Vitamin D nutritional status and vitamin D regulated antimicrobial peptides in serum and pleural fluid of patients with infectious and noninfectious pleural effusions.

BACKGROUND: Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and ß-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before. METHODS: Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25-(OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and ß-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann-Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis. RESULTS: Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum ß-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH)2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best. CONCLUSIONS: Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of ß-defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions.

Late-onset subcutaneous scalp calcifications in a patient with pseudo-pseudohypoparathyroidism.

Ectopic calcifications and even bone formation have been linked to GNAS gene mutations. A 51-year-old Caucasian female had been diagnosed of pseudo-pseudohypoparathyroidism (PPHP) in 1989. She has always had normal serum parathyroid hormone, calcium, and phosphorus levels. A non-contrast computed tomography of the head was done in 2013 and it showed finely speckled subcutaneous calcifications in the high convexity of the head. Cutaneous exploration did not show any abnormality. We herein report an unusual case of late-onset scalp calcifications in a patient with PPHP.

Transcriptome analysis of mature fruit abscission control in olive.

Mature fruit abscission (MFA) is a genetically controlled process, through poorly characterized mechanisms in fleshy fruit that include extensive transcriptional changes. While global transcriptome analyses have been used to investigate immature fruit abscission in fleshy fruit, no global gene expression changes specific to MFA have been described. Here we use pyrosequencing to characterize the transcriptomes of the olive abscission zone (AZ) during cell separation in order to understand MFA control at the stage of AZ activation. Analysis of gene expression from these AZs reveals that membrane microdomains involving sterols/sphingolipids and remorins together with signaling proteins are potentially involved in MFA. This is accompanied by gene activity related to sphingolipid turnover, suggesting potentially the involvement of long-chain base metabolism in regulating MFA. Activation of vesicle trafficking involving small GTPases is probably required for cell wall modifications during abscission. Analysis of transcription factors indicates that most members of the MYB and bZIP families are abundantly represented in the fruit AZ, and is consistent with a model by which most of the key transcription factors during abscission may regulate downstream processes mostly related to ABA. The data provide the first thorough analysis available for a comprehensive picture of the array of cellular responses controlled by gene expression that lead to MFA in fleshy fruit.

Regulation of polyamine metabolism and biosynthetic gene expression during olive mature-fruit abscission.

Exogenous ethylene and some inhibitors of polyamine biosynthesis can induce mature-fruit abscission in olive, which could be associated with decreased nitric oxide production as a signaling molecule. Whether H2O2 also plays a signaling role in mature-fruit abscission is unknown. The possible involvement of H2O2 and polyamine in ethylene-induced mature-fruit abscission was examined in the abscission zone and adjacent cells of two olive cultivars. Endogenous H2O2 showed an increase in the abscission zone during mature-fruit abscission, suggesting that accumulated H2O2 may participate in abscission signaling. On the other hand, we followed the expression of two genes involved in the polyamine biosynthesis pathway during mature-fruit abscission and in response to ethylene or inhibitors of ethylene and polyamine. OeSAMDC1 and OeSPDS1 were expressed differentially within and between the abscission zones of the two cultivars. OeSAMDC1 showed slightly lower expression in association with mature-fruit abscission. Furthermore, our data show that exogenous ethylene or inhibitors of polyamine encourage the free putrescine pool and decrease the soluble-conjugated spermidine, spermine, homospermidine, and cadaverine in the olive abscission zone, while ethylene inhibition by CoCl2 increases these soluble conjugates, but does not affect free putrescine. Although the impact of these treatments on polyamine metabolism depends on the cultivar, the results confirm that the mature-fruit abscission may be accompanied by an inhibition of S-adenosyl methionine decarboxylase activity, and the promotion of putrescine synthesis in olive abscission zone, suggesting that endogenous putrescine may play a complementary role to ethylene in the normal course of mature-fruit abscission.

"Single nucleotide polymorphisms of the OPG/RANKL system genes in primary hyperparathyroidism and their relationship with bone mineral density".

BACKGROUND: Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κß (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κß) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT. METHODS: We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied. RESULTS: Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA). CONCLUSIONS: Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.

Time course of bone loss in patients with anorexia nervosa.

OBJECTIVE: To evaluate the time course of bone mineral density (BMD) in women with anorexia nervosa (AN) during 2-year follow-up. METHOD: We prospectively studied 51 female with AN aged 18-38 years, and 40 age-matched healthy women (19-34 years). BMD was measured in lumbar spine (LS), femoral neck (FN), and total hip (TH) by DXA. RESULTS: At baseline, weight, body mass index, and lumbar and hip BMD were significantly (p < .001) lower in AN patients than in controls. Patients who gain weight showed a significant increase in BMD at FN (+1.6%; p < .05), and TH (+4.4%; p < .05) and lower nonsignificant changes in LS (+1.3%). Weight at entry, and percent change of weight were significant determinants (p < .05) of the variability in percent change of BMD at FN and TH, whereas weight at entry was the main determinant of bone modifications at lumbar spine. DISCUSSION: Our data emphasize the influence of weight gain in recovery of bone mass in AN patients, especially at the hip.

Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naïve population.

OBJECTIVE: This study examined the main metabolic side effects induced by antipsychotic treatment in a cohort of first episode drug-naïve subjects after the first year of treatment. METHODS: A randomized, open-label, prospective clinical trial was conducted. Participants were 164 consecutive subjects included in a first episode program and never treated with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone. The main outcome measures were changes at 1 year in fasting glucose parameters (glucose, insulin levels and insulin resistance index) and changes in fasting lipid parameters (total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol). RESULTS: 144 of the total sample were evaluated at 1 year. There was a statistically significant increase in the mean values of insulin levels, insulin resistance index, total cholesterol, LDL-cholesterol and triglycerides. No pathological values in fasting glucose plasma levels were found at baseline and there were no changes after 1 year. Weight gain was positively correlated with changes in insulin levels, insulin resistance index and triglyceride levels. We did not detect statistically significant differences between treatments in any of the parameters evaluated. CONCLUSIONS: Fasting glycaemia and insulin concentrations at baseline do not support the hypothesis that schizophrenia is associated with an underlying abnormality in glucose metabolism. The changes in insulin and lipid parameters at 1 year seem to be related to the magnitude of weight gain. There were no significant differences between haloperidol, olanzapine and risperidone concerning metabolic adverse effects after the first year of treatment.

Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women.

BACKGROUND: Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures. METHODS: Four biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA. RESULTS: Age, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p=0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures. CONCLUSION: Some common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.

Mineral metabolism in obese patients following vertical banded gastroplasty.

BACKGROUND: Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation. METHODS: Sixteen morbidly obese patients (14 women, 2 men) with a mean (+/-SD) age of 38 +/- 9 years and a body mass index (BMI) of 47.1 +/- 8.1 kg/m2 were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss. RESULTS: Mean weight loss was 28 +/- 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery. CONCLUSIONS: Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.

Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naïve population.

BACKGROUND: There is little information about weight gain induced by antipsychotics at long-term. OBJECTIVE: To quantify the weight gain induced by first (haloperidol) and second generation antipsychotics (olanzapine and risperidone) in a cohort of drug-naïve subjects after 1 year of treatment. METHODS: This is a prospective, randomized clinical trial, including a representative sample of first episode psychotic incident cases from a population area of 555.000 people. The main outcome measures were changes in body weight and body mass index at 3 months and at 12 months. Both a per protocol analysis and an intention to treat analysis were conducted. RESULTS: A total of 164 drug-naïve patients were included. At 12 months 144 patients were evaluated. Of them, 66% completed the protocol and 34% needed treatment switch. We found statistically significant differences in weight gain at 3 months: 3.8 kg (+/-4.1) for haloperidol, 5.9 kg (+/-5.1) for risperidone and 8.4 kg (+/-5.0) for olanzapine (F=7.045; p=0.002). After 1 year the difference in weight gain had disappeared: 9.7 kg (+/-5.7) for haloperidol, 8.9 kg (+/-8.8) for risperidone and 10.9 kg (+/-7.2) for olanzapine (F=0.817; p=0.445). CONCLUSIONS: Drug-naïve patients experience an extraordinary weight gain after 1 year of treatment with haloperidol, olanzapine or risperidone. The main difference among these treatments is the pattern of weight gain but not the final amount of weight gain.

Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet.

BACKGROUND: The parathyroid-calcium (Ca(2+)-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca(2+) concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca(2+). Increasing the sensitivity of the parathyroid gland to extracellular Ca(2+) by manipulation of the Ca(2+)-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca(2+), accounting for the simultaneous reduction of Ca(2+) and PTH seen in most patients. METHODS: The Ca(2+)-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9-22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca(2+) concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca(2+) concentration to induce hypercalcaemia and maximally inhibit PTH secretion. RESULTS: Significant decreases in ionized Ca(2+) and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca(2+) and to a leftward shift of the Ca(2+)-PTH curve. Significant differences were present in all segments of the Ca(2+)-PTH curves. CONCLUSION: The pathological rightward shift of the Ca(2+)-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.

Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as determinants of bone mineral density.

