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Comparative Study 2007; 28(5): 621-628 PubMed PMID: 17984937 Citation  Keywords:  Acromegaly:blood, Adult, Aged, Aged, 80 and over, Bone Density:physiology, Bone Resorption:blood, Estradiol:blood, Female, Follicle Stimulating Hormone:blood, Human Growth Hormone:blood, Humans, Hypogonadism:blood, Insulin-Like Growth Factor I:analysis, L.   

OBJECTIVES: The aim of our study was to evaluate bone metabolism and bone mineral density (BMD), and to indicate the main determinants of these parameters in a large group of patients with active acromegaly.

METHODS: A group of 121 active acromegalics, aged 23-80 years, from a single endocrinological center was studied. Serum GH, IGF-I, LH, FSH, PRL, estradiol/testosterone, osteocalcin (OC), type I collagen carboxyterminal telopeptide (ICTP) as well as BMD by DXA at spine L2-L4, femoral neck, Ward's triangle and trochanter were measured.

RESULTS: Serum OC and ICTP concentrations were elevated (mean+/-SEM: 31.7+/-2.2 microg/L, p<0.001; 7.3+/-0.5 microg/L, p<0.001, respectively), and positively correlated with each other, as well as with IGF-I. BMD (Z-scores) was increased at L2-L4, femoral neck and trochanter (0.35+/-0.15, p=0.016; 0.60+/-0.11, p<0.001 and 0.59+/-0.13, p<0.001; respectively). The main determinants of Z-scores and ICTP were gonadal status and gender, while of OC was IGF-I. Eugonadal acromegalics had higher than normal serum OC and ICTP, as well as Z-scores at all measured sites. Hypogonadal patients (2/3 of the population) had significantly higher serum ICTP concentrations and lower BMD at all sites, when compared to eugonadal acromegalics. Thirty five percent of hypogonadal subjects had T-score<-1. Men had significantly higher serum ICTP and lower Z-scores than women.

CONCLUSIONS: (i) In active acromegaly, enhanced IGF-I-dependent bone turnover and increased BMD is observed. (ii) In hypogonadal acromegalics, high bone resorption decreases BMD and may lead to osteoporosis. (iii) There is a smaller increase in bone resorption and greater increase in BMD in women with acromegaly than in men....

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Comparative Study 2007; 28(4): 484-488 PubMed PMID: 17693962 Citation  Keywords:  Aging:physiology, Albinism:genetics, Animals, Antithyroid Agents:adverse effects, Bone Density:drug effects, Bone Development:drug effects, Carbimazole:adverse effects, Hormone Replacement Therapy:methods, Hypothyroidism:chemically induced, Rats, Rats, Mu.   

: To evaluate the effect of carbimazole induced hypothyroidism and thyroxine replacement, on the growth of long bones of albino rats of different age groups. Experimental albino rats were developed with carbimazole and carbimazole plus thyroxine for a period of six weeks. At the end of the experiment the animals were sacrificed, fixed and processed to demonstrate the bony and cartilaginous parts. The ulna and tibia of both sides were measured for intact bone length & diameter and the data compared. The reduction in length and circumference observed, at the end of experiment, in ulna was 10.89%, & 11.94% and in tibia it was 12.52%, 14.81% in carbimazole treated group respectively, while in carbimazole plus thyroxin treated group the reduction in length & circumference of ulna was 1.37% & 1.88% and in tibia it was 1.86% & 3.08% respectively. They were compared to their age matched controls. The reduction in length and circumference in ulna was 5.58% & 6.25% and 6.42% and 5.88% in tibia respectively among the carbimazole treated animals while in the carbimazole plus thyroxine treated animals the reduction was only 0.63% and 3.12% in ulna and 0.91% and 1.06% in tibia respectively. The results show that hypothyroidism and its replacement therapy affects the endochondral as well as periosteal bone growth and results in reduction in length as well as circumference of long bones....

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Controlled Clinical Trial 2006; 27(4): 513-515 PubMed PMID: 16891991 Citation  Keywords:  Aged, Analgesics:administration & dosage, Bone Density Conservation Agents:administration & dosage, Diphosphonates:administration & dosage, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Osteitis Deformans:complications, Pain:drug therapy, Pai.   

INTRODUCTION: Although an analgesic effect is an essential component of the mode of action of bisphosphonates, its physiological mechanisms are still unclear. Beta-endorphin release plays an important role in the analgesic effect of both calcitonin and raloxifene. As patients with Paget's disease receive large doses of bisphosphonates within relatively short time periods, we examined whether repeated pamidronate infusion therapy would cause measurable change in beta-endorphin levels

MATERIALS & METHODS: Visual analog scale (VAS) scores of pain intensity, beta-endorphin levels, and alkaline phosphatase activity of 11 patients with Paget's disease (7 with the mono- and 4 with the polyostotic form) were determined at baseline, as well as after 3 and 6 infusions (on Days 6 and 12 of treatment, respectively). Eleven untreated patients with Paget's disease (7 with the mono- and 4 with the polyostotic form) served as controls.

RESULTS: It was established that in the course of pamidronate infusion therapy BE levels remained constant, whereas the values in serum alkaline phosphatase and pain intensity scores were significantly reduced.

CONCLUSIONS: Although high-dose pamidronate therapy does mitigate pain substantially (as demonstrated by the reduction of VAS scores), its analgesic action is probably unrelated to the enhancement of beta-endorphin release....

