SERUM OSTEOCALCIN AND BONE ISOENZYME ALKALINE-PHOSPHATASE IN GROWTH HORMONE-DEFICIENT PATIENTS - DOSE-RESPONSE STUDIES WITH BIOSYNTHETIC HUMAN GH

Serum osteocalcin and bone alkaline phosphatase (BAP) were measured in samples drawn at 8 a.m. in 7 patients with GH deficiency treated with recombinant human growth hormone (rhGH) (2 IU/day subcutaneously at 8 p.m.), and 7 normal controls. Patients treated with 2 IU/day had lower BAP than controls (P < 0.05). Further, increasing doses of rhGH were given subcutaneously to each of the 7 patients for 3 consecutive 14-day periods (2,4, and 6IU/day at 8 p.m.) followed by 14 days off treatment. At the end of each period, the patient was hospitalized for frequent blood sampling from 8 p.m. to 11 a.m. the following day. A dose-dependent increase in area under the curve (AUC) was seen for osteocalcin (P < 0.05), whereas the increase in AUC for BAP just failed to reach significance (P < 0.10). The nocturnal patterns of serum osteocalcin in patients on 4 and 6 IU/day were statistically indistinguishable from those in controls. During treatment with 2 IU/day and the off-treatment period, the pattern was significantly different from controls (P < 0.05). In conclusion, rhGH has a dose-dependent effect on basal osteoblastic activity and the nocturnal pattern of osteocalcin. Serum osteocalcin increases within hours following rhGH administration. However, 2 IU/day is inadequate to maintain normal levels and nocturnal variation in markers of osteoblastic activity.