OBJECTIVES: Bone mineral density (BMD) is a complex trait resulting from the interplay of genetic and acquired factors. The objective of this study was to explore the influence of several anthropometric, lifestyle, genetic, and hormonal factors on BMD and analyze the possible differences in men and women. METHODS: We studied 572 individuals over 50 years of age (381 postmenopausal women and 191 men). Lumbar spine and femoral neck BMD were measured by dual energy x-ray absorptiometry. The free estrogen index (FEI) was calculated as the ratio of serum estradiol to sex hormone binding globulin in 241 individuals. Three polymorphisms in the genes coding for 17-hydroxylase/liase, sulfotransferase, and 5alpha-reductase were studied in DNA isolated from blood cells. RESULTS: Body mass index was strongly correlated to spine and femoral BMD both in women and in men (r = 0.32-0.49; P < 0.001). FEI was also independently correlated with spine BMD in both sexes (r = 0.23 and 0.34, P < 0.01), and with femoral neck in women (r = 0.30). Women with G alleles of the sulfotransferase gene tended to have higher spine BMD than those with C alleles (P = 0.025). No other genotype-related differences in BMD were found. CONCLUSIONS: In conclusion, the results of this study point toward body weight and estradiol levels as major factors determining BMD both in women and in men. A common polymorphism of the sulfotransferase gene also appears to be associated to spine BMD in women.

[Electrolyte disorders following colonic cleansing for imaging studies]. / Alteraciones electrolíticas inducidas por la preparación para los estudios de imagen del colon.

BACKGROUND AND OBJECTIVE: An adequate bowel cleansing is needed prior to radiologic and endoscopic procedures. However, it may have a number of adverse effects, including abnormalities of calcium-phosphorus homeostasis. PATIENTS AND METHOD: This was an observational prospective study in a hospital practice setting. We included consecutive inpatients (n = 47) subjected to a barium enema or colon endoscopy. Prior cleansing was done as indicated by the attending physician by using a low-salt oral poliethylenglicol (PEG) solution, oral sodium phosphate or a phosphate-containing enema. RESULTS: PEG solution frequently caused mild increases in serum sodium, and decreases in serum potassium. Oral phosphate caused a significant increase in serum phosphorus and parathormone concentrations, whereas it decreased serum calcium. Mild hyperphosphatemia was found in 57% of cases, and hypocalcemia in 36%. Phosphate enema also increased serum phosphate, causing mild hyperphosphatemia (33% cases). Although in the whole subgroup of enema-treated patients there were no significant changes in serum calcium, mild hypocalcemia was found in 27% cases. CONCLUSIONS: Bowel cleansing procedures, particularly those using oral phosphate salts, frequently induce hyperphosphatemia and other abnormalities in serum electrolytes. Although usually transitory and without overt clinical consequences, clinicians should be aware of this potential risk, especially in elderly patients and those with impaired renal function.

Aromatase gene and osteoporosis: relationship of ten polymorphic loci with bone mineral density.

Aromatase activity appears to be important for bone homeostasis in postmenopausal women. In fact, therapy with aromatase inhibitors is associated with bone loss and fractures. A common biallelic A/G polymorphism in the 3'-untranslated region (UTR) of CYP19-aromatase gene has been associated with differences in gene transcription and the risk of estrogen-responsive tumors. We explored the relationship of such a polymorphism and other 9 polymorphisms situated within or near CYP19 gene with bone mass. The study group comprised 286 postmenopausal women. DNA was isolated from peripheral blood. Biallelic and insertion/deletion polymorphisms were analyzed with exonuclease assays using TaqMan probes. A microsatellite polymorphism in intron 4 was studied by capillary electrophoresis. Bone mineral density (BMD) was determined by DXA. In this cross-sectional study, the postmenopausal decrease in bone mass appeared to be slower in women with AA genotype in the 3'UTR, than in those with AG or GG genotypes. Consequently, there were significant genotype-related differences in BMD. In women after age of 60, hip T-scores were: AA -1.3 +/- 0.1, AG -1.3 +/- 0.2, GG -1.9 +/- 0.1 (P = 0.002). Lumbar spine T-scores were: AA -1.9 +/- 10.2, AG -2.2 +/- 0.1, GG -3.0 +/- 0.2 (P = 0.001). Moreover, GG genotype showed a trend for lower free estrogen levels. This polymorphism was strongly linked to a tetranucleotide repeat in intron 4, as well as to other biallelic polymorphisms situated between 3'UTR and I.2 promoter regions. They all were associated with BMD. However, biallelic polymorphisms in the extreme 5' region of CYP19 and two polymorphisms in neighbor genes were not associated with BMD. In conclusion, common variations of CYP19-aromatase are associated with differences in BMD that seem to be important from an individual as well as from a population perspective.

Effect of transdermal nitroglycerin on inflammatory mediators in patients with peripheral atherosclerotic vascular disease.

