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.

Effects of everolimus (EVE) on disease progression in bone and bone markers (BMs) in patients (pts) with bone metastases (mets).

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Lowell L. Hart ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Bone Lesion ◽  
Phase Iii ◽  
Type I ◽  
Double Blind ◽  
Mtor Inhibition ◽  
Similar Frequency ◽  
Once Daily ◽  
Amino Terminal

102 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to nonsteroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J et al. NEJM2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effects of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers (BMs) were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a preexisting bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (p < 0.0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively), and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade 1-2 and occurred with similar frequency in EVE (2.9%)- and PBO (3.8%)-treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.

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.

Effects of raloxifene and alendronate on bone turnover as assessed by procollagen type I N-terminal propeptide

2010 ◽  
Vol 22 (6) ◽  
pp. 1927-1934 ◽  
Author(s):  
R. Eastell ◽  
A. Rogers ◽  
X. Ni ◽  
J. H. Krege
Keyword(s):  
Bone Turnover ◽  
Type I ◽  
Procollagen Type ◽  
Procollagen Type I

Effects of everolimus (EVE) on disease progression in bone and bone markers (BM) in patients (pts) with bone metastases (mets).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Michael Gnant ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Bone Lesion ◽  
Phase Iii ◽  
Type I ◽  
Double Blind ◽  
Mtor Inhibition ◽  
Similar Frequency ◽  
Once Daily ◽  
Amino Terminal

512 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to non-steroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J, et al. NEJM. 2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effect of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation, and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a pre-existing bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (P < .0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO, but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively) and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade1/2 and occurred with similar frequency in EVE- (2.9%) and PBO- (3.8%) treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.

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 &gt; 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 &lt; 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 &lt; 0.05), compared with controls. Twenty-four-hour mean PTH increased (P &lt; 0.001) in the acromegalic subjects after treatment, whereas NcAMP and ACa decreased (P &lt; 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.

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

scholarly journals Molecular and Histological Evidence Detailing Clinically Observed Skin Improvement Following Cryolipolysis

2021 ◽  
Author(s):  
W Grant Stevens ◽  
Daniel J Gould ◽  
Linda D Pham ◽  
Joel N Jimenez Lozano
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor Beta ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Body Contouring ◽  
Fold Increase ◽  
Type I ◽  
Gene Markers ◽  
Procollagen Type ◽  
Procollagen Type I

Abstract Background In addition to body contouring, there is anecdotal and supportive clinical evidence of reduced laxity and skin tightening after cryolipolysis. 10,11 Objectives The nature by which cryolipolysis triggers dermal changes has not been established. This study investigated fundamental mechanisms behind clinically observed dermal changes using molecular and immunohistochemistry methods. Methods This feasibility study involved n=7 subjects that received cryolipolysis treatment. Tissue samples were harvested from 3 days to 5 weeks after treatment. RNA-Sequencing examined differential gene expression of major collagens. RNA In Situ Hybridization (RNA-ISH) investigated the distribution of one of the gene markers for collagen Type I (COL1A1). Immunohistochemistry for Procollagen Type I, heat shock protein 47 (HSP47), transforming growth factor beta (TGF-β and Tropoelastin was performed and quantified. Results Gene expression analysis highlighted a gradual upregulation of collagen mRNA genes. RNA-ISH confirmed upregulation of COL1A1 mRNA and showed a homogenous distribution through the dermis. Immunohistochemistry showed increases in protein expression. Quantification revealed 3.62-fold increase of Procollagen Type I (p&lt;0.0071) and 2.91-fold increase of TGF-β (p&lt;0.041); 1.54-fold increase of HSP47 (p&lt;0.007); and 1.57-fold increase of Tropoelastin (p&lt;0.39) compared to untreated areas. Conclusions This study revealed significant induction of molecular and protein markers of Type I collagen, which supports neocollagenesis and may play an essential role in clinically relevant skin improvement. A dermal remodeling process driven by increased TGF-β and higher expression of HSP47 was observed. Overall, these data provide the first evidence of dermal remodeling and clarify the mechanism by which cryolipolysis may induce skin improvement.

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

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