Serum Levels of Osteocalcin and Insulin Resistance in Patients with Impaired Glucose Tolerance or New-Onset Diabetes Mellitus After Liver Transplantation.

Liver transplantation (LT) patients are at high risk of developing new-onset diabetes after transplantation (NODAT). Osteocalcin has been proposed as a mediator between bone tissue and glucose metabolism, but its role in the pathogenesis of diabetes is not defined yet. Our objective was to assess the relationship between serum osteocalcin and glucose metabolism parameters in liver transplantation recipients. A total of 187 liver transplantation patients were cross-sectionally studied, 54 of them developed NODAT. None had been diagnosed of diabetes mellitus prior to transplant. In 133 nondiabetic patients, a 75 g oral glucose tolerance test (OGTT) was performed to assess blood glucose, insulin, and C-peptide levels at baseline and 120 min. Serum total osteocalcin was measured at baseline in all patients.After OGTT, 10.5% of LT patients had NODAT criteria, 51.9% showed impaired glucose tolerance, and 37.6% had normal glucose tolerance. Overall, NODAT prevalence was 36.3%. HOMA-IR was significantly higher in NODAT compared with impaired glucose tolerance and normal glucose tolerance groups (p<0.001). Osteocalcin was inversely correlated to HOMA-IR (r=- 0.16, p=0.05), BMI (r=- 0.27, p=0.000) and waist circumference (r=- 0.21, p=0.005). Patients in the lowest osteocalcin tertile (< 16.5 ng/ml) had significantly higher fasting plasma glucose and HOMA-IR index (p=0.029 and 0.037, respectively) than those in medium or highest tertiles. In multiple linear regression analysis, osteocalcin was negatively associated with fasting plasma glucose (standardized ß coefficient-0.16; p=0.041) and 2-h insulin (standardized ß coefficient-0.21; p=0.028). Prevalence of NODAT/impaired glucose tolerance is high in liver transplantation patients and is associated with insulin resistance. In these patients total osteocalcin is inversely associated with plasma glucose level and insulin resistance indexes.

[Translated article] Socioeconomic status, osteoporosis and fragility fractures.

Low socioeconomic status (SES) is associated with a higher risk of fragility fractures, as well as higher mortality in the first-year post-fracture. The SES variables that have the greatest impact are educational level, income level, and cohabitation status. Significant disparities exist among racial and ethnic minorities in access to osteoporosis screening and treatment. In Spain, a higher risk of fractures has been described in people with a low-income level, residence in rural areas during childhood and low educational level. The civil war cohort effect is a significant risk factor for hip fracture. There is significant geographic variability in hip fracture care, although the possible impact of socioeconomic factors has not been analyzed. It would be desirable to act on socioeconomic inequalities to improve the prevention and treatment of osteoporotic fractures.

Socioeconomic status, osteoporosis and fragility fractures. / Estatus socioeconómico, osteoporosis y fracturas por fragilidad.

Low socioeconomic status (SES) is associated with a higher risk of fragility fractures, as well as higher mortality in the first year post-fracture. The SES variables that have the greatest impact are educational level, income level, and cohabitation status. Significant disparities exist among racial and ethnic minorities in access to osteoporosis screening and treatment. In Spain, a higher risk of fractures has been described in people with a low income level, residence in rural areas during childhood and low educational level. The Civil War cohort effect is a significant risk factor for hip fracture. There is significant geographic variability in hip fracture care, although the possible impact of socioeconomic factors has not been analyzed. It would be desirable to act on socioeconomic inequalities to improve the prevention and treatment of osteoporotic fractures.

Results from a national survey on the management of primary hyperparathyroidism.

BACKGROUND: Management of primary hyperparathyroidism (PHPT) continues to be challenging. At the Third International Workshop on PHPT, recent data on this disease were reviewed and new clinical recommendations were developed. There are few data on the influence of new guidelines in clinical practice. AIM: We designed an online survey that was sent to all Spanish hospital endocrinology services. METHODS: The questionnaire included 28 questions about diagnosis and management of PHPT. Ninety-nine of 131 sites (76%), giving health coverage to 70% of Spanish population, completed the survey. RESULTS: The reported incidence of PHPT was 9.95/100,000 person-years. Heighty percent of patients were asymptomatic. Each center performed a median (Q1, Q3) of 12 (6, 20) parathyroidectomies/year. The median (Q1, Q3) percentage of curative interventions (at first trial) was 90% (80, 95). The main reasons for not performing surgery were, by decreasing frequency: surgery contraindication, patient's refusal, loss of monitoring, limited surgery experience. Localization techniques were used in 83% of cases. The main criteria for parathyroidectomy in asymptomatic patients were Ca≥2.875 mmol/l (79%), Tscore ≤-2.5 SD at any site (91%), age <50 yr (80%) and glomerular filtration rate <60 ml/min/1.73 m 2 (82%). Minimally invasive surgery was performed in 42% of centers. Frequency of biochemistry and bone density determinations for non-surgically managed patients was in accordance with international guidelines. CONCLUSIONS: The clinical practice of Spanish endocrinologists is consistent with the recommendations of the guidelines from the Third International Workshop for the management of PHPT.

Postmenopausal women with Colles' fracture have bone mineral density values similar to those of controls when measured with calcaneus quantitative ultrasound.

