scholarly journals Effect of Active Acromegaly and Its Treatment on Parathyroid Circadian Rhythmicity and Parathyroid Target-Organ Sensitivity

2006 ◽  
Vol 91 (3) ◽  
pp. 913-919 ◽  
Author(s):  
H. D. White ◽  
A. M. Ahmad ◽  
B. H. Durham ◽  
S. Chandran ◽  
A. Patwala ◽  
...  
Keyword(s):  
Reference Range ◽  
Target Organ ◽  
Oral Glucose ◽  
Type I ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Igf I ◽  
Procollagen Type I ◽  
Biochemical Cure ◽  
Active Acromegaly

Abstract Context: Patients with active acromegaly have increased bone turnover and skeletal abnormalities. Biochemical cure of acromegaly may represent a functional GH-deficient state and result in cortical bone loss. Reduced PTH target-organ sensitivity occurs in adult GH deficiency and may underlie the associated development of osteoporosis. Objective: We examined the effect of active and treated acromegaly on PTH concentration and target-organ sensitivity. Patients: Ten active acromegalic subjects (GH nadir > 0.3 μg/liter after 75-g oral glucose load and IGF-I above age-related reference range) and 10 matched controls participated in the study. Design: Half-hourly blood and 3-h urine samples were collected on patients and controls for 24 h. Samples were analyzed for PTH, calcium (Ca), nephrogenous cAMP (NcAMP, a marker of PTH renal activity), β C-telopeptide (bone resorption marker), and procollagen type-I amino-terminal propeptide (bone formation marker). Serum calcium was adjusted for albumin (ACa). Eight acromegalic subjects who achieved biochemical cure (GH nadir < 0.3 μg/liter after 75-g oral glucose load and IGF-I within reference range) after standard surgical and/or medical treatment reattended and the protocol repeated. Results: Active acromegalic subjects had higher 24-h mean PTH, NcAMP, ACa, urine Ca, β C-telopeptide, and procollagen type I amino-terminal propeptide (P < 0.05), compared with controls. Twenty-four-hour mean PTH increased (P < 0.001) in the acromegalic subjects after treatment, whereas NcAMP and ACa decreased (P < 0.05). Conclusion: Increased bone turnover associated with active acromegaly may result from increased PTH concentration and action. Biochemical cure of acromegaly results in reduced PTH target-organ sensitivity indicated by increased PTH with decreased NcAMP and ACa concentrations. PTH target-organ sensitivity does not appear to return to normal after successful treatment of acromegaly in the short term and may reflect functional GH deficiency.

Purification of human procollagen type I carboxyl-terminal propeptide cleaved as in vivo from procollagen and used to calibrate a radioimmunoassay of the propeptide

1994 ◽  
Vol 40 (5) ◽  
pp. 811-816 ◽  
Author(s):  
B J Pedersen ◽  
M Bonde
Keyword(s):  
Geometric Mean ◽  
Sodium Dodecyl ◽  
Gel Filtration ◽  
Type I ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Fetal Fibroblasts ◽  
Procollagen Type I ◽  
Carboxyl Terminal

Abstract We purified human procollagen type I carboxyl-terminal propeptide (PICP) that had been cleaved as in vivo from procollagen. PICP in serum-free medium from cultured human fetal fibroblasts was purified by thiophilic adsorption chromatography, low-pressure gel filtration, and HPLC gel filtration. The purity and homogeneity of the protein was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino-terminal amino acid sequencing showed that the sequences of the alpha 1 and alpha 2 chains of this PICP were identical to those of the PICP produced in vivo. The monocomponent PICP thus purified was used as calibrator in a simple equilibrium-type RIA of PICP with polyclonal antibodies raised in rabbits. The measuring range is 0.15-3.75 nmol/L, and the assay detection limit is 0.03 nmol/L. The within-run and total CVs are 2% and 4%, respectively. The reference interval for the plasma concentration of PICP in healthy women of ages > 30 years is 0.36-1.44 nmol/L (geometric mean 0.72 nmol/L, n = 154).

scholarly journals Acute Changes of Bone Turnover and PTH Induced by Insulin and Glucose: Euglycemic and Hypoglycemic Hyperinsulinemic Clamp Studies

