TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH CONTINUOUS DAILY ORAL ALENDRONATE IN COMPARISON WITH EITHER PLACEBO OR INTRANASAL SALMON-CALCITONIN

Alendronate sodium (ALN) is a potent amino bisphosphonate which specifically inhibits osteoclastic bone resorption and has been found to reverse bone loss in several animal models. To determine if daily oral ALN treatment could prevent or reverse bone loss in osteoporotic postmenopausal women, and to compare ALN to intranasal salmon calcitonin (CT), a 2-year, double-masked, randomized, placebo-controlled study was initiated at 9 clinical centers in Italy. Two hundred and eighty six post-menopausal women (age 48-76) with spinal bone mineral density (BMD) greater-than-or-equal-to 2 SD below adult mean peak, with or without vertebral crush fractures, were randomized to one of four treatment arms: ALN 10 mg daily, ALN 20 mg daily or matching placebo (these groups all double-masked), or CT 100 IU daily (open label) for 2 years. All patients received supplemental calcium (as carbonate) 500 mg daily. Bone mass was measured by dual-energy X-ray absorptiometry of the PA lumbar spine (LS) and proximal femur (femoral neck and trochanter) at 6-month intervals. Subject safety was measured through sequential clinical and laboratory evaluation. A planned 1-year interim analysis of this ongoing study was performed cetrally in a manner that maintains the double-mask for all subjects receiving oral study drug. Relative to PBO, ALN at either 10 mg or 20 mg daily increased LS BMD by 4.7% and 6.1%, respectively; each increased femoral neck BMD by 3.1% and increased trochanter BMD by 3.3% and 3.8% respectively. In contrast, CT failed to significantly increase BMD of either the spine, femoral neck or trochanter, either relative to baseline or to PBO. ALN decreased biochemical markers or bone turnover, whereas both PBO and CT were ineffective. No serious adverse experiences attributable to the use of alendronate were detected. In summary, daily oral ALN for one year appears to be effective in decreasing bone turnover and increasing bone mass at the spine and the hip. In contrast, daily CT 100 IU had no significant effects either to reduce bone turnover or to increase bone mass at either site. In conclusion, ALN effectively increased bone mass in osteoporotic menopausal women, and was associated with an excellent safety profile.