prednisone group there was a higher incidence during the study of lumbar vertebral fractures than in the placebo group: 7 vs 4 respectively. This difference did not reach statistical significance however, probably because of the small numbers. One patient of the prednisone group suffered an osteoporotic fracture of the pelvis. In the 2-year study and the subsequent follow-up year, no other peripheral fractures were seen in either group. No significant changes from baseline in BMD and BMC of the hips were seen in either group during the study and the follow-up year. In the lumbar spine, BMD in the prednisone group decreased although not statistically significantly during the whole study. No correlation between changes in serum osteocalcin and BMD was observed.
Conclusion: Low-dose prednisone monotherapy for patients with early active previously untreated RA seems to increase the risk of fractures not only by reducing the BMD but also by changes in bone strength and structure.