2002 ◽  
Vol 87 (7) ◽  
pp. 3324-3329 ◽  
Author(s):  
Jackie A. Clowes ◽  
Robert T. Robinson ◽  
Simon R. Heller ◽  
Richard Eastell ◽  
Aubrey Blumsohn
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Oral Glucose ◽  
Type I ◽  
Double Blind ◽  
Euglycemic Clamp ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Significant Change ◽  
Acute Changes

Bone turnover is acutely suppressed after feeding or oral glucose. Insulin infusion suppresses bone turnover and might mediate this effect, but this is confounded by a possible direct effect of hypoglycemia. We examined the effect of euglycemic hyperinsulinemia and hypoglycemic hyperinsulinemia on bone turnover using an insulin clamp. Sixteen men participated in this double-blind crossover study. Clamp induction involved infusion of insulin (80 mU/m2·min) while maintaining euglycemia (5 mmol/liter) for 40 min with a variable rate dextrose infusion. Glucose was lowered to 2.5 mmol/liter (hypoglycemic clamp) or maintained at 5 mmol/liter (euglycemic clamp) for a further 105 min. Nine controls received a matched saline infusion. Measurements included serum C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide, osteocalcin, and PTH. Induction of hyperinsulinemia resulted in a reduction in PTH (27% ± 5; P < 0.01), but no significant change in bone turnover from baseline. Hypoglycemic clamp resulted in suppression of serum C-terminal telopeptide of type I collagen by 34% ± 3, procollagen type I N-terminal propeptide by 15% ± 1, osteocalcin by 5% ± 1, and PTH by a further 12% ± 5 (all P < 0.05). By contrast, there was no significant change in any marker of bone turnover during euglycemic clamp. Postprandial hyperinsulinemia is unlikely to explain the acute suppression of bone turnover with feeding. The reduction in bone turnover during hypoglycemia may be related to hypoglycemia itself, acute changes in PTH, or other hormones released in response to hypoglycemia.

scholarly journals Octreotide Abolishes the Acute Decrease in Bone Turnover in Response to Oral Glucose

2003 ◽  
Vol 88 (10) ◽  
pp. 4867-4873 ◽  
Author(s):  
Jackie A. Clowes ◽  
Heather C. Allen ◽  
Donna M. Prentis ◽  
Richard Eastell ◽  
Aubrey Blumsohn
Keyword(s):  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Gastrointestinal Hormones ◽  
Oral Glucose ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Turnover Markers

Abstract Feeding or oral intake of glucose results in an acute suppression of bone turnover. This does not appear to be mediated by insulin. Several gastrointestinal hormones modulate bone turnover in vitro and may mediate this response. We examined whether inhibiting the production of gastrointestinal hormones using octreotide could block glucose-mediated suppression of bone turnover. Fifteen subjects were each studied on four occasions in a randomized, single-blind, crossover study after receiving 1) oral placebo, iv saline; 2) oral glucose, iv saline; 3) oral glucose, iv octreotide; or 4) iv octreotide alone. We measured serum C-terminal telopeptide of type I collagen, urinary N-terminal telopeptide of type I collagen, osteocalcin, procollagen type I N-terminal propeptide, PTH, insulin, ionized calcium, and glucose over 4 h. All bone turnover markers decreased significantly after oral glucose (P < 0.001). At 120 min serum C-terminal telopeptide decreased by 45 ± 2%, urinary N-terminal telopeptide by 31 ± 7%, osteocalcin by 16 ± 1%, and procollagen type I N-terminal propeptide by 8 ± 1%. There was no significant decrease in bone turnover in response to oral glucose during octreotide infusion. Octreotide alone resulted in a significant increase in all bone turnover markers (P < 0.05) and PTH (P < 0.01). We conclude that octreotide completely abolishes the bone turnover response to glucose intake and increases PTH secretion. The apparent bone turnover response to feeding is probably mediated by an octreotide-inhibitable endocrine factor.

scholarly journals A Monoclonal Antibody Specific for the Amino Terminal Cleavage Site of Procollagen Type I

1983 ◽  
Vol 134 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Harald G. FOELLMER ◽  
Kazuko KAWAHARA ◽  
Joseph A. MADRI ◽  
Heinz FURTHMAYR ◽  
Rupert TIMPL ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cleavage Site ◽  
Type I ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Procollagen Type I

scholarly journals Procollagen Type I Amino-Terminal Propeptide: Pediatric Reference Data and Relationship with Procollagen Type I Carboxyl-Terminal Propeptide

