scholarly journals The effect of timing of teriparatide treatment on the circadian rhythm of bone turnover in postmenopausal osteoporosis

2011 ◽  
Vol 164 (4) ◽  
pp. 643-648 ◽  
Author(s):  
Maria Luchavova ◽  
Vit Zikan ◽  
Dana Michalska ◽  
Ivan Raska ◽  
Ales A Kubena ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Bone Turnover ◽  
Collagen Type I ◽  
Time Of Day ◽  
Repeated Measurements ◽  
Type I ◽  
Procollagen Type ◽  
Teriparatide Treatment ◽  
Procollagen Type I ◽  
Turnover Markers

BackgroundWe hypothesized that with the administration of teriparatide (TPTD) treatment at different times, we would be able to modify the physiological circadian rhythm of bone turnover.MethodsThe concentration of serum C-terminal telopeptide of collagen type I (βCTX), serum N-terminal propeptide of procollagen type I (P1NP), serum ionized calcium (iCa), and plasma PTH were measured every 3 h over a 24 h period in 14 postmenopausal osteoporotic women (aged 72.4±9.3 years) treated with 20 μg TPTD for long term, given at different times of the day. General linear model-repeated measurements (GLM RM) were performed to analyze the circadian rhythms as well as intergroup comparisons.ResultsGLM-RM for both related groups showed a significant influence of time of day on all measured variables except P1NP. The analysis for each group separately provided a powerful model for βCTX (P<0.001, η2=0.496), serum iCa (P<0.001, η2=0.423), plasma PTH (P<0.001, η2=0.283), and serum PINP (P<0.001, η2=0.248). While the evening TPTD treatment showed a marked circadian rhythm for serum βCTX, the morning TPTD treatment rather suggested circasemidian rhythm. The P1NP rhythm followed a much smaller amplitude of the rhythm than βCTX. Changes in serum iCa were positively related to changes in serum βCTX (P<0.001) and negatively related to changes in PTH (P<0.001).ConclusionTiming of TPTD administration may significantly change the 24 h variation in bone turnover markers as well as calcium-parathyroid axis in postmenopausal osteoporotic women.

scholarly journals The effects of discontinuing long term alendronate therapy in a clinical practice setting

2011 ◽  
Vol 55 (4) ◽  
pp. 272-278 ◽  
Author(s):  
André Gonçalves da Silva ◽  
José Gilberto H. Vieira ◽  
Ilda Sizue Kunii ◽  
Janaína Martins de Lana ◽  
Marise Lazaretti-Castro
Keyword(s):  
Bone Turnover ◽  
Collagen Type I ◽  
Type I ◽  
Mineral Density ◽  
Procollagen Type ◽  
Post Menopausal Osteoporosis ◽  
Treatment Naïve ◽  
Turnover Markers ◽  
Group 2 ◽  
Post Menopausal

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7%) in G1 and one (5.2%) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

scholarly journals Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women

2014 ◽  
Vol 112 (10) ◽  
pp. 1611-1620 ◽  
Author(s):  
Sarah M. Bristow ◽  
Greg D. Gamble ◽  
Angela Stewart ◽  
Lauren Horne ◽  
Meaghan E. House ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Controlled Trial ◽  
Type I ◽  
Acute Effects ◽  
Procollagen Type ◽  
Equivalent Efficacy ◽  
Procollagen Type I ◽  
Phosphate Product ◽  
Turnover Markers ◽  
Randomised Controlled

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate–carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate–carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate–carbonate dose; however, it raised the concentrations of phosphate and the Ca–phosphate product. The citrate–carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

scholarly journals THU0262 LEVELS OF OSTEOCALCIN AND PROCOLLAGEN TYPE I C-TERMINAL PROPEPTIDE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS, THEIR ASSOCIATION WITH BONE MINERAL DENSITY AND LEVEL OF INTERLEUKIN-6

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 358.2-358
Author(s):  
S. Shevchuk ◽  
L. Denyshchych
Keyword(s):  
Bone Turnover ◽  
Bone Tissue ◽  
Lupus Erythematosus ◽  
Bone Turnover Markers ◽  
Type I ◽  
Z Score ◽  
Tissue Metabolism ◽  
Procollagen Type ◽  
Procollagen Type I ◽  
Turnover Markers

