F.J.A. Paula

Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling

Data about the impact of bariatric surgery (BS) and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD), bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16). The data were compared to those obtained for women of normal weight (CG, N = 11) and for obese women (OG, N = 12). Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I) and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 +/- 62 vs OG = 230 +/- 37 vs OGg = 128 +/- 19 ng/mL) were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

Peripheral glucose metabolism in human hyperprolactinaemia

OBJECTIVE Prolactin has important biological actions in several species which include metabolic control and waterlelectrolyte balance. However, human PRL has generally been characterized as a mammotrophic hormone and it is unknown whether PRL has any important metabolic actions. This study was thus conducted to evaluate the effect of hyperprolactinaemia on peripheral muscle glucose metabolism.

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH) secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 +/- 0.2%; range = 3.5-5.0%), 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 +/- 0.4%; range = 6.0-8.5%), and 8 patients with poor metabolic control (group P: HbA1C = 12.5 +/- 1.0%; range: 10.0-18.8%). Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight) and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 +/- 0.01 mmol/l) than in group N (1.21 +/- 0.01 mmol/l) and group G-R (1.22 +/- 0.01 mmol/l). After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01) in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 +/- 2.1 vs G-R = 13.7 +/- 1.6 vs P = 7.5 +/- 0.7 pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

Fisiopatologia da osteoporose induzida por glicocorticóide

Chronic hypercortisolism is the most frequent cause of secondary osteoporosis involving mainly trabecular bone. Approximately 30-35% of the patients with Cushings syndrome present with compression fractures of vertebrae, and the risk of femoral neck fracture is increased in 50% in that population. Several mechanisms have been proposed to explain the association between hypercortisolism and osteoporosis, as the direct action of glucocorticoids in parathyroid glands and bone cells, alterations in the production of prostaglandins, citokines, interleukines, growth hormone (GH), insulin like growth factor I (IGF-I) and gonadal steroids. Contradictory results have been presented in relation to PTH secretion, where normal and high levels have been described. Elevated PTH secretion can occur as a consequence of disturbances in mineral metabolism, i.e. decrease in the intestinal absortion and elevation in the renal excretion of calcium, decrease in the number of parathyroid receptors for 1,25(OH)2D3, abnormalities in the calcium set point for PTH secretion, and alteration in PTH activity. In this review, several pathophysiologic aspects and possible mechanisms involved in the association between osteoporosis and hypercortisolism are discussed.

DXA, bioelectrical impedance, ultrasonography and biometry for the estimation of fat and lean mass in cats during weight loss

BackgroundFew equations have been developed in veterinary medicine compared to human medicine to predict body composition. The present study was done to evaluate the influence of weight loss on biometry (BIO), bioimpedance analysis (BIA) and ultrasonography (US) in cats, proposing equations to estimate fat (FM) and lean (LM) body mass, as compared to dual energy x-ray absorptiometry (DXA) as the referenced method. For this were used 16 gonadectomized obese cats (8 males and 8 females) in a weight loss program. DXA, BIO, BIA and US were performed in the obese state (T0; obese animals), after 10% of weight loss (T1) and after 20% of weight loss (T2). Stepwise regression was used to analyze the relationship between the dependent variables (FM, LM) determined by DXA and the independent variables obtained by BIO, BIA and US. The better models chosen were evaluated by a simple regression analysis and means predicted vs. determined by DXA were compared to verify the accuracy of the equations.ResultsThe independent variables determined by BIO, BIA and US that best correlated (pu2009<u20090.005) with the dependent variables (FM and LM) were BW (body weight), TC (thoracic circumference), PC (pelvic circumference), R (resistance) and SFLT (subcutaneous fat layer thickness). Using Mallows’Cp statistics, p value and r2, 19 equations were selected (12 for FM, 7 for LM); however, only 7 equations accurately predicted FM and one LM of cats.ConclusionsThe equations with two variables are better to use because they are effective and will be an alternative method to estimate body composition in the clinical routine. For estimated lean mass the equations using body weight associated with biometrics measures can be proposed. For estimated fat mass the equations using body weight associated with bioimpedance analysis can be proposed.

Parathyroid hormone secretion in chronic human endogenous hypercortisolism

Osteoporosis is a common manifestation of Cushings syndrome, but the mechanisms responsible for this abnormality have not been defined. With the objective of analyzing parathyroid hormone (PTH) secretion in chronic hypercortisolism (CH), we evaluated 11 healthy subjects and 8 patients with CH, 6 with Cushings disease and 2 with adrenal adenoma. These volunteers were submitted to tests of PTH stimulation through hypocalcemia (EDTA), PTH suppression through hypercalcemia (iv and oral calcium), and evaluation of bone mineral density (BMD) by DEXA. During the test of PTH stimulation, the calcium and magnesium concentrations of the normal and CH groups were similar. Patients with CH showed an increased PTH response to the hypocalcemic stimulus compared to controls. PTH values were significantly higher in the CH group at 70 (17.5 +/- 3.5 vs 10.2 +/- 1.3 pmol/l, P = 0.04), and 120 min (26.1 +/- 5.9 vs 11.3 +/- 1.9 pmol/l, P = 0.008) of EDTA infusion. The area under the curve for PTH during EDTA infusion was also significantly higher in patients with CH than in normal subjects (1867 +/- 453 and 805 +/- 148 pmol l(-1) 2 h(-1), P = 0.02). During the test of PTH suppression, calcium, magnesium and PTH levels of the patients with hypercortisolism and controls were similar. BMD was decreased in patients with hypercortisolism in the spine (0.977 +/- 0.052 vs 1.205 +/- 0.038 g/cm2 in controls, P<0.01). In conclusion, our results show that subjects with CH present decreased bone mass mainly in trabecular bone. The use of dynamic tests permitted the detection of increased PTH secretion in response to a hypocalcemic stimulus in CH patients that may probably be involved in the occurrence of osteoporosis in this state.