2004 ◽  
Vol 50 (11) ◽  
pp. 2173-2176 ◽  
Author(s):  
Patricia M Crofton ◽  
Nancy Evans ◽  
Mervyn R H Taylor ◽  
Celia V Holland
Keyword(s):  
Reference Data ◽  
Type I ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Procollagen Type I ◽  
Carboxyl Terminal

scholarly journals Pegvisomant-Induced Serum Insulin-Like Growth Factor-I Normalization in Patients with Acromegaly Returns Elevated Markers of Bone Turnover to Normal

2003 ◽  
Vol 88 (12) ◽  
pp. 5650-5655 ◽  
Author(s):  
C. Parkinson ◽  
M. Kassem ◽  
L. Heickendorff ◽  
A. Flyvbjerg ◽  
P. J. Trainer
Keyword(s):  
Vitamin D ◽  
Soft Tissue ◽  
Type I ◽  
Amino Terminal ◽  
Type I Procollagen ◽  
Markers Of Bone Turnover ◽  
Igf I ◽  
Tissue Turnover ◽  
25 Hydroxy Vitamin D ◽  
Active Acromegaly

Abstract Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28–78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)2 vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 ± 76 to 242 ± 28 μg/liter, P < 0.001) was associated with a significant decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)2 vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated positively with the decrease of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there was no statistical difference between patients and controls for any parameters for which control data were available. In conclusion, GH excess is associated with increased bone and soft tissue turnover. Pegvisomant-induced normalization of serum IGF-I results in a decrease in markers of bone and soft tissue turnover to levels observed in age-matched controls, and these changes are accompanied by an increase in PTH and a decrease in 1,25-(OH)2 vit D. These data provide further evidence of the effectiveness of pegvisomant in normalizing the altered biological effects of GH hypersecretion.

scholarly journals Osteokines and Bone Markers at Rest and following Plyometric Exercise in Pre- and Postmenopausal Women

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Katlynne Nelson ◽  
Rozalia Kouvelioti ◽  
Alexandros Theocharidis ◽  
Bareket Falk ◽  
Peter Tiidus ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Type I Collagen ◽  
Premenopausal Women ◽  
Type I ◽  
Bone Homeostasis ◽  
Younger Women ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Plyometric Exercise ◽  
Procollagen Type I

The effect of plyometric exercise on bone biomarkers has been studied in pediatric and young adult populations in order to better understand how exercise influences bone homeostasis. However, there are no such data in postmenopausal women, a group characterized by an uncoupling of the bone resorption-formation cycle. This study examined the serum concentrations of sclerostin, dickkopf-1 (DKK1), c-terminal crosslinking telopeptides of type I collagen (CTXI), and procollagen type I amino-terminal propeptide (PINP) at rest and following a single bout of plyometric exercise in 20 premenopausal ( 23.1 ± 2.3 years) and 20 postmenopausal women ( 57.9 ± 4.3 years). The exercise consisted of 128 jumps, organized into 5 circuit stations. Blood samples were obtained prior to and 5 min, 1 h, and 24 h postexercise. At rest, postmenopausal women had significantly higher sclerostin and CTXI, but lower DKK1 than premenopausal women. Sclerostin increased 5 min postexercise only in the premenopausal group. DKK1 decreased 24 h postexercise in the premenopausal women while it decreased 1 h postexercise in the postmenopausal women. In both groups, CTXI did not change across time and PINP decreased 5 min and 1 h postexercise ( p < 0.05 ). The PINP/CTXI ratio decreased 5 min and 1 h postexercise then significantly increased 24 h postexercise only in premenopausal women. These results indicate that although plyometric exercise is effective in eliciting osteoanabolic effects in younger women; such an effect is not evident in postmenopausal women.

Abstract 74: The Inflammatory Phenotype Of Mesenchymal Fibroblasts And Its Role In Aging Dependent Cardiac Fibrosis- A Target For Statins?

