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 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.

scholarly journals Serum 25(OH)D3 vitamin status of elderly Finnish women is suboptimal even after summer sunshine but is not associated with bone density or turnover

2010 ◽  
Vol 162 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Tuula Pekkarinen ◽  
Ursula Turpeinen ◽  
Esa Hämäläinen ◽  
Eliisa Löyttyniemi ◽  
Henrik Alfthan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Density ◽  
Bone Turnover ◽  
Population Based ◽  
Type I ◽  
Vitamin D Status ◽  
Mineral Density ◽  
Type I Procollagen ◽  
Before And After ◽  
Before And After Summer

ObjectiveConcentrations of 50 and 75 nmol/l are proposed as serum 25-hydroxyvitamin D (25(OH)D) target for older people from the view of bone health. We evaluated vitamin D status of elderly Finnish women in light of these definitions, its relationship to bone mineral density (BMD) and turnover, and improvement by summer sunshine.DesignPopulation-based study.MethodsA total of 1604 ambulatory women aged 62–79 years were studied; 66% used vitamin D supplements. Serum 25(OH)D3was measured with HPLC before and after summer, and heel BMD in spring. In subgroups, serum parathyroid hormone (PTH) and type I procollagen aminoterminal propeptide (PINP) were analyzed.ResultsIn spring, 60.3% of the women had 25(OH)D3≤50 nmol/l, and the target of 75 nmol/l was reached by 9.1%. For supplement users, the respective numbers were 52.1 and 11.9%. Serum 25(OH)D3did not determine BMD or bone turnover measured by serum PINP. Summer sunshine increased serum 25(OH)D3by 17.4% (P<0.0001), but in autumn 84% of the subjects remained under the target of 75 nmol/l. In supplement users, PTH remained stable but decreased in others during summer (P=0.025).ConclusionsVitamin D status of elderly Finnish women is suboptimal if 25(OH)D3levels of 50 or 75 nmol/l are used as a threshold. It is moderately increased by supplement intake and summer sunshine. However, 25(OH)D3concentrations did not influence bone density in terms of serum PINP and bone turnover rate.

scholarly journals Serum Sclerostin Levels Are Decreased in Adult Patients With Different Types of Osteogenesis Imperfecta

2014 ◽  
Vol 99 (2) ◽  
pp. E311-E319 ◽  
Author(s):  
Roland Kocijan ◽  
Christian Muschitz ◽  
Astrid Fahrleitner-Pammer ◽  
Karin Amrein ◽  
Peter Pietschmann ◽  
...  
Keyword(s):  
Body Composition ◽  
Mineral Content ◽  
Adult Patients ◽  
Type I ◽  
Healthy Controls ◽  
Amino Terminal ◽  
Type I Procollagen ◽  
Different Types ◽  
Turnover Markers

Context: There are no specific biochemical bone markers available for osteogenesis imperfecta (OI), and the role of sclerostin as a key regulator of bone formation in OI is unknown. Objectives: We aimed to evaluate the role of sclerostin and its association with bone turnover markers as well as body composition parameters in adult patients with different types of OI. Design, Setting, and Participants: This was a case-control study in 27 adult patients and 50 healthy age- and gender-matched controls. Main Outcome Measures: Serum sclerostin levels and bone turnover markers including serum osteocalcin, amino terminal propeptide of type I procollagen, and CrossLaps as well as body composition parameters were determined in mild OI stage I (OI-I) and moderate-severe OI stages III-IV (OI-III-IV), according to Sillence classification. Data were compared with healthy controls. Results: Sclerostin levels were significantly lower in OI-I (19.9 ± 10.9 pmol/L; P &lt; .001) and OI-III-IV (13.3 ± 10.0 pmol/L; P &lt; .001) compared with healthy adults (45.3 ± 14.9 pmol/L), even after adjustment for age, sex, bone mineral content, and body mass index. CrossLaps and PTH were significantly lower in OI-I (0.197 ± 0.15 ng/L; P = .007 and 33.7 ± 19.1 pg/L; P = .033, respectively) and OI-III-IV (0.221 ± 0.18 ng/L; P = .039, and 27.9 ± 14.7 pg/L; P = .001, respectively) than in healthy controls (0.322 ± 0.15 ng/L and 45.0 ± 16.6 pg/L). Amino-terminal propeptide of type I procollagen was below the reference range for OI-I and OI-III-IV. Patients with OI were shorter and lighter and had a decreased bone mineral content (P &lt; .001) but similar fat distribution and lean body mass, compared with controls. Serum sclerostin levels were not related to any bone marker except osteocalcin, the number of prevalent fractures, or body composition readings. Conclusion: Decreased sclerostin levels in OI might reflect a down-regulation or negative feedback mechanism to prevent further bone loss.

