Purpose: To compare the bone-mass effects of calcium supplementation and intermittent cyclic etidronate in patients with established corticosteroid-induced osteoporosis.
Patients and methods: Eighteen male and 21 female patients who had established corticosteroid-induced osteoporosis and were receiving chronic prednisone therapy (> or = 10 mg/d) were enrolled in a prospective 12-month, open-label study. In addition to continuing prednisone therapy, patients received continuous calcium supplementation 500 mg/d (n = 20) or four cycles of intermittent cyclic etidronate therapy consisting of etidronate 400 mg/d for 14 days followed by calcium 500 mg/d for 76 days (n = 19). Bone mineral density (BMD) of the spine (L1 through L4) and proximal femur (total hip, femoral neck, trochanter, Ward's triangle) was measured by dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months by staff blinded to the treatment. Serum calcium, phosphorus, and alkaline phosphatase were also measured at these times.
Results: Treatment with intermittent cyclic etidronate for 12 months resulted in significant increases of 5.7% and 6.8% in BMD of the spine and proximal femur (total hip), respectively (P < 0.02 versus baseline; P < 0.001 versus calcium group). Calcium supplementation alone did not prevent significant losses of 3.4% and 4.1% in BMD at the respective sites (P < 0.02 versus baseline). At the end of the study Z scores reflected significant increases in BMD of the spine and proximal femur (all regions) in the etidronate group (P < 0.01), and significant decreases at the spine, proximal femur, and trochanter in the calcium group (P < 0.01). After 12 months, the difference between the groups was 9.1% (P < 0.01; 95% CI 6.3% to 11.9%) at the spine and 10.9% (P < 0.01; 95% CI 7.8% to 14.1%) at the proximal femur (total hip). Seventeen (89%) of the etidronate-treated patients had increases in BMD of both skeletal sites, whereas only 2 (10%) and 3 (15%) of the calcium-treated patients had positive changes in BMD of the spine and proximal femur (total hip), respectively (P < 0.01). Serum calcium, phosphorus, and alkaline phosphatase levels did not change significantly during the study in either treatment group. Both treatment regimens were well tolerated, with no interactions between prednisone therapy and the study medications. Analyses of response by subgroups (female/male, pulmonary/nonpulmonary indication for prednisone) showed no significant attribute-dependent changes during the 12-month study. At baseline, women had significantly lower BMD of the spine and proximal femur (total hip) (P < 0.01), and patients with pulmonary disease had significantly longer duration of prednisone therapy and cumulative prednisone dose (P < 0.03).
Conclusions: Intermittent cyclic etidronate reversed the progressive loss of bone mineral density of the spine and proximal femur in female and male patients with established osteoporosis secondary to chronic corticosteroid (prednisone) therapy for pulmonary and nonpulmonary diseases. Calcium supplementation alone did not prevent or attenuate corticosteroid-induced losses.