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Katarzyna A Cieslik ◽  
JoAnn Trial ◽  
Mark L Entman
Keyword(s):  
Endothelial Cells ◽  
Myeloid Cell ◽  
Transendothelial Migration ◽  
Mouse Heart ◽  
Type I ◽  
Aged Mouse ◽  
Vitro Assay ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Inflammatory Phenotype

In the aging mouse (C57BL/6) myocardium fibrosis steadily increases after 14 months of age and is accompanied by elevated numbers of myeloid derived fibroblasts. Recently, we proposed a mechanism by which inflammatory mesenchymal fibroblasts (IMF) derived from mesenchymal stem cells secrete monocyte chemoattractant protein-1 (MCP-1) necessary for myeloid fibroblast induction in the aging heart. The current study extends the characterization of this inflammatory phenotype by describing elevated interleukin-6 (IL-6) secretion and increased expression of IL-6 receptor (IL-6R) in IMF. Since IL-6R lacks an intracellular domain it requires a co-receptor gp130 (generally expressed) to induce an intracellular signal. Thus, generation of an IL-6R soluble receptor allows IL-6 signaling on cells that do not express IL-6R (or expression is low), such as endothelial cells. We investigate the function of IL-6 and IL-6R in the promotion of transendothelial migration of monocytes through cardiac endothelium and their maturation into myeloid fibroblasts in in vitro assay. Treatments with IL-6 and more extensively IL-6+IL-6R resulted in a 3-5 fold increase (above the control level) in myeloid cell migration and maturation into myeloid fibroblasts. Thus IMF can contribute both IL-6 and IL-6R to endothelial cells and facilitate myeloid cell transendothelial migration. In agreement with these data, analysis of the aged mouse heart revealed the presence of fibroblasts expressing IL-6 (procollagen type I + IL-6 + cells), M1 macrophages (CD86 + cells) and M2 macrophages (CD301 + procollagen type I + cells) that were absent in hearts from young mice. The mechanisms by which expression of these factors is upregulated in IMF are being investigated; our data suggest that MCP-1 and IL-6 expression are controlled by the farnesyltransferase (FTase)-Ras-Erk1/2 pathway. Interestingly, since atorvastatin interferes with farnesyl synthesis it also reduced MCP-1 and IL-6 expression in IMF. These data may introduce a new use of this class of drugs in the prevention of the age-related fibrosis.

Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts

1994 ◽  
Vol 130 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Moustapha Kassem ◽  
Leif Mosekilde ◽  
Erik F Eriksen
Keyword(s):  
Bone Marrow ◽  
Alkaline Phosphatase ◽  
Sodium Fluoride ◽  
Bone Cells ◽  
Human Bone ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Osteoblast Precursors

Kassem M, Mosekilde L, Eriksen EF. Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts. Eur J Endocrinol 1994;130:381–6. ISSN 0804–4643 The cellular effects of sodium fluoride (NaF) on human bone cells in vitro have been variable and dependent on the culture system used. Variability could be attributed to differences in responsiveness to NaF among different populations of cells at various stages of differentiation in the osteoblastic lineage. In this study we compared the effects of NaF in serum-free medium on cultures of more differentiated human osteoblast-like (hOB) cells derived from trabecular bone explants and on osteoblast committed precursors derived from human bone marrow, i.e. human marrow stromal osteoblast-like (hMS(OB)) cells. Sodium fluoride (10−5 mol/l) increased proliferation of hMS(OB) cells (p<0.05, N = 10) but was not mitogenic to hOB cells (p>0.05, N= 10). Alkaline phosphatase (AP) production increased in both hMS(OB) (p<0.05, N=9) and hOB cells (p<0.05, N=9). No significant effects on procollagen type I propeptide production were obtained in either culture. In the presence of 1,25-dihydroxycholecalciferol (10−9 mol/l), NaF enhanced alkaline phosphatase (p<0.05, N=8), procollagen type I propeptide (p<0.05, N=7) and osteocalcin (p<0.05, N=7) production by hMS(OB) cells but not by hOB cells. Our results suggest that osteoblast precursors are more sensitive to NaF action than mature osteoblasts and that the in vivo effects of NaF on bone formation may be mediated by stimulating proliferation and differentiation of committed osteoblast precursors in bone marrow. M Kassem, Mayo Clinic, Endocrine Research Unit, W-Joseph 5-164, Rochester, MN 55904, USA

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