scholarly journals Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

2002 ◽  
pp. 187-195 ◽  
Author(s):  
SB Sneppen ◽  
HC Hoeck ◽  
G Kollerup ◽  
OH Sorensen ◽  
P Laurberg ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Bone Mineral ◽  
Type I Collagen ◽  
Treated Group ◽  
Type I ◽  
Mineral Density ◽  
Amino Terminal ◽  
Significant Difference ◽  
Igf I

OBJECTIVE: To evaluate the effect of physiological adult growth hormone (GH) replacement on bones. DESIGN: Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment. METHODS: Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined. RESULTS: IGF-I levels increased from 63.2 microg/l (+/-10.1) to 193.6 (+/- 25.8) microg/l (mean (+/-s.e.)) (P<0.001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P<0.001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of +/- 1.8 (+/- 3.8) in the GH-treated group vs an increase of 1.0 (+/-2.9)) in the placebo-treated group (P=0.002). CONCLUSIONS: No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group.This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.

scholarly journals THE AMINO-TERMINAL PROPEPTIDE OF TYPE I PROCOLLAGEN IN GROWTH HORMONE-DEFICIENT PATIENTS DURING TRANSITION PERIOD

2016 ◽  
Vol 65 (3) ◽  
pp. 271-275
Author(s):  
Mariana Costache-Outas ◽  
◽  
Andra Caragheorgheopol ◽  
Camelia Procopiuc ◽  
Cristina Dumitrescu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Type I Collagen ◽  
Transition Period ◽  
Final Height ◽  
Threshold Value ◽  
Hormone Deficiency ◽  
Type I ◽  
Strong Positive Correlation ◽  
Amino Terminal ◽  
Significant Difference

Introduction. Bone mineral accretion continues beyond the attainment of final height during the transition period. Growth hormone deficiency (GHD) appears to have a significant effect on collagen turnover during childhood and less during adulthood. Amino-terminal pro-peptide of type I collagen (P1NP) is a marker of bone formation with low intra-individual when comparing to IGF1. Material and method. We evaluated 17 male patients diagnosed with GHD during childhood, after retesting GH axis in their transition period after at least 3 months from GH withdrawal. We correlate concentrations of P1NP and IGF1. We determined the predictive value for P1NP in identifying persistent GHD. Results. We found a strong positive correlation between IGF-1 and P1NP in the group of patients who maintained GH deficiency as young adults (r = 0.72, CI [0.02 to 0.94], p = 0.046). A threshold value for the P1NP of - 0.66 SDS predicts persistence of GHD with a sensitivity of 62.5% CI [24.5 to 91.5], specificity 75% CI [47.6 to 92.7] and AUC = 0.719 CI [0.5 0881]. We did not find a significant difference when we compared the AUC for the two parameters (p = 0.29). Conclusion. During the transition period, when the growth velocity is not available anymore, the dynamics of P1NP may be useful in quantifying the effectiveness of GH replacement therapy.

scholarly journals Growth Hormone Replacement Is Important for the Restoration of Parathyroid Hormone Sensitivity and Improvement in Bone Metabolism in Older Adult Growth Hormone-Deficient Patients

2005 ◽  
Vol 90 (6) ◽  
pp. 3371-3380 ◽  
Author(s):  
H. D. White ◽  
A. M. Ahmad ◽  
B. H. Durham ◽  
A. Patwala ◽  
P. Whittingham ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Circadian Rhythm ◽  
Bone Metabolism ◽  
Bone Mineral ◽  
Target Organ ◽  
Type I ◽  
Mineral Density ◽  
Amino Terminal ◽  
Nephrogenous Camp