Background:Osteoporosis and fractures associated with it are considered to be one of the most severe complications of systemic lupus erythematosus (SLE). The role of a systemic inflammatory process, vitamin D deficiency, hypogonadism and peculiarities of disease treatment in reduced bone mineral density (BMD) is being discussed. Even though the frequency of osteoporosis in patients with SLE is being studied extensively by scientists from different countries, data on the peculiarities of bone tissue metabolism and the factors that provoke disorders of bone remodeling in such individuals are quite limited. The association between markers of bone tissue metabolism and BMD, and how they change during an inflammatory process is poorly studied.Objectives:The objective of our research is to study the levels of osteocalcin (OC) and procollagen type I C-terminal propeptide (PICP) in patients with systemic lupus erythematosus and to estimate their association with BMD and inflammatory activity based on the levels of interleukin-6 (IL-6).Methods:A total of 58 women with SLE (the average age was 45.11 ± 1.03 years old) and 29 individuals from the control group (the average age was 46.79 ± 2.30 years old) were examined. The diagnosis of SLE was established on the basis of 2019 EULAR/ACR classification criteria for SLE. Levels of IL-6, OC and PICP in serum were determined by enzyme immunoassay. Changes in BMD of the lumbar spine at the level of L1-L4 and the proximal femur were determined by dual-energy X-ray absorptiometry. In postmenopausal women, the diagnosis of osteoporosis was established by the T-score ≤ -2.5 SD. Osteopenia met T-score from -1 to -2.5 SD. In women of reproductive age, the Z-score was used to determine BMD. Values of the Z-score ≤ -2.0 SD were considered as “below expected range for age”.Results:The average OC level in serum of practically healthy individuals equaled 17.64 ± 0,59 ng/ml, and in patients with SLE it was 13.96 ± 0.40 ng/ml, i.e. it was 20.9% lower. The average PICP level in the control group equaled 107.8 ± 4.28 ng/ml, in the main group it was 92.9 ± 5.01 ng/ml, i.e. 16% lower. Overall, the decrease in the bone turnover markers (PICP and/or OC) was noticed in 28 patients with SLE (48.3%) and only in 4 practically healthy individuals (13.8%).In women with decreased bone turnover markers, the T-score of the lumbar spine and hip was 2.3-2.6 times lower (p < 0.05) than in the group with adequate levels of bone turnover markers. Z-score was also lower among patients with decreased levels of OC and PICP. In this group, the average BMD level was 0.81 ± 0.05 g/cm2and was 13.8% lower than in the group of patients with no signs of bone tissue metabolism disorder – 0.94 ± 0.02 g/cm2. Among the group of women with signs of suppression of biosynthetic processes in bone tissue, there were twice more individuals with decreased BMD. In patients with critically high levels of IL-6 (above 20.0 ng/L), OC level was lower than in patients with high (12.5-20.0 ng/L) and adequate (< 12.5 ng/L) levels of IL-6 (by 17.3 and 19% respectively). The proportion of individuals with low OC levels increased from 31.2% in the last group to 70.6% among patients with critically high levels of IL-6.PICP level was also lower (38.1% and 39.7% respectively) in case of critically high IL-6 levels compared to its high and adequate levels. The proportion of individuals with low PICP levels increased from 6.3% in the group with adequate IL-6 level to 58.8% in the group with critically high IL-6 level.Conclusion:Women with SLE have bone tissue metabolism disorder in the form of decreased bone turnover markers (procollagen type I C-terminal propeptide and osteocalcin) associated with the inflammatory activity. In the group of patients with the signs of suppression of biosynthetic processes in the bone tissue, there were more individuals with decreased BMD.Disclosure of Interests:Sergii Shevchuk Grant/research support from: Celltrion, Inc, Liudmyla Denyshchych: None declared

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 &lt; 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 &lt; 0.05) and PTH (P &lt; 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 Mutations in COL1A1 and COL1A2 Genes Associated with Osteogenesis Imperfecta (OI) Types I or III.

2018 ◽  
Vol 65 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Aleksandra Augusciak-Duma ◽  
Joanna Witecka ◽  
Aleksander L. Sieroń ◽  
Magdalena Janeczko ◽  
Jacek J Pietrzyk ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Collagen Type ◽  
Collagen Type I ◽  
Base Substitution ◽  
Type I ◽  
Intracellular Accumulation ◽  
Single Base ◽  
Type Iii ◽  
Procollagen Type ◽  
Procollagen Type I

Over 85% of osteogenesis imperfecta (OI) cases associates to mutations in procollagen type I genes (COL1A1 or COL1A2), however, no hot spots were linked to particular clinical phenotypes. The 8 patients whom were clinically diagnosed with OI are from Polish population with no ethnic background indicated. Six unpublished mutations were detected in eight patients diagnosed with OI. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were also determined. In COL1A1 gene the mutations were found in exons 2, 22, 50 and in introns 13 and 51. In COL1A2 one mutation was identified in exon 22. Mutations of deletion type in COL1A1 that resulted in OI type I an effect neither on collagen type I secretion nor its intracellular accumulation were detected. Also, a single base substitution in I13 (c.904-9 G>T) was associated with OI type I. The OI type III was associated with single base change in I51 of COL1A1, possibly causing an exon skipping. Also, a missense mutation in COL1A2 changing Gly®Cys in the central part of triple helical domain of the collagen type I molecule caused OI type III. It affected secretion of heterotrimeric form of procollagen type I. However, no intracellular accumulation of procollagen chains could be detected. Mutation in COL1A2 affected its incorporation to procollagen type I. The results shall help in genetic counseling of OI patients and provide rational support in making by them and their families conscious, life important decisions.