OBJECTIVE: To demonstrate that nitroglycerin improves biological markers of arterial inflammation in patients with peripheral vascular disease. BACKGROUND: Atherosclerosis is an inflammatory disease in which there is an increase in active inflammation markers such as C-reactive protein and other factors released by endothelial cells. Nitroglycerin acts by a chemical liberation of nitric oxide. We have previously published the results from several controlled clinical trials confirming an anti-inflammatory action of nitroglycerin. METHODS: Forty patients with peripheral vascular disease entered a randomized, double-blind, placebo-controlled pilot study for 6 weeks. Twenty-one patients were treated with continuous application of a transdermal nitroglycerin patch (15 mg/24 hours) on the anterior face of the thigh. Venous blood samples were obtained before treatment and 2 and 6 weeks after. We measured plasma levels of C-reactive protein, cGMP (also intraplatelet cGMP), E-selectin, ICAM, VCAM-1, IL-6, and nitrites/nitrates. RESULTS: No biological parameter was modified in the placebo group. On the contrary, nitroglycerin significantly reduced plasma levels of C-reactive protein and sE-selectin and increased the levels of intraplatelet cGMP. CONCLUSIONS: The results of this preliminary study show that nitroglycerin has an anti-inflammatory action in patients with peripheral vascular disease. This may provide a new therapeutic approach to understanding the efficacy of nitrovasodilators in the improvement of atherosclerotic syndromes.

Hypothalamic-pituitary-adrenocortical axis function in patients with polymyalgia rheumatica and giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are 2 closely related syndromes affecting elderly people. One of the most striking features of these conditions is the development of the disease in an almost exclusive manner in people older than 50 years. Despite this close association with age, the pathogenic mechanisms that could explain this age-related predisposition are unknown. Aging is accompanied by a number of quantitative and qualitative changes in the endocrine system that may predispose to several pathologic conditions that occur in the elderly. OBJECTIVE: To explore the hypothalamic-pituitary-adrenal axis in PMR and GCA. METHODS: Basal levels of adrenal hormones as well as the response to low-dose adrenocorticotropin hormone (ACTH) were investigated in 20 patients with active untreated disease and compared with levels in 16 healthy age-matched controls. RESULTS: Male patients with active disease had low basal levels of androstenedione compared to the controls. After low-dose ACTH challenge, cortisol and dehydroepiandrosterone reached higher levels in patients than in healthy subjects, indicating that the adrenal gland function was not suppressed. Furthermore, the authors did not find a clear relationship between the levels of acute phase reactants and adrenal hormones in the patient population. CONCLUSIONS: The authors' findings are probably more compatible with the hypothesis that the abnormalities found in the patient group are the consequences of chronic illness rather than a crucial factor contributing to the pathogenesis of the disease.

A common polymorphism in the 5'-untranslated region of the aromatase gene influences bone mass and fracture risk.

OBJECTIVE: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5'-untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD). DESIGN: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women. METHODS: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry. RESULTS: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P=0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles. CONCLUSIONS: A common biallelic polymorphism in the 5'-untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.

Bone disease in long-term adult kidney transplant patients with normal renal function.

BACKGROUND: In successful renal transplantation, the degree of renal function recovery is usually incomplete and information is scarce about the abnormalities of mineral metabolism in long-term adult renal recipients with normal renal function. This study was designed to investigate bone mineral metabolism in patients with a long-term normal functioning kidney. METHODS: Twenty-nine adult asymptomatic renal transplant (RT) recipients with stable graft function for more than 10 years and serum creatinine <2 mg/dL were studied. They were classified into two groups according to glomerular filtration rate: Group A (N = 12; nine men, three women)>70 mL/min (x: 126 +/- 55 mL/min) and Group B (N = 17; nine men, eight women) <70 mL/min (x: 56 +/- 11 mL/min). Circulating biochemical markers of bone remodelling, bone histomorphometry, and densitometry (lumbar spine and hip) were obtained to investigate bone disease in these patients. RESULTS: Serum PTH was slightly elevated in 10 patients (83%) in group A. Serum PTH levels were positively related to serum calcium, osteocalcin, BAP, telopeptide, OH-proline, and creatinine. There was no histologic data to support overactivity on bone in this group of patients, with only one showing high bone turnover. Mineralization was prolonged in 34% of patients. Twenty-two patients (75%) exhibited normal bone turnover. In the group with GFR>70 mL/min the prevalence of mineralization defect in the presence of normal serum levels of calcitriol suggested vitamin D resistance. Lumbar and femoral neck osteoporosis was present in 25% and 33% of patients in group A, and 23% and 53% in group B, respectively. T-score at lumbar spine was negatively correlated with months since transplantation. Patients under treatment with cyclosporine (CsA) showed increased concentrations of osteocalcin and D-pyr and higher lumbar bone mineral density (BMD), but bone histomorphometry was not influenced by CsA. CONCLUSION: Patients with long-term renal transplantation with normal renal function frequently present with slight increases in PTH, but without an effect on bone histology. CsA did not induce changes in bone histology and delayed mineralization was frequently observed.