(a)
(b)
Figure 3: Change in serum concentrations of P1NP after multiple doses of anti-sclerostin antibodies in cynomolgus monkeys (a) and humans (b). (a) After 30 mg/kg, subcutaneous dose of romosozumab P1NP levels (a marker of bone formation) increases in cynomolgus monkeys. Subsequently, P1NP levels decline before increasing subsequent to the second dose of romosozumab on day 29 (day of administration delineated by “X”). (b) This sharply contrasts with median levels of P1NP observed in human subjects after monthly doses of 210 mg (total monthly dose) of blosozumab over a 12-month period. Here a sharp increase in P1NP is observed after initial administration which peaks after the second subcutaneous injection of romosozumab at 1 month. Despite subsequent monthly doses, P1NP levels continue to decline and were observed to fall below baseline levels after 7 months, where levels remained until 12 months (demarcated the end of the study) [images adapted from [52] (a) and [55] (b)].