Alterations in PTH circadian rhythm and PTH target-organ sensitivity exist in adult GH-deficient (AGHD) patients and may underlie the pathogenesis of AGHD-related osteoporosis. GH replacement (GHR) results in increased bone mineral density, but its benefit in AGHD patients over 60 yr old has been debated. To examine the effect of age on changes in PTH circadian rhythm and target-organ sensitivity after GHR, we recruited 22 AGHD patients (12 were &lt;60 yr of age, and 10 were &gt;60 yr of age). Half-hourly blood samples were collected for PTH, calcium, phosphate, nephrogenous cAMP (marker of renal PTH activity), type-I collagenβ C-telopeptide (bone resorption marker), and procollagen type-I amino-terminal propeptide (bone formation marker) before and after 1, 3, 6, and 12 months of treatment with GHR. Significant PTH circadian rhythms were present in both age groups throughout the study. After GHR, PTH decreased and nephrogenous cAMP, adjusted calcium, and bone turnover markers increased in both groups, suggesting increased PTH target-organ sensitivity. In younger patients, the changes were significant after 1 month of GHR, but, in older patients, the changes were delayed until 3 months, with maximal changes at 12 months. Older AGHD patients derive benefit from GHR in terms of improvement in PTH sensitivity and bone metabolism. Their response appears delayed and may explain why previous studies have not shown a positive effect of GHR on bone mineral density in older AGHD patients.

scholarly journals Evaluation of bone mineral density (BMD) and indicators of bone turnover in patients with hemophilia

2018 ◽  
Vol 18 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Mehmet Dagli ◽  
Ali Kutlucan ◽  
Sedat Abusoglu ◽  
Abdulkadir Basturk ◽  
Mehmet Sozen ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Mineral ◽  
Type I ◽  
Healthy Controls ◽  
Mineral Density ◽  
Lymphocyte Ratio ◽  
Significant Difference

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

Overexpression of Mig-6 in Cartilage Induces an Osteoarthritis-Like Phenotype in Mice

2020 ◽  
Author(s):  
Melina Bellini ◽  
Michael Andrew Pest ◽  
Manuela Miranda Rodrigues ◽  
Ling Qin ◽  
Jae-Wook Jeong ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Body Composition ◽  
Articular Cartilage ◽  
Bone Mineral ◽  
Cartilage Degeneration ◽  
Negative Regulator ◽  
Control Group ◽  
Multiple Time ◽  
Mineral Density ◽  
Significant Difference

Abstract Background: Osteoarthritis (OA) is the most common form of arthritis and characterized by degeneration of articular cartilage. Mitogen-inducible gene 6 (Mig-6) has been identified as a negative regulator of the Epidermal Growth Factor Receptor (EGFR). Cartilage-specific Mig-6 knockout (KO) mice display increased EGFR signaling, an anabolic buildup of articular cartilage and formation of chondro-osseous nodules. Since our understanding of the EGFR/Mig-6 network in cartilage remains incomplete, we characterized mice with cartilage-specific overexpression of Mig-6 in this study. Methods: Utilizing knee joints from cartilage-specific Mig-6 overexpressing (Mig-6over/over) mice (at multiple time points), we evaluated the articular cartilage using histology, immunohistochemical staining and semi-quantitative histopathological scoring (OARSI) at multiple ages. MicroCT analysis was employed to examine skeletal morphometry, body composition, and bone mineral density.Results: Our data show that cartilage-specific Mig-6 overexpression did not cause any major developmental abnormalities in articular cartilage, although Mig-6over/over mice have slightly shorter long bones compared to the control group. Moreover, there was no significant difference in bone mineral density and body composition in any of the groups. However, our results indicate that Mig-6over/over male mice show accelerated cartilage degeneration at 12 and 18 months of age. Immunohistochemistry for SOX9 demonstrated that the number of positively stained cells in Mig-6over/over mice was decreased relative to controls. Immunostaining for MMP13 appeared increased in areas of cartilage degeneration in Mig-6over/over mice. Moreover, staining for phospho-EGFR (Tyr-1173) and lubricin (PRG4) was decreased in the articular cartilage of Mig-6over/over mice. Conclusion: Overexpression of Mig-6 in articular cartilage causes no major developmental phenotype; however, these mice develop earlier OA during aging. These data demonstrate that Mig-6/EGFR pathways is critical for joint homeostasis and might present a promising therapeutic target for OA.

