0021-972X/90/7004-0916I02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1990 by The Endocrine Society
Vol. 70, No. 4 Printed in U.S.A.
Effects of Growth Hormone (GH) on Plasma Bone Gla Protein in GH-Deficient Adults* JULIA SIDENIUS JOHANSEN, S$)REN ANKER PEDERSEN, JENS OTTO L. J^RGENSEN, BENTE JUEL RIIS, CLAUS CHRISTIANSEN, JENS SANDAHL CHRISTIANSEN, NIELS E. SKAKKEB^K Department of Clinical Chemistry, Glostrup Hospital (J.S.J., B.J.R., C.C.), Glostrup; the Department of Paediatrics, Hvidovre Hospital, University of Copenhagen (S.A.P., N.E.S.), Copenhagen; and the Second University Clinic of Internal Medicine, Arhus Kommunehospital, (J.O.L.J., J.S.C.), Arhus, Denmark
ment with human GH, plasma BGP (and other nonspecific biochemical markers of bone turnover) increased significantly (P < 0.001). During placebo treatment plasma BGP showed baseline values. In the acromegalic patients a significant decrease in plasma BGP concentrations was seen 1 week after surgery. The present study suggests that plasma BGP is a useful biochemical marker of the effect of treatment of both GH deficiency and GH excess/disorders. (J Clin Endocrinol Metab 70: 916-919, 1990)
ABSTRACT. Both deficiency and excess of GH are related to disturbances in calcium metabolism. Bone Gla protein (BGP) is the only specific marker of bone turnover identified in peripheral blood. We, therefore, determined plasma BGP in 21 adult GHdeficient patients treated with biosynthetic human GH in a double blind cross-over study. We also examined 9 patients with acromegaly before and after surgery. The GH-deficient patients had normal initial plasma BGP concentrations, whereas the acromegalic patients had highly significantly increased concentrations (P < 0.001). During treat-
R
resorption in a group of adults with GH deficiency before and after treatment with synthetic hGH. The effect on serum BGP in patients with acromegaly before and after surgical intervention is also shown.
ECOMBINANT DNA techniques have increased the availability of human GH (hGH), thereby rapidly expanding the potential number of indications and criteria for treatment (1, 2). The treatment is both expensive and tedious, and its effect on growth can only be assessed after several months. Reliable biochemical markers of bone turnover are thus important for early assessment of the skeletal effects exerted by GH treatment in both children and adults. Bone Gla protein (BGP; osteocalcin) is a major noncollagenous protein of the bone matrix, specifically secreted by osteoblasts (3). Besides occurring in bone matrix, BGP circulates in blood, and its plasma level is believed to reflect the rate of bone turnover, more specifically the rate of bone formation (4-7). One in vitro study has recently shown that insulin-like growth factor-I stimulates BGP synthesis 1.5-2.5 times (8). Cross-sectional studies have demonstrated low levels of serum BGP in children with GH deficiency (9) and high serum BGP levels in patients with acromegaly (10, 11). We here present data on plasma BGP and biochemical parameters commonly used as estimates of bone
Subjects and Methods Patients with GH deficiency Thirteen men and eight women, aged 18-29 yr, were studied. Patient data and study design have been reported previously (12,13). Eleven of the patients had isolated GH deficiency, and 10 had panhypopituitarism. All had previously received GH therapy during childhood and adolescence; in all patients the therapy was discontinued at least 6 months before the present study. GH deficiency was defined as a peak serum concentration of GH less than 5 ng/mL in response to reevaluation with clonidine stimulation (75 mg/m2). The study was a double blind, placebo-controlled cross-over trial. After baseline examinations the patients were randomly allocated to 4 months of treatment with either hGH (Norditropin, Novo-Nordisk A/S, Copenhagen, Denmark; 2 IU/m2 body surface given sc daily at 2000 h) or placebo. To avoid any carryover effects a period of 4 months elapsed before cross-over took place. Examinations were performed at baseline and after each 4-month treatment period.
Received October 20,1989. Address all correspondence and requests for reprints to: Julia Sidenius Johansen, Department of Clinical Chemistry, Glostrup Hospital, DK-2600 Glostrup, Denmark. * This work was supported by grants from the Ib Henriksens Fond.
Patients with acromegaly Seven men and two women, aged 21-73 yr, were studied. Acromegaly was diagnosed on typical clinical presentation and 916
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 21 November 2015. at 14:15 For personal use only. No other uses without permission. . All rights reserved.
PLASMA BGP IN GH-DEFICIENT ADULTS elevated serum concentrations of GH, which were not suppressed during oral glucose load. High resolution computerized tomography confirmed pituitary tumor in each patient. None of the patients had kidney or liver disease. Blood samples were taken immediately before and 1 week after surgery. In all patients blood samples were taken and urine collected in the morning after an overnight fast. All samples were stored at —20 °C until analyzed. Plasma/serum BGP was determined by RIA (14). Antiserum was raised in rabbits immunized with purified intact calf BGP, BGP z score
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Vol. 70, No. 4 Printed in U.S.A.
