Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 +/- 1.0% (mean +/- SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 +/- 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 +/- 1.0% and 2.0 +/- 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 +/- 2.2 vs. 12.2 +/- 1.1%, 1.2 +/- 0.7 vs. 2.6 +/- 0.7%, and 20.7 +/- 6.2 vs. 13. 7 +/- 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 +/- 5.2 vs. 18.8 +/- 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.