EFFECTS OF BISPHOSPHONATES ON OSTEOPOROSIS INDUCED BY DUCHENNE MUSCULAR DYSTROPHY: A PROSPECTIVE STUDY

2020 ◽  
Vol 26 (12) ◽  
pp. 1477-1485
Author(s):  
Wen-bin Zheng ◽  
Yi Dai ◽  
Jing Hu ◽  
Di-chen Zhao ◽  
Ou Wang ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Duchenne Muscular Dystrophy ◽  
Zoledronic Acid ◽  
Muscular Dystrophy ◽  
Bone Mineral ◽  
Type I Collagen ◽  
Type I ◽  
Mineral Density

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD. Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated. Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group ( P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline). Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol. Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid

Treatment with growth hormone and IGF-I in growing rats increases bone mineral content but not bone mineral density

2009 ◽  
Vol 10 (9) ◽  
pp. 1352-1358 ◽  
Author(s):  
Harold N. Rosen ◽  
Vicki Chen ◽  
Antonio Cittadini ◽  
Susan L. Greenspan ◽  
Pamela S. Douglas ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Bone Mineral Content ◽  
Bone Mineral ◽  
Mineral Content ◽  
Mineral Density ◽  
Growing Rats ◽  
Igf I

scholarly journals Treatment of Glucocorticoid-Induced Osteoporosis with Bisphosphonates Alone, Vitamin D Alone or a Combination Treatment in Eastern Asians: A Meta-Analysis

2019 ◽  
Vol 25 (14) ◽  
pp. 1653-1662
Author(s):  
Junjie Wang ◽  
Hongzhuo Li
Keyword(s):  
Vitamin D ◽  
Femoral Neck ◽  
Combination Treatment ◽  
Type I Collagen ◽  
Meta Analysis ◽  
Type I ◽  
Mineral Density ◽  
Bone Specific Alkaline Phosphatase ◽  
Asian Populations ◽  
Significant Difference

Background: Glucocorticoid (GC)-induced osteoporosis and fractures have become a serious problem for Eastern Asians. Bisphosphonates (BPs), vitamin D and a combination treatment are effective methods to prevent and treat GC-induced osteoporosis. Objective: The study aimed to compare the efficacy of BPs, vitamin D and a combination treatment for preventing and managing GC-induced osteoporosis in Eastern Asians. Methods: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane CENTRAL databases was undertaken for randomized controlled trials (RCTs) on the effect of BPs, vitamin D and the combination treatment on GCs-induced osteoporosis in Eastern Asian populations. Primary outcome measures were the change in bone mineral density (BMD) and bone turnover markers. The final search was performed in March 2019. Results: Nine RCTs were included. A total of 545 patients met the inclusion criteria. Compared with vitamin D, BPs and the combination treatment significantly alleviated osteoporosis of the spine and femoral neck in Eastern Asians with GC-induced osteoporosis. At the same time, the change in serum bone-specific alkaline phosphatase (BAP) and serum C-telopeptide of type I collagen (CTX) levels was observed to be significantly less with BPs and the combination treatment with vitamin D alone. No significant difference was found between BPs and the combination treatment in the markers mentioned above. Conclusion: Compared with vitamin D alone, BPs alone and the combination treatment were significantly effective on Eastern Asians with GC-induced osteoporosis. Compared with the combination treatment, BPs alone were observed to be effective enough to increase the BMDs of the spine and femoral neck on both sides and thus prevent GC-induced osteoporosis in Eastern Asians.

scholarly journals The Effects of Growth Hormone Treatment on Bone Mineral Density and Body Composition in Girls with Turner Syndrome

2006 ◽  
Vol 91 (11) ◽  
pp. 4302-4305 ◽  
Author(s):  
Mim Ari ◽  
Vladimir K. Bakalov ◽  
Suvimol Hill ◽  
Carolyn A. Bondy
Keyword(s):  
Bone Mineral Density ◽  
Body Composition ◽  
Turner Syndrome ◽  
Lean Body Mass ◽  
Body Mass ◽  
Bone Mineral ◽  
Bone Age ◽  
Treated Group ◽  
Mineral Density ◽  
Gh Treatment

Abstract Background: Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition. Objective: The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS. Method: In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006. Results: The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1–14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1–L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P &lt; 0.001), whereas body fat percent was lower (P &lt; 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously. Conclusions: Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.

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