Effects of Growth Hormone (GH) on Plasma Bone Gla Protein in GH-Deficient Adults* JULIA SIDENIUS JOHANSEN, S$)REN ANKER PEDERSEN, JENS OTTO L. J^RGENSEN, BENTE JUEL RIIS, CLAUS CHRISTIANSEN, JENS SANDAHL CHRISTIANSEN, NIELS E. SKAKKEB^K Department of Clinical Chemistry, Glostrup Hospital (J.S.J., B.J.R., C.C.), Glostrup; the Department of Paediatrics, Hvidovre Hospital, University of Copenhagen (S.A.P., N.E.S.), Copenhagen; and the Second University Clinic of Internal Medicine, Arhus Kommunehospital, (J.O.L.J., J.S.C.), Arhus, Denmark
ment with human GH, plasma BGP (and other nonspecific biochemical markers of bone turnover) increased significantly (P < 0.001). During placebo treatment plasma BGP showed baseline values. In the acromegalic patients a significant decrease in plasma BGP concentrations was seen 1 week after surgery. The present study suggests that plasma BGP is a useful biochemical marker of the effect of treatment of both GH deficiency and GH excess/disorders. (J Clin Endocrinol Metab 70: 916-919, 1990)
ABSTRACT. Both deficiency and excess of GH are related to disturbances in calcium metabolism. Bone Gla protein (BGP) is the only specific marker of bone turnover identified in peripheral blood. We, therefore, determined plasma BGP in 21 adult GHdeficient patients treated with biosynthetic human GH in a double blind cross-over study. We also examined 9 patients with acromegaly before and after surgery. The GH-deficient patients had normal initial plasma BGP concentrations, whereas the acromegalic patients had highly significantly increased concentrations (P < 0.001). During treat-
R
resorption in a group of adults with GH deficiency before and after treatment with synthetic hGH. The effect on serum BGP in patients with acromegaly before and after surgical intervention is also shown.
ECOMBINANT DNA techniques have increased the availability of human GH (hGH), thereby rapidly expanding the potential number of indications and criteria for treatment (1, 2). The treatment is both expensive and tedious, and its effect on growth can only be assessed after several months. Reliable biochemical markers of bone turnover are thus important for early assessment of the skeletal effects exerted by GH treatment in both children and adults. Bone Gla protein (BGP; osteocalcin) is a major noncollagenous protein of the bone matrix, specifically secreted by osteoblasts (3). Besides occurring in bone matrix, BGP circulates in blood, and its plasma level is believed to reflect the rate of bone turnover, more specifically the rate of bone formation (4-7). One in vitro study has recently shown that insulin-like growth factor-I stimulates BGP synthesis 1.5-2.5 times (8). Cross-sectional studies have demonstrated low levels of serum BGP in children with GH deficiency (9) and high serum BGP levels in patients with acromegaly (10, 11). We here present data on plasma BGP and biochemical parameters commonly used as estimates of bone
Subjects and Methods Patients with GH deficiency Thirteen men and eight women, aged 18-29 yr, were studied. Patient data and study design have been reported previously (12,13). Eleven of the patients had isolated GH deficiency, and 10 had panhypopituitarism. All had previously received GH therapy during childhood and adolescence; in all patients the therapy was discontinued at least 6 months before the present study. GH deficiency was defined as a peak serum concentration of GH less than 5 ng/mL in response to reevaluation with clonidine stimulation (75 mg/m2). The study was a double blind, placebo-controlled cross-over trial. After baseline examinations the patients were randomly allocated to 4 months of treatment with either hGH (Norditropin, Novo-Nordisk A/S, Copenhagen, Denmark; 2 IU/m2 body surface given sc daily at 2000 h) or placebo. To avoid any carryover effects a period of 4 months elapsed before cross-over took place. Examinations were performed at baseline and after each 4-month treatment period.
Received October 20,1989. Address all correspondence and requests for reprints to: Julia Sidenius Johansen, Department of Clinical Chemistry, Glostrup Hospital, DK-2600 Glostrup, Denmark. * This work was supported by grants from the Ib Henriksens Fond.
Patients with acromegaly Seven men and two women, aged 21-73 yr, were studied. Acromegaly was diagnosed on typical clinical presentation and 916
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 21 November 2015. at 14:15 For personal use only. No other uses without permission. . All rights reserved.
PLASMA BGP IN GH-DEFICIENT ADULTS elevated serum concentrations of GH, which were not suppressed during oral glucose load. High resolution computerized tomography confirmed pituitary tumor in each patient. None of the patients had kidney or liver disease. Blood samples were taken immediately before and 1 week after surgery. In all patients blood samples were taken and urine collected in the morning after an overnight fast. All samples were stored at —20 °C until analyzed. Plasma/serum BGP was determined by RIA (14). Antiserum was raised in rabbits immunized with purified intact calf BGP, BGP z score
64O 2 - - —CT 0 QO -2-h- _OP_
• _AA_ AAA
NS
p
