Summary
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 6 IU/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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ranke MB, Bierich JR (1986) Treatment of growth hormone deficiency. Clin Endocrinol Metab 15:495–510
Hintz RL, Rosenfeld RG, Wilson DM, Bennett A, Finno J, McClellen B, Swift R (1982) Biosynthetic methionyl human growth hormone is biologically active in adult man. Lancet i:1276–1279
Jørgensen JOL, Flyvbjerg A, Lauritzen T, Alberti KGMM, Ørskov H, Christiansen JS (1987) Dose-response studies with biosynthetic human growth hormone (GH) in GH-deficient patients. J Clin Endocrinol Metab 67:36–40
Valk IM, Langout Chabloz AME, Smals AGH, Kloppenborg PWC, Cassorla FG, Schutte EAST (1983) Accurate measurement of the lower leg length and the ulnar length and its application in short-term growth measurement. Growth 47:53–66
Schlecter NL, Russel SM, Spencer EM, Nicoll CS (1986) Evidence suggesting that the direct growth-promoting effect of hormone on cartilage in vivo is mediated by local production of somatomedin. Proc Natl Acad Sci USA 83:7932–7934
D'Ercole AJ, Stiles AD, Underwood LE (1984) Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 81:935–939
Rosenfeld RG, Kemp SF, Hintz RL (1981) Constancy of somatomedin response to growth hormone treatment of hypopituitary dwarfism and lack of correlation with growth rate. J Clin Endocrinol Metab 53:611–617
Price PA, Otsuka AS, Poser JW, Kristaponis J, Raman N (1976) Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci USA 73:1447–1451
Price PA, Nishimoto SK (1980) Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci USA 77:2234–2238
Charles P, Poser JW, Mosekilde L, Jensen FT (1985) Estimation of bone turnover evaluated by47Ca-kinetics. J Clin Invest 76:2254–2258
Delmas PD, Malaval L, Arlot ME, Menuier PJ (1985) Serum bone GLA-protein compared to bone histomorphometry in endocrine diseases. Bone 6:339–341
Melick RA, Farrugia W, Heaton CL, Quelch KJ, Scoggins BA, Ward JD (1988) The metabolic clearance rate of osteocalcin in sheep. Calcif Tissue Int 42:185–190
Delmas PD, Chatelain P, Malaval L, Bonne G (1986) Serum bone GLA-protein in growth hormone deficient children. J Bone Min Res 4:333–338
Markowitz ME, Dimartino-Nardi J, Gasparini F, Fishman K, Rosen JF, Saenger P (1989) Effect of growth hormone therapy on circadian rhythm in idiopathic short stature. J Clin Endocrinol Metab 69:420–425
Rosalki SB, Foo AY (1984) Two new methods for separating and quantifying bone and liver alkaline phosphatase isoenzymes in plasma. Clin Chem 30:1182–1186
Behr W, Barnert J (1986) Quantification of bone alkaline phosphatase in serum by precipitation with wheat germ lectin: a simplified method and its clinical plausability. Clin Chem 32:1960–1966
Brixen K, Nielsen HK, Eriksen EF, Charles P, Mosekilde L (1989) Efficacy of wheat germ lectin-precipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: comparison to serum total alkaline phosphatase and serum bone GLA-protein. Calcif Tissue Int 44:93–98
Spiess YH, Price PA, Deftos JL, Manolagas (1986) Phenotype-associated changes in the effects of 1,25-dihydroxyvitamin D3 on alkaline phosphatase and bone Gla protein of rat osteoblastic cells. Endocrinology 118:1340–1346
Johansen JS, Giwercman A, Hartwell D, Nielsen CT, Price PA, Christiansen C, Skakkebæk NE (1988) Serum bone GLA-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor I, and serum testosterone. J Clin Endocrinol Metab 67:273–278
Round JM (1973) Plasma calcium, magnesium, phosphorus, and alkaline phosphatase levels in normal British schoolchildren. Br Med J 3:137–140
Christensen SE, Jørgensen JOL, Møller N, Ørskov H (1984) Characterization of growth hormone in response to external heating: comparison to exercise-induced release. Acta Endocrinol (Copenh) 107:295–301
Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity and weight velocity and the stages of puberty. Arch Dis Child 51:170–179
Keiding R, Hörder M, Gerhardt W, Pitkänen E, Tenhunen R, Strömme JH, Theodorsen L, Waldenström J, Tryding N, Westlund L (1974) Recommended method for the determination of four enzymes in blood. Scand J Clin Lab Invest 33:291–306
Kastrup KW, Sandahl-Christensen J, Koch Andersen I, Ørskov H (1983) Increased growth rate following transfer to daily s.c. administration from three weekly i.m. injections of hGH in growth hormone-deficient children. Acta Endocrinol 104:148–152
Delmas PD, Wilson DM, Mann KG, Riggs LB (1983) Effects of renal function on plasma levels of GLA-protein. J Clin Endocrinol Metab 57:1028–1030
Corvilain J, Abramow M, Bergans A (1962) Some effects of human growth hormone on renal hemodynamics and on tubular phosphate transport in man. J Clin Invest 41:1230–1235
Christiansen JS, Gammelgaard J, Ørskov H, Andersen AR, Telmer S, Parving HH (1981) Kidney function and size in normal subjects before and during growth hormone administration for one week. Eur J Clin Invest 11:487–490
Walton RJ, Preston CJ, Russell RGG, Kanis JA (1975) An estimate of the turnover rate of bone-derived plasma alkaline phosphatase in Paget's disease. Clin Chim Acta 63:227–229
Thavarajah M, Evans DB, Russell RGG, Kanis JA (1985) Immunocytochemical demonstration of osteocalcin in human bone-derived cells (abstract). First Intl Symp on Cells and Cytokines in Bone and Cartilage, Davos, Switzerland
Gundberg CM, Markowitz ME, Mizruchi M, Rosen JF (1985) Osteocalcin in human serum: a circadian rhythm. J Clin Endocrinol Metab 60:736–739
Markowitz ME, Gundberg CM, Rosen JF (1987) The circadian rhythm of serum osteocalcin concentrations: effects of 1,25 dihydroxyvitamin D administration. Calcif Tissue Int 40:179–183
Nielsen HK, Charles P, Mosekilde L (1988) The effect of single oral doses of prednisone on the circadian rhythm of serum osteocalcin in normal subjects. J Clin Endocrinol Metab 67:1025–1029
Thomsen K, Eriksen EF, Jørgensen JCR, Charles P, Mosekilde L (1989) Seasonal variation of serum bone GLA-protein. Scand J Clin Lab Invest 49:605–611
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nielsen, H.K., Jørgensen, J.O.L., Brixen, K. et al. Serum osteocalcin and bone isoenzyme alkaline phosphatase in growth hormone-deficient patients: Dose-response studies with biosynthetic human GH. Calcif Tissue Int 48, 82–87 (1991). https://doi.org/10.1007/BF02555871
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02555871