Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases.

This multicenter study assessed the safety and efficacy of teriparatide 20 microg/day in Japanese men and women with osteoporosis at high risk of fracture during a 12-month, randomized, double-blind, placebo-controlled treatment period followed by second and third treatment periods (to 18 and 24 months, respectively,) in which all subjects received open-label teriparatide. Subjects (93% female; median age 70 years) were randomized 2:1 to teriparatide versus placebo (randomized at baseline, teriparatide n=137, placebo-teriparatide n=70; entering the second period, teriparatide n=119, placebo-teriparatide n=59; entering the third period, teriparatide n=102, placebo-teriparatide n=50). For subjects with measurements at 12 months, teriparatide significantly increased bone mineral density (BMD) at the lumbar spine L2-L4 (mean percent change+/-SD, teriparatide 10.04+/-5.23% versus placebo-teriparatide 0.19+/-4.33%), the femoral neck (teriparatide 2.01+/-4.63% versus placebo-teriparatide 0.44+/-3.97%), and the total hip (teriparatide 2.72+/-4.04% versus placebo-teriparatide -0.26+/-3.42%). In the placebo-teriparatide group at 24 months (12-month teriparatide dosing) BMD increased by 9.11+/-5.14% at the lumbar spine, 2.19+/-4.81% at the femoral neck and 2.46+/-3.54% at the total hip. In the teriparatide group at 18 and 24 months, BMD increased from baseline at the lumbar spine by 11.93+/-5.79% and 13.42+/-6.12%, respectively; at the femoral neck by 2.68+/-4.45% and 3.26+/-4.25%, respectively; and at the total hip by 3.02+/-3.79% and 3.67+/-3.98%, respectively. Serum procollagen I N-terminal pro-peptide (PINP) increased rapidly with teriparatide treatment (P<0.001 versus placebo at 1 month) and changed from baseline in the teriparatide and placebo-teriparatide groups at 12 months by a median of 78.95% and -17.23%, respectively, (P<0.001) and at 24 months by 49.24% and 76.12%, respectively. The incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs were comparable in the teriparatide and placebo-teriparatide groups. These data show that teriparatide 20 microg/day was well tolerated and stimulated bone formation in Japanese subjects with osteoporosis at high risk of fracture during 18 and 24 months of treatment.