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Biological half-life of parathyroid hormone in the circulation
59
Abstracts From the Bone & Tooth Society had minor nonspecific symptoms only. In none of the patients, including those who died, was there evidence of progressive impairment of renal function. None of the patients developed acute hypercalcemia, and none had symptoms due to osteopenia.
BIOLOGIBALHALF-LIFE OF PARATHYf?OlDHORMONEIN THE CIRCUIATION J. Allgrove’ and J.L.H. O’Riordar? ‘Division of Cellular Biology, Mathilda & Terence Kennedy institute of Rheumatology, London W6 and 2Department of Medicine, Middlesex Hospital Medical School, London Wl, UK The half-life of parathyroid hormone (PTH) in the circulation, measured by immunoassays, has been considered to be short (c 3 min). The development of the cytochemical bioassay for PTH has allowed the measurement of the half-life of biologically active PTH (bio-PTH) for comparison. This study aimed to measure the half-life of endogenous bio-PTH in three patients. Changes in bio-PTH were assessed in two patients immediately following parathyroidectomy for primary parathyroidism due to a single adenoma and in one patient with malabsorptive hypomagnesaemia following intravenous injection of magnesium. All of the patients had normal renal function. In each of the two patients following parathyroidectcmy bio-PTH fell from 130 pglml and 454 pglml (NR 1-6 pglml), respectively, and became < 1 pg/ml within 10 min. Lo~,~ bio-PTH fell in a linear manner with time indicating a single half-life of 75 and 72 set, respectively. In the third patient, following injection of magnesium, bio-PTH first rose from 0.44 pg/ml to 96 pg/ml 5 min later, then fell with a single half-life of 56 set and became < 1 pglml after a further 7 min. These values for the half-life of bioPTH are similar to but slightly shorter than the shortest previously reported half-life of immunoreactive PTH. Although the conditions under which the half-life has been studied were not physiologic, the mean value (1.13 min) of the three subjects studied, combined with an estimated rate of secretion of PTH of 0.05 pglkglhr, predicts a plasma concentration of 2.7 pglml in normal subjects-well within the normal range for PTH fcund by cytochemical bioassay.
A STUOY OF IN VITRO RESORPTIONOF BONEBY HUMAN OSTEBCLABTSUS1110 MICRORADIOGRAPHY IN CONJUNCTION WITH SCANNING ELECTRON MICROSCOPY
J.A.S. Pringle,’ M.E.A. Brown,’ M.J. Wilkinson2 TJ. Chambers3 and K. Fuller3 Departments of ‘Morbid Anatomy and 2Biomedical Engineering, institute of Orthopaedics, and 3Department of Histopathology, St. Bartholomew’s Hospital, London, UK Microradiography, a technique already employed in the Department of Morbid Anatomy, institute of Orthopaedics in the study of metabolic bone disease, has been used in conjunction with SEM to detect and assess the pattern and amount of in vitro bone resorption by human osteoclasts and the relationship of these cells to the resorption pits. Slices of human cortical bone 30-50 ~1thick were cut on an lsomet saw using a diamond wafering blade. Microradiographs of these slices were taken prior to incubation with osteoclasts, and the natural bone features, namely, vascular channels and osteocyte lacunae, were clearly identified. Human osteoclasts were harvested from osteoclastcma tissue, settled on the bone slides,
and incubated for varying periods as previously described. The slices were fixed and the cells removed with triton. A second microradiograph of each slice was then taken and areas of resorption could be clearly seen. The bona slices were coated with gold paladium, and SEM was used to confirm the resorption seen by microradiography coincided with pits seen on SEM. Further studies were carried out in which bone slices were fixed following incubation with osteoclasts and the cells were not removed. A study was made of the relationship of osteoclasts seen on SEM with the pits seen by microradiography. This technique facilitates the study of early resorption, where the osteoclast is still sitting over its first pit obscuring it from view. (1)
Meteb.Bone 0s.
Rd. Res. (in
press).