BACKGROUND: It is a matter of controversy whether or not Colles' fracture is an osteoporotic fracture. Indeed, the usefulness of quantitative ultrasound in distinguishing Colles' fracture from normal fractures is also unclear. METHODS: A cross-sectional case-control study was done on 469 postmenopausal Spanish women, 121 with Colles' fracture and 348 controls. Assessment of risk factors for osteoporosis and measurement of calcaneus quantitative ultrasound were carried out using a Sahara, Hologic device. RESULTS: Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls, and no statistically significant differences were found. We estimated ROC curves for SOS and a score based on a linear combination of height and SOS (SH-Score). The areas under both curves were 0.56 and 0.61, respectively, which was statistically significant. To obtain 5% false-negative and 10% false-positive figures, the T-score cut-off for SOS was -2.45 and -0.045, respectively. Of these, only 9.2% were classified as high risk and 11% as low risk with 79.8% undetermined. CONCLUSIONS: Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls. Nevertheless, ROC curves calculated by a combination of height and SOS showed that quantitative calcaneus ultrasound may be a useful tool for identifying postmenopausal women with Colles' fracture. These results indicate that measuring bone mineral density with ultrasound only captures limited aspects of the pathophysiology of Colles' fractures.

Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment.

Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.

Bone mineral density in male patients with L-thyroxine suppressive therapy and Graves disease.

Little is known about the effects of thyroid hormone excess in male patients. Our aim was to evaluate bone mineral density (BMD), bone turnover markers, and thyroid function in male patients with treated thyroid cancer on long-term suppressive L-T4 therapy (TC) and in male patients with Graves' disease (GD). We studied 49 male patients (aged 45+/-12 years), 17 with TC (29-288 months on L-T4 suppressive therapy; free T4: 1.9+/-0.6 ng/dl [normal< or =2.0]; TSH: 0.2+/-0.3 microU/ml [Normal 0.5-5.0]) and 32 with recent onset GD (<12 weeks, free T4: 2.0+/-1.4 ng/dl; TSH: 1.07+/-1.8 microU/ml; TSHRAb 53+/-45% [normal < 15]). BMD was measured by dual X-ray absorptiometry (DXA, Hologic QDR1000w) at the lumbar spine (L2-L4, LS), femoral neck (FN), and Ward's triangle (WT). Results were expressed as Z-score (SD compared to national controls). Total alkaline phosphatase (ALP), osteocalcin (BGP), iPTH, serum phosphorus, serum, and 24 h urine calcium were measured as bone markers. Age, weight, and body mass index were comparable in both groups. Patients with TC and with GD showed reduced axial BMD (95% confidence interval: LS: TC (-1.27-0.01)(P = 0.046), GD (-1.06 to-0.38)(P < 0.001); FN: TC (-0.82 to-0.16)(P = 0.007), GD (-0.95 to-0.15)(P = 0.008); WT: TC (-0.82 to -0.18)(P = 0.004), GD (-0.97 to -0.08)(P = 0.024). No significant differences in BMD were found between the groups. Among bone markers, total ALP and osteocalcin levels showed higher levels in Graves' disease (ALP: 139+/-76 vs. 88+/-34, P < 0.01; BGP: 7.5+/-3.7 vs. 4.6+/-1.6; P < 0.001). Our data suggest a mild deleterious effect of thyroid hormone excess in the axial bone mass from male subjects. A skeletal status assessed by BMD in male patients with chronic TSH suppression by L-T4 or history of hyperthyroidism is recommended.

[Cushing's syndrome associated with a metastatic medullary carcinoma of the thyroid. A report of 2 cases and a review of the literature]. / Síndrome de Cushing asociado a carcinoma medular de tiroides metastásico. Descripción de dos casos y revisión de la literatura.

An ectopic Cushing syndrome (CS) caused by a medullary thyroid carcinoma (MTC) is an exceptional observation. Two patients are here reported with metastatic MTC, who developed CS two years after the thyroid cancer was diagnosed. A review is also made of clinical and biochemical characteristics of cases with MTC associated with ectopic CS reported in the literature and it is concluded that the cortico-adrenal function in follow-up should be monitored in patients with this type of cancer.

Hormonal and anthropometric predictors of bone mass in healthy elderly men: major effect of sex hormone binding globulin, parathyroid hormone and body weight.

Osteoporosis in men is a significant health problem, and factors associated with bone mass are being investigated. Although osteoporosis is a typical feature of hypogonadism, the influence of testosterone levels and other hormonal factors on bone mass of eugonadal males is unknown. Our aim was to identify several anthropometric and hormonal predictors that could be responsible for the variability in bone mineral density (BMD) in healthy men. One hundred elderly men (age 68 +/- 7 years) were investigated in this cross-sectional study. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral sites (femoral neck, Ward's triangle, trochanter, intertrochanter and total femur). Anthropometric measures were obtained including: weight, height, body mass index (BMI), waist-hip ratio and testicular volume. Hormonal data measures were total, free and bioavailable testosterone, dihidrotestosterone, estradiol, sex hormone binding globulin (SHBG), insulin-like growth factor I (IGF-I), intact parathyroid hormone (iPTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). One subject was excluded because primary hypogonadism was found. SHBG levels were increased in 53.5% of men, and 8% showed a mild increase in iPTH levels. Twenty-eight subjects had densitometric criteria of osteoporosis (T-score < or = -2.5). All BMD sites were positively correlated with body weight (r = 0.29-0.48, p < 0.001) and BMI (r = 0.24-0.47, p < 0.001). A negative correlation between SHBG levels and intertrochanter (IT) and total femur (TL) BMD was found (r = -0.24 and r = -0.22, p < 0.05). After adjusting for age and BMI, SHBG and IGF-I levels were negatively correlated (r = -0.33, p < 0.001). In multiple linear regression analysis independent predictors of bone mass were body weight, SHBG and iPTH levels. The best predictive model accounted for 24-40% of the observed variability of BMD. However, most of the BMD variability was explained by body weight. In conclusion, in our study body weight, SHBG and iPTH levels were predictors of BMD in healthy elderly men.