Physical properties of the amino-terminal precursor-specific portion of type I procollagen

Biochemistry ◽  
1977 ◽  
Vol 16 (18) ◽  
pp. 4026-4033 ◽  
Author(s):  
Jurgen Engel ◽  
Peter Bruckner ◽  
Udo Becker ◽  
Rupert Timpl ◽  
Bea Rutschmann
Keyword(s):  
Physical Properties ◽  
Type I ◽  
Amino Terminal ◽  
Type I Procollagen

scholarly journals Diagnostic value of amino-terminal peptide of type I procollagen when retesting GH deficiency in the transition period

2015 ◽  
Author(s):  
Mariana Costache-Outas ◽  
Camelia Procopiuc ◽  
Andra Caragheorgheopol ◽  
Raluca Costache ◽  
Simona Fica
Keyword(s):  
Transition Period ◽  
Gh Deficiency ◽  
Diagnostic Value ◽  
Type I ◽  
Amino Terminal ◽  
Type I Procollagen

scholarly journals Temporal Change in Biomarkers of Bone Turnover Following Late Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix in Postmenopausal Women with Osteopenia

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Manjula Hettiarachchi ◽  
Rachel Cooke ◽  
Catherine Norton ◽  
Phil Jakeman
Keyword(s):  
Vitamin D ◽  
Postmenopausal Women ◽  
Bone Remodeling ◽  
Type I Collagen ◽  
Dietary Intervention ◽  
Type I ◽  
Protein Matrix ◽  
Procollagen Type ◽  
Amino Terminal ◽  
Fortified Milk

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0–4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a −32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was −10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.

scholarly journals Markers of Bone Turnover and 25-Hydroxy Vitamin D in Women with Type 2 Diabetes and Newly Diagnosed Osteoporosis

2016 ◽  
Vol 23 (1) ◽  
Author(s):  
Raluca Nan ◽  
Adrian Cursaru ◽  
Daniel Grigorie ◽  
Alina Şucaliuc ◽  
Ramona M. Drăguţ ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin D ◽  
Bone Turnover ◽  
Newly Diagnosed ◽  
Markers Of Bone Turnover ◽  
25 Hydroxy Vitamin D

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

1997 ◽  
Vol 136 (3) ◽  
pp. 282-289 ◽  
Author(s):  
Gerd Finkenstedt ◽  
Rudolf W Gasser ◽  
Günter Höfle ◽  
Christine Watfah ◽  
Leo Fridrich
Keyword(s):  
Lumbar Spine ◽  
Bone Mass ◽  
Bone Turnover ◽  
Gh Deficiency ◽  
Controlled Study ◽  
Type I ◽  
Adult Onset ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
Igf I

Abstract It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a doubleblind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2·4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2·39±0·02 vs 2·32±0·02 mmol/l, P=0·037) and phosphate (0·97±0·06 vs 0·75±0·05 mmol/l, P=0·011) increased and the index of phosphate excretion (0·03±0·03 vs 0·19±0·02, P<0·001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64·8±11·8 vs 17·4±1·8 ng/ml, P<0·001; procollagen type I carboxyterminal propeptide (PICP), 195·3±26·4 vs 124·0±15·5 ng/ml, P=0·026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8·9±1·2 vs 3·3±0·5 ng/ml, P<0·001; urinary hydroxyproline, 0·035±0·006 vs 0·018±0·002 mg/100 ml glomerular filtration rate, P=0·009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306·5±45·3 vs 88·7±22·5 ng/ml, P<0·001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1·194±0·058 vs 1·133±0·046 g/cm2, P=0·015), femoral neck (1·009±0·051 vs 0·936±0·034 g/cm2, P=0·004), Ward's triangle (0·801±0·055 vs 0·816±0·04 g/cm2, P=0·019) and the trochanteric region (0·869±0·046 vs 0·801±0·033 g/cm2, P=0·005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < −1·0 s.d.) increased more than in those with normal bone mass (lumbar spine 11·5 vs 2·1%, P=0·030, and femoral neck 9·7 vs 4·2%, P=0·055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk. European Journal of Endocrinology 136 282–289

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