CONSIDERATIONS WHEN MEASURING SERUM OSTEOCALCIN M. Couch,’ D.A. Woods,’ J.A. Gallagher,’ C.J. Preston,’ L.A. Coulton,’ R.G.G. Russell,’ J.A. Kanis,’ I.R. Dickson2 and J.W. Pose? ‘Department of Human Metabolism & Clinical Biochemistry, University of Sheffield Medical School, Beech Hill Road, Sheffield, 2Department of Medicine, New Addenbrooke’s Hospital, Cambridge, UK and 3The Procter & Gamble Company, USA We have been investigating osteocalcin as a marker of bone metabolism by measuring its concentration in serum by RIA. Our findings have shown that important considerations must be made before interpreting results. Osteocalcin measurements were made on sera from I94 normal subjects and were found to be log-normally distributed, with a mean value of 17.25 ng/ml (+ 2 SD 8.2-36.2 ng/ml). The mean value in males was 18.2 nglml (n = 108) and in females was 16.13 ng/ml (n = 86). A variation with age was seen, with high values in the first decade (15-25 yr) of our range (male 29.38, female 17.5 ng/ml), which tended to fall gradually until the last decade (55-64 yr) when the females showed an upturn (male 15.34, female 19.54 from 14.62 nglml in previcus decade). A group of 7 normal volunteers had blood taken at 4-hourly intervals for a day to investigate diurnal variation in serum osteocalcin. A variation was seen with a minimum mean value of 25.24 ng/ml in the afternoon, rising to a peak of 34.5 nglml nocturnally. A biannual variation in osteocalcin was seen in 30 normals, blood taken at 3-monthly intervals (Sept 19.3, Dee 24.3, Mar 19.6, June 28.1 nglml resp). One further variation that we have found has been in patients during pretreatment assessment. Even when blood was taken at a regular time of day from fasted subjects, daily variations of greater than 100% were observed in serum osteocalcin levels. We have demonstrated, therefore, variation in serum osteocalcin concentration with sex, age, time of day, time of year and with an unknown effect of disease. These five variations should be taken into account by groups studying serum osteocalcin.
EFFECT OF OVARIAN FUNCTION COMPARED TO AGE ON CALCITONIN SECRETION IN WOMEN M.I. Whitehead,’ G. Lane,’ M. Padwick,’ J.A. Endacott,’ C.H. Myers,2 and J.C. Stevenson2 ‘Academic Department of Obstetrics and Gynaecology, King’s College Hospital, London and 2Endocrine Unit, Royal Postgraduate Medical School,
Abstracts From the Bone & Tooth Society had minor nonspecific symptoms only. In none of the patients, including those who died, was there evidence of progressive impairment of renal function. None of the patients developed acute hypercalcemia, and none had symptoms due to osteopenia.
BIOLOGIBALHALF-LIFE OF PARATHYf?OlDHORMONEIN THE CIRCUIATION J. Allgrove’ and J.L.H. O’Riordar? ‘Division of Cellular Biology, Mathilda & Terence Kennedy institute of Rheumatology, London W6 and 2Department of Medicine, Middlesex Hospital Medical School, London Wl, UK The half-life of parathyroid hormone (PTH) in the circulation, measured by immunoassays, has been considered to be short (c 3 min). The development of the cytochemical bioassay for PTH has allowed the measurement of the half-life of biologically active PTH (bio-PTH) for comparison. This study aimed to measure the half-life of endogenous bio-PTH in three patients. Changes in bio-PTH were assessed in two patients immediately following parathyroidectomy for primary parathyroidism due to a single adenoma and in one patient with malabsorptive hypomagnesaemia following intravenous injection of magnesium. All of the patients had normal renal function. In each of the two patients following parathyroidectcmy bio-PTH fell from 130 pglml and 454 pglml (NR 1-6 pglml), respectively, and became < 1 pg/ml within 10 min. Lo~,~ bio-PTH fell in a linear manner with time indicating a single half-life of 75 and 72 set, respectively. In the third patient, following injection of magnesium, bio-PTH first rose from 0.44 pg/ml to 96 pg/ml 5 min later, then fell with a single half-life of 56 set and became < 1 pglml after a further 7 min. These values for the half-life of bioPTH are similar to but slightly shorter than the shortest previously reported half-life of immunoreactive PTH. Although the conditions under which the half-life has been studied were not physiologic, the mean value (1.13 min) of the three subjects studied, combined with an estimated rate of secretion of PTH of 0.05 pglkglhr, predicts a plasma concentration of 2.7 pglml in normal subjects-well within the normal range for PTH fcund by cytochemical bioassay.