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Journal Article 2006; 27(1-2): 183-188 PubMed PMID: 16648806 Citation  Keywords:  Absorptiometry, Photon, Acromegaly:blood, Adult, Aged, Body Mass Index, Bone Density:physiology, Cytokines:blood, Enzyme-Linked Immunosorbent Assay, Female, Human Growth Hormone:blood, Humans, Male, Middle Aged, Sex Characteristics, Testosterone:blood,.   

OBJECTIVES: Elevated cytokines levels were observed as a marker of increased bone resorption in certain diseases. The aim was to assess serum levels of selected cytokines in acromegaly, regarding to different disease's stages, gonadal function, gender and character of BMD change.

METHODS: The study was carried out in 62 patients with acromegaly (40 women, 22 men) aged 26-75 years in various stages of the disease. The controls were 30 healthy, age- and sex-matched subjects. Serum cytokines concentration was assessed using ELISA method.

RESULTS: We have shown higher (p=0.044) concentrations of TGF-beta in male patients with active acromegaly than in cured males. When the influence of all cytokines studied on BMD using multiple regression analysis was carried out, the borderline (p=0.099) statistical significance was achieved (regression coefficient B=0.68271) according to TGF-beta and trochanter major BMD. IL-6 and TNF-alpha were higher (p=0.062, and p=0.098, respectively) in these acromegalic patients, in which gain of trochanter major BMD occurred. IL-1beta levels were lower in patients with ultradistal radius and 1/3 distal radius BMD gain (p=0.007, and p=0.009, respectively). Lower TGF-beta levels (p=0.077) were shown in patients with 1/3 distal radius gain. IL-6 levels were higher in patients with total body BMD gain (p=0.059).

CONCLUSIONS: The relations between TGF-beta and acromegaly activity in men, and trochanter major BMD in both sexes were documented. Concentrations of all cytokines studied correlated with the BMD changes in different bone sites. Noteworthy is homogeneity of the secretory character of cytokines studied according to BMD changes within particular skeleton sites....

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Journal Article 2006; 27(1-2): 225-230 PubMed PMID: 16648797 Citation  Keywords:  Absorptiometry, Photon, Adolescent, Adult, Aged, Aldehydes:blood, Body Composition:physiology, Body Mass Index, Bone Density:physiology, Female, Glucose Intolerance:physiopathology, Glucose Tolerance Test, Human Growth Hormone:blood, Humans, Lipid Peroxid.   

OBJECTIVES: Growth hormone (GH) deficiency in adults is associated with a higher risk of atherosclerosis and cardiovascular disease. It has recently been suggested that enhanced oxidative stress may be implicated in vascular (and probably other) disturbances, occurring in GH-deficient subjects. The aim of the study was to evaluate serum levels of lipid peroxidation (LPO) products in adult patients with severe GH deficiency during insulin tolerance test (ITT), and to estimate the relationships between LPO and GH, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and other parameters of metabolic processes.

MATERIAL AND METHODS: Twelve adult patients with severe GH deficiency hospitalized in our department and 12 healthy volunteers, matched for sex, age and body mass index (BMI), were enrolled in the study. Peripheral blood was collected during ITT. The concentrations of malondialdehyde + 4-hydroxyalkenals (MDA+4-HDA), as an index of LPO, were measured in blood serum.

RESULTS: Serum LPO level was approximately twice as high in GH-deficient patients as in the controls at each time point of ITT. A positive correlation was found between bone mineral density in the lumbar spine and GH concentration in GH-deficient patients. A positive correlation was found between LPO and BMI in the controls, but no such correlation was observed in GH-deficient patients.

CONCLUSION: The increased LPO in GH-deficient patients may indicate enhanced oxidative stress within the vascular compartment and, possibly, in other tissues, which may contribute to the proatherogenic state and corresponding organ disturbances in GH-deficient patients, independently from conventional risk factors....

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Journal Article 2003; 24(5): 314-320 PubMed PMID: 14647003 Citation  Keywords:  Animals, Bone Density, Female, Mandible:diagnostic imaging, Rats, Rats, Wistar, Superior Cervical Ganglion:surgery, Sympathectomy, Tomography, X-Ray Computed, Tooth Eruption:physiology,.   

OBJECTIVE: To assess the effect of local sympathectomy on mandibular bone during tooth eruption in rats.

METHODS: The effect of a unilateral superior cervical ganglionectomy (Gx) on morphometry of ipsi- and contralateral mandible and volumetric bone density (as assessed by peripheral computed tomography) was examined 30 days after surgery.

RESULTS: Only a few mandibular morphometric parameters decreased significantly after denervation in rats subjected to a unilateral Gx and a contralateral sham-operation. Mandibular volumetric bone density decreased significantly after sympathetic denervation. In a second experiment, carried out under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral Gx, a significant interaction "denervation x type of eruption" was found for most morphometric parameters. Further analysis indicated higher morphometric indexes in denervated mandibles than in the innervated ones under impeded incisor eruption conditions, and lower morphometric indexes in denervated mandibles than in the innervated ones under unimpeded incisor eruption conditions. Unimpeded eruption augmented total volumetric bone density providing the innervation was intact and caused opposite effects on cortical volumetric bone density in the presence of innervation (increase) or absence of innervation (decrease). Trabecular volumetric bone density decreased significantly after sympathetic denervation.

CONCLUSION: The results support a role of the sympathetic nervous system in the regulation of bone remodeling....

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