scholarly journals Collagen Turnover Markers in Relation to Future Cardiovascular and Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

2017 ◽  
Vol 63 (7) ◽  
pp. 1237-1247 ◽  
Author(s):  
Daniel A Duprez ◽  
Myron D Gross ◽  
Otto A Sanchez ◽  
Jorge R Kizer ◽  
Joachim H Ix ◽  
...  
Keyword(s):  
Good Health ◽  
International Classification Of Diseases ◽  
Collagen Type I ◽  
Type I ◽  
Ethnic Study ◽  
Procollagen Type ◽  
Relative Risks ◽  
Total Death ◽  
Turnover Markers ◽  
Remodeling Of Extracellular Matrix

Abstract BACKGROUND Sustained remodeling of extracellular matrix can compromise organs and tissues. Procollagen type III N-terminal propeptide (PIIINP) and collagen type I carboxy-terminal telopeptide (ICTP) reflect collagen synthesis and degradation. We studied their predictive value for future death and disease. METHODS A total of 3068 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken for ICTP and PIIINP. Median follow-up was 13.0 years. Among 4 primary outcomes, CVD events (n = 697) were adjudicated, death (n = 571) was by death certificate, and chronic inflammatory–related severe hospitalization and death (ChrIRD, n = 726) and total cancer (n = 327) were classified using International Classification of Diseases codes. We used Poisson regression to study baseline ICTP and PIIINP relative to these outcomes. RESULTS Mean (SD) PIIINP was 5.47 (1.95) μg/L and ICTP was 3.37 (1.70) μg/L. PIIINP and ICTP were highly correlated with each other and with estimated glomerular filtration rate (eGFR). Adjustment for age and eGFR attenuated relative risks, remaining 20%–30% per SD of both PIIINP and ICTP in prediction for total death and ChrIRD, and of PIIINP for cancer, with little additional attenuation by adjusting for risk factors and inflammatory biomarkers. CVD outcome was generally unrelated to PIIINP but became marginally inversely related to ICTP in the most adjusted model. CONCLUSIONS The collagen biomarkers PIIINP and ICTP, in part through pathophysiologically parallel associations with renal function, predicted ChrIRD and total death. Moreover, PIIINP predicted future cancer. These collagen markers may help differentiate healthy from unhealthy aging.

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 &lt; 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 &lt; 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.

Effects of raloxifene and alendronate on bone turnover as assessed by procollagen type I N-Propeptide (PINP)

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S193
Author(s):  
R. Eastell ◽  
A. Rogers ◽  
X. Ni ◽  
J.H. Krege
Keyword(s):  
Bone Turnover ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I

Marked attenuation of production of collagen type I from cardiac fibroblasts by dehydroepiandrosterone

2005 ◽  
Vol 288 (6) ◽  
pp. E1222-E1228 ◽  
Author(s):  
Tomoyuki Iwasaki ◽  
Koji Mukasa ◽  
Masato Yoneda ◽  
Satoshi Ito ◽  
Yoshihiko Yamada ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Protein Accumulation ◽  
Transcriptional Level ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I

Dehydroepiandrosterone (DHEA) is a type of adrenal steroid. The concentrations of DHEA and its sulfate (DHEA-S) in serum reach a peak between the ages of 25 and 30 yr and thereafter decline steadily. It was reported that DHEA-S concentration in humans is inversely related to death from cardiovascular diseases. In this study, we examined the effects of DHEA on regulation of collagen mRNA and collagen synthesis in cultured cardiac fibroblasts. Treatment with DHEA (10−6 M) resulted in a significant decrease in procollagen type I mRNA expression compared with controls. This was accompanied by a significant decrease in procollagen type I protein accumulation in the medium and also a significant decrease in procollagen type I protein synthesis in the cellular matrix. Furthermore, to confirm in vitro results, we administered DHEA to Sprague-Dawley rats, which were treated with angiotensin II for 8 wk to induce cardiac damage. Procollagen type I mRNA expression was significantly decreased and cardiac fibrosis significantly inhibited in DHEA-treated rat hearts without lowering the systolic blood pressure. These results strongly indicate that DHEA can directly attenuate collagen type I synthesis at the transcriptional level in vivo and in vitro in cardiac fibroblasts.

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