A STUOY OF IN VITRO RESORPTIONOF BONEBY HUMAN OSTEBCLABTSUS1110 MICRORADIOGRAPHY IN CONJUNCTION WITH SCANNING ELECTRON MICROSCOPY
J.A.S. Pringle,’ M.E.A. Brown,’ M.J. Wilkinson2 TJ. Chambers3 and K. Fuller3 Departments of ‘Morbid Anatomy and 2Biomedical Engineering, institute of Orthopaedics, and 3Department of Histopathology, St. Bartholomew’s Hospital, London, UK Microradiography, a technique already employed in the Department of Morbid Anatomy, institute of Orthopaedics in the study of metabolic bone disease, has been used in conjunction with SEM to detect and assess the pattern and amount of in vitro bone resorption by human osteoclasts and the relationship of these cells to the resorption pits. Slices of human cortical bone 30-50 ~1thick were cut on an lsomet saw using a diamond wafering blade. Microradiographs of these slices were taken prior to incubation with osteoclasts, and the natural bone features, namely, vascular channels and osteocyte lacunae, were clearly identified. Human osteoclasts were harvested from osteoclastcma tissue, settled on the bone slides,
and incubated for varying periods as previously described. The slices were fixed and the cells removed with triton. A second microradiograph of each slice was then taken and areas of resorption could be clearly seen. The bona slices were coated with gold paladium, and SEM was used to confirm the resorption seen by microradiography coincided with pits seen on SEM. Further studies were carried out in which bone slices were fixed following incubation with osteoclasts and the cells were not removed. A study was made of the relationship of osteoclasts seen on SEM with the pits seen by microradiography. This technique facilitates the study of early resorption, where the osteoclast is still sitting over its first pit obscuring it from view. (1)
Meteb.Bone 0s.
Rd. Res. (in
press).
CONSIDERATIONS WHEN MEASURING SERUM OSTEOCALCIN M. Couch,’ D.A. Woods,’ J.A. Gallagher,’ C.J. Preston,’ L.A. Coulton,’ R.G.G. Russell,’ J.A. Kanis,’ I.R. Dickson2 and J.W. Pose? ‘Department of Human Metabolism & Clinical Biochemistry, University of Sheffield Medical School, Beech Hill Road, Sheffield, 2Department of Medicine, New Addenbrooke’s Hospital, Cambridge, UK and 3The Procter & Gamble Company, USA We have been investigating osteocalcin as a marker of bone metabolism by measuring its concentration in serum by RIA. Our findings have shown that important considerations must be made before interpreting results. Osteocalcin measurements were made on sera from I94 normal subjects and were found to be log-normally distributed, with a mean value of 17.25 ng/ml (+ 2 SD 8.2-36.2 ng/ml). The mean value in males was 18.2 nglml (n = 108) and in females was 16.13 ng/ml (n = 86). A variation with age was seen, with high values in the first decade (15-25 yr) of our range (male 29.38, female 17.5 ng/ml), which tended to fall gradually until the last decade (55-64 yr) when the females showed an upturn (male 15.34, female 19.54 from 14.62 nglml in previcus decade). A group of 7 normal volunteers had blood taken at 4-hourly intervals for a day to investigate diurnal variation in serum osteocalcin. A variation was seen with a minimum mean value of 25.24 ng/ml in the afternoon, rising to a peak of 34.5 nglml nocturnally. A biannual variation in osteocalcin was seen in 30 normals, blood taken at 3-monthly intervals (Sept 19.3, Dee 24.3, Mar 19.6, June 28.1 nglml resp). One further variation that we have found has been in patients during pretreatment assessment. Even when blood was taken at a regular time of day from fasted subjects, daily variations of greater than 100% were observed in serum osteocalcin levels. We have demonstrated, therefore, variation in serum osteocalcin concentration with sex, age, time of day, time of year and with an unknown effect of disease. These five variations should be taken into account by groups studying serum osteocalcin.
EFFECT OF OVARIAN FUNCTION COMPARED TO AGE ON CALCITONIN SECRETION IN WOMEN M.I. Whitehead,’ G. Lane,’ M. Padwick,’ J.A. Endacott,’ C.H. Myers,2 and J.C. Stevenson2 ‘Academic Department of Obstetrics and Gynaecology, King’s College Hospital, London and 2Endocrine Unit, Royal Postgraduate Medical School,