Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial

Introduction: Alendronate has been described to have a bone-sparing effect in patients treated with moderate and high dosages of prednisone for heterogeneous diseases, however no data are available on groups of patients with the same underlying diseases who receive chronic low-dose prednisone treatment. The objective of the investigation reported here was, therefore, to study the effect of alendronate on bone mineral density (BMD) of the lumbar spine and hips in patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone treatment. Methods: A total of 163 patients with RA, according to the ACR-criteria, were enrolled in a double-blind, placebo-controlled trial. The patients were treated with low-dose prednisone (>= 10 mg/day) for at least 3 months. The patients were randomized to receive daily doses of alendronate or placebo: men and premenopausal women received 5 mg alendronate (or placebo) daily; postmenopausal women received 10 mg alendronate (or placebo) daily. All patients received daily calcium (500 mg, or 1000 mg, depending on baseline dietary calcium intake) and vitamin D-3 (400 IU) supplementation. BMD of the lumbar spine (L1-L4) and the (total) hip was measured at baseline and after 6 and 12 months. The primary endpoint was change in BMD of the lumbar spine after 12 months (ITT). At baseline and after 3 and 12 months, serum bone-specific alkaline phosphatase (BAP) and urinary excretion of N-telopeptide (NTX) were measured. Radiographs of the thoracic and lumbar spine were made at baseline and after 12 months and subsequently scored for vertebral deformities. Results: The groups were comparable at baseline in age, gender, daily dosage of prednisone, BMD at the spine and the hip and markers of bone turnover, while the number of patients with prevalent vertebral deformities was slightly higher in the alendronate-treated patients (54% versus 39%, not significant). After 12 months, BMD at the lumbar spine had increased by 3.7% in the alendronate-treated patients and decreased by -1.0% in the placebo-treated patients (p < 0.0001); at the hip, the changes were +1.0% and -0.1%, respectively (not significant). After 3 months, serum BAP had decreased by 16.9% in the alendronate group versus 3.3% in the placebo group (p=0.0005), while urinary NTX had decreased by 46.4% in the alendronate group versus 12.1% in the placebo group (p < 0.0001). After 12 months, no statistically significant difference was found between the groups with respect to number of patients with incident vertebral or non-vertebral fractures. Adverse effects were relatively common in these patients with severe RA: adverse effects were observed in 68% of the alendronate-treated patients and in 73% of the placebo patients (not significant), while serious adverse events were observed in 13% and 17%, respectively (not significant). Conclusion: We observed a favourable effect of alendronate on the BMD of the lumbar spine and on the markers of bone turnover in patients with RA treated with low-dose prednisone. These data support the conclusion that the prescribing of alendronate is not only beneficial in patients treated with high-dose prednisone but also in RA patients chronically treated with low-dose prednisone.