Longitudinal evaluation of hepatic osteodystrophy in children and adolescents with chronic cholestatic liver disease

Bone mass loss is a major complication of chronic cholestatic liver disease (CCD). However, the long-term impact of CCD on bone mass acquisition is unknown. We longitudinally assessed bone mineral density (BMD) and factors involved in bone remodeling in 9 children and adolescents with CCD Child-Pugh A (5 boys/4 girls) and in 13 controls (6 boys/7 girls). The groups were evaluated twice, at baseline (T0) and after 3 years (T1), when osteocalcin, deoxypyridinoline, 25-hydroxyvitamin-D, parathyroid hormone, insulin-like growth factor-I (IGF-I), and BMD (L1-L4, proximal femur and total body) were determined. Serum levels of receptor activator for nuclear factor kB ligand (RANKL) and osteoprotegerin were measured only at T1. Lumbar spine BMD was reanalyzed twice: after adjustment for bone age and to compensate for the height factor. Volumetric density was also estimated mathematically in L2-L4. The BMD of L1-L4 was lower in the CCD group (Z-score at T0: control = -1.2 ± 0.8 vs CCD = -2.2 ± 1.4, P < 0.05; T1: control = -0.7 ± 0.8 vs CCD = -2.1 ± 1.1, P < 0.05). Osteocalcin and deoxypyridinoline were similar for the two groups. The CCD group presented lower IGF-I (Z-score at T1: control = 1.4 ± 2.8 vs CCD = -1.5 ± 1.0, P < 0.05) and RANKL (control = 0.465 ± 0.275 vs CCD = 0.195 ± 0.250 pM, P < 0.05) than control. Children with compensated CCD Child-Pugh A showed early impairment of bone acquisition, with the impact being more severe in an initial phase and then tapering in a slowly progressive way. Reduction in endocrine IGF-I has a crucial role in this process.

Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density

The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD) were compared to those of 17 normal individuals (C) and of 9 patients with other forms of hypothyroidism (OH): 4 with hypothyroidism due to inborn errors of thyroid hormone synthesis and 5 with Hashimotos thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+), calcitonin, and intact parathyroid hormone. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C=1.29 +/- 0.08 vs TD=1.34 +/- 0.03 vs OH=1.34 +/- 0.02 mmol/l; P<0.05), and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 5.8 vs TD = 6.6 0.3 vs OH = 43.0 13.4 ng/l). BMD values did not differ significantly between groups (L2-L4: C=1.116 +/- 0.02 vs TD=1.109 +/- 0.03 vs OH=1.050 +/- 0.04 g/cm2). These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

Gene expression profiling of bone marrow mesenchymal stem cells from Osteogenesis Imperfecta patients during osteoblast differentiation

Mesenchymal stem cells (MSCs) are precursors present in adult bone marrow that are able to differentiate into osteoblasts, adipocytes and chondroblasts that have gained great importance as a source for cell therapy. Recently, a number of studies involving the analysis of gene expression of undifferentiated MSCs and of MSCs in the differentiation into multiple lineage processes were observed but there is no information concerning the gene expression of MSCs from Osteogenesis Imperfecta (OI) patients. Osteogenesis Imperfecta is characterized as a genetic disorder in which a generalized osteopenia leads to excessive bone fragility and severe bone deformities. The aim of this study was to analyze gene expression profile during osteogenic differentiation from BMMSCs (Bone Marrow Mesenchymal Stem Cells) obtained from patients with Osteogenesis Imperfecta and from control subjects. Bone marrow samples were collected from three normal subjects and five patients with OI. Mononuclear cells were isolated for obtaining mesenchymal cells that had been expanded until osteogenic differentiation was induced. RNA was harvested at seven time points during the osteogenic differentiation period (D0, D+1, D+2, D+7, D+12, D+17 and D+21). Gene expression analysis was performed by the microarray technique and identified several differentially expressed genes. Some important genes for osteoblast differentiation had lower expression in OI patients, suggesting a smaller commitment of these patients MSCs with the osteogenic lineage. Other genes also had their differential expression confirmed by RT-qPCR. An increase in the expression of genes related to adipocytes was observed, suggesting an increase of adipogenic differentiation at the expense osteogenic differentiation.

Precisão da técnica de absorciometria de raios-x de dupla energia na determinação da composição corporal em gatos

A short-term precision error of the individual subject and the DEXA technique, such as the effect of the repositioning of the cat on the examination table, were established. Four neutered adult cats (BW=4342g) and three females (BW=3459g) were submitted to five repeated scans with and without repositioning between them. Precision was estimated from the mean of the five measurements and expressed by the individual coefficient of variation (CV). The precision error of the technique was estimated by the variance of scan pool (n=35) and expressed in CV for the technique (CVt). The degrees of freedom and confidence intervals were determined to avoid underestimation of precision errors. Bone mineral content (BMC), lean mass (LM), and fat mass (FM) averages were higher (P<0.05) when animals were repositioned. The CVt was significantly higher (P<0.05) for bone mineral density (BMD), LM, and FM when the animals were repositioned. For short-term precision measurements, the repositioning of the animal was important to establish the precision of the technique. The dual energy x-ray absorptiometry method provided precision for body composition measurements in adult cats.