2 μg) Teriparatide group (56.5 μg) Item Time Median Max Min Median Max Min Median Max Min Intact-PTH (pg/mL) Baseline 33.5 53.0 24.0 34.5 50.0 28.0 42.5 52.0 32.0 2 to 24 h 43.0 75.0 22.0 34.5 66.0 17.0 35.0 65.0 18.0 4 to 15 days 46.5 81.0 27.0 45.5 64.0 25.0 49.0 109.0 26.0 1,25(OH)2D (pg/mL) Baseline 56.5 79.0 33.0 53.0 79.0 34.0 63.5 75.0 40.0 2 to 24 h 54.0 93.0 26.0 67.5 118.0 37.0 70.5 136.0 33.0 4 to 15 days 61.0 95.0 29.0 56.0 99.0 21.0 54.0 94.0 18.0 Serum osteocalcin (ng/mL) Baseline 9.6 13.4 7.3 8.8 12.5 LY3009104 5.4 9.2 15.8 4.2 2 to 24 h 8.6 13.6 5.5 7.6 12.7 4.6 7.4 16.7 3.2 4 to 15 days 8.6 12.4 4.8 8.1 12.2 4.6 7.9 17.9 4.3 Serum P1NP (ng/mL)

Baseline 62.9 90.2 39.8 52.8 81.3 32.8 59.5 109.0 21.1 2 to 24 h 53.5 91.4 36.0 47.4 77.4 28.0 49.1 101.0 13.0 4 to 15 days 51.6 89.4 31.0 53.5 80.2 30.7 56.9 118.0 18.3 Serum NTX (nM BCE/L) Baseline 12.7 22.8 11.1 13.9 19.0 9.5 13.1 19.6 10.9 2 to 24 h 11.8 24.5 7.4 14.2 21.7 9.2 13.8 27.7 7.2 4 to 15 days 13.1 22.7 8.3 13.2 20.4 7.2 10.7 20.6 7.5 Urinary CTX (μg/mmol) Baseline 358.0 798.0 275.0 376.5 746.0 268.0 487.0 736.0 272.0 2 to 24 h 301.0 679.0 92.7 402.5 958.0 192.0 508.5 1190.0 238.0 4 to 15 days 374.0 722.0 202.0 351.0 655.0 106.0 351.0 972.0

142.0 PTH parathyroid hormone, P1NP procollagen type I N-terminal propeptide, NTX cross-linked N-telopeptide find more of type I collagen, CTX cross-linked C-telopeptide of type I collagen Changes in bone formation markers Percent change from baseline and percent changes subtracted by the corresponding placebo values were calculated for serum P1NP and osteocalcin. Nutlin-3 cell line In the placebo group, serum levels of

P1NP and osteocalcin were increased after injection followed by a gradual decrease to ~15 % below baseline (Fig. 4a–d). There were no remarkable dose-related differences in P1NP changes. Serum osteocalcin levels followed a similar trend Saracatinib ic50 including a dose-dependent response. However, the late-phase increase was not as obvious (+10 %).