In a 12-month randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover. Twenty-eight men with idiopathic osteoporosis aged 27-74 years (mean, 52.4 years) were randomized to receive either nasal SCT (200 IU) or a nasal placebo daily for a period of 1 year. All the men received a daily supplement of 0.5 g of calcium. The men who received SCT had a mean (+/-SEM) increase in BMD of 7.1 +/- 1.7% at the lumbar spine. In contrast, the men who received the placebo had an increase of 2.4 +/- 1.5% (p > 0.05) for the comparison with baseline. The increase in lumbar BMD in the calcitonin group was significantly greater than that in the placebo group (p < 0.05). There were no significant changes in the femoral neck, trochanter, or Ward's triangle relative to both baseline and placebo after 12 months. Treatment with nasal SCT resulted in a significantly pronounced suppression of bone resorption markers (urinary deoxypyridinoline [DPD], type I cross-linked N-telopeptide [NTX], and type I cross-linked C-telopeptide [CTX]) and to a lesser extent in bone formation markers (serum bone-specific alkaline phosphatase [BALP], osteocalcin [OC], serum C-terminal procollagen type I extension peptides [PICP], and serum N-termnal procollagen type I extension peptides [PINP]), whereas the placebo did not. Therapy was tolerated well and there were no treatment-related adverse events. We conclude that intranasal SCT (200 IU daily) is safe and effective in increasing lumbar BMD and reducing bone turnover in men with idiopathic osteoporosis.