Guillermo Martínez

Comparative effects of teriparatide and risedronate in glucocorticoid-induced osteoporosis in men: 18-month results of the EuroGIOPs trial.

Data on treatment of glucocorticoid‐induced osteoporosis (GIO) in men are scarce. We performed a randomized, open‐label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T‐score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1–L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high‐resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X‐ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18‐month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE‐derived strength than risedronate.

Bone Mineral Density in Children and Adolescents with Diabetes Mellitus Type 1 of Recent Onset

Abstract. There is still controversy over the impact of diabetes control and duration on bone mass and growth parameters in children and adolescents with insulin-dependent diabetes mellitus (IDDM). The aim of this study was to assess bone mineral density (BMD) at axial and appendicular sites, in children with noncomplicated IDDM of recent onset, and its relation to metabolic control and auxological parameters (weight, height, and puberal stage). Fifty-five young Spanish IDDM, otherwise healthy patients (26 males, aged (SD 9.7 ± 4.3 years) and 29 females, aged (SD 11.2 ± 3.8 years) were studied. Duration of diabetes was 1–13.8 years. Two hundred eighty-two age-matched, healthy, Spanish children served as controls. HbA1 was assayed by high pressure liquid chromatography (HPLC) and BMD was measured using dual X-ray absorptiometry (DXA) densitometry at the spine and forearm. Results showed a Gaussian BMD distribution of patients according to sex and age, without sexual-stage differences. There was no correlation between BMD and glycated hemoglobin (average life disease or last HbA1 values) or duration of the disease; moreover, no differences in bone mass were found between <3 and ≥3 years of disease duration. Diabetes impact index (mean HbA1× duration of disease in months) showed no significant influence of diabetes control on BMD. We could not demonstrate any impact of diabetes on BMD and growth parameters in children with IDDM of short duration.

Long-term follow-up of bone mineral density in Addison's disease

background and aims There is conflicting evidence regarding the long‐term effects of long‐term glucocorticoid replacement therapy (GRT) on bone mineral density (BMD) in patients with chronic adrenal insufficiency. Our aim was to evaluate bone turnover and changes in BMD in patients on GRT.

Effect of Weight Loss on High-Molecular Weight Adiponectin in Obese Children

Our aim was to determine the influence of weight reduction on total (T‐) and high‐molecular weight (HMW‐) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual‐energy X‐ray absorptiometry (DXA) and serum levels of T‐ and HMW‐adiponectin, resistin, leptin, leptin soluble receptor (sOB‐R), tumoral necrosis factor‐α and interleukin‐6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T‐adiponectin was higher (P < 0.01; confidence interval (+0.04) — (+0.15)) and HMW‐adiponectin lower (P < 0.001; confidence interval (−0.45) − (−0.21)) in OB children than in controls. A reduction in body fat increased T‐ and HMW‐adiponectin and sOB‐R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin‐6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor‐α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T‐adiponectin (P < 0.05). HMW‐adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T‐adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T‐ nor HMW‐adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T‐ and HMW‐adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.

Regional fat distribution in adolescents with anorexia nervosa: effect of duration of malnutrition and weight recovery

OBJECTIVE This study addresses the influence of the duration of malnutrition and the effect of weight recovery on regional fat mass distribution in moderately malnourished adolescents with anorexia nervosa (AN). STUDY DESIGN We measured total and regional fat mass and leptin levels in 42 restrictive AN female adolescents and 23 controls. AN patients, followed over 2 years, were divided into three groups: prolonged moderate malnutrition (PM; secondary amenorrhea for over 1 year, n = 14); SM, short period of moderate malnutrition (secondary amenorrhea for less than 1 year, n = 13); and R, recovered from AN (BMI, body mass index and menses recovered for over 6 months, n = 15). RESULTS Total, trunk, and extremity fat mass were reduced in the PM and SM groups (P < 0.05), whereas only PM patients showed altered regional fat distribution with a low trunk to extremity fat ratio (P < 0.05). BMI increased after 12 months only in the SM group (P < 0.05), with menses resumption in 69% of these patients and BMI normalization at 24 months. Their regional fat distribution was similar to controls throughout the study. No difference in any parameter was found between the R group and the controls. CONCLUSION Prolonged malnutrition, but not weight recovery, is associated with an abnormal regional fat distribution pattern in moderately malnourished AN adolescents.

Comparative effects of teriparatide and strontium ranelate in the periosteum of iliac crest biopsies in postmenopausal women with osteoporosis.

The periosteum contains osteogenic cells that regulate the outer shape of bone and contribute to determine its cortical thickness, size and position. We assessed the effects of subcutaneous injections of teriparatide (TPTD, 20μg/day) or oral strontium ranelate (SrR, 2g/day) in postmenopausal women with osteoporosis on new bone formation activity at the periosteal and endosteal bone surfaces using dynamic histomorphometric measurements. Evaluable tetracycline-labeled transiliac crest bone biopsies were analyzed from 27 patients in the TPTD group, and 22 in the SrR group after six months of treatment. Measurements were conducted on the thicker and thinner cortices separately, and comparisons between the thicker, thinner and combined cortices were carried out. At the combined periosteal cortex, the mineralization surface as a percent of bone surface (MS/BS%) was greater for TPTD (mean±SE: 8.08±1.22%) than SrR (3.22±1.05%) (p<0.005). The difference in mineral apposition rate (MAR) between TPTD (0.35±0.06μm/day) and SrR (0.14±0.06μm/day) was also significant (p<0.05), while that of bone formation rate per bone surface (BFR/BS) between TPTD (0.014±0.004 mm(3)/mm(2)/year) and SrR (0.004±0.003 mm(3)/mm(2)/year) was not (p=0.057). Statistically significant differences between the two treatments were also observed for MS/BS%, BFR/BS, MAR and the double-labeled perimeter in the periosteum of the thicker, but not thinner, iliac crest cortices. The comparison between the thicker and thinner cortices of both periosteal and endosteal surfaces showed statistically significant differences for MAR and the double-labeled perimeter for TPTD treated women. There were no statistically significant differences in any bone formation dynamic measurements between the two cortices in the SrR group. In conclusion, most of the bone formation and mineralization variables were significantly higher for TPTD- than SrR-treated women at both the periosteal and endosteal combined cortices. The response to TPTD for dynamic bone formation measurements in the periosteal surface was greater for the thicker than thinner cortex, but this difference was not significant in SrR treated patients. This may reflect a greater ability of TPTD to enhance responsiveness of bone to the mechanical loading environment. These effects on bone formation may underlie the improvement in bone quality in patients with osteoporosis treated with TPTD.

Increased Leptin/Adiponectin Ratio and Free Leptin Index Are Markers of Insulin Resistance in Obese Girls during Pubertal Development

Background: Modifications in body fat in obese patients during puberty determine changes in adipokines that affect insulin sensitivity. Aims: We hypothesized that the leptin/adiponectin (L/A) ratio and free leptin index (FLI) are good markers of insulin resistance (IR) and total body fat (TBF) during pubertal development. Methods: A prospective study of 32 obese girls (OG) and age-matched control girls (CG) was performed. OG were divided into those that maintained a weight loss (WL) of >1 SD of initial body mass index (BMI) (WL group, n = 25) and those without WL (NWL group, n = 7). Oral glucose tolerance tests (OGTT) were performed to evaluate IR. Correlations of adipokines, L/A, and FLI with BMI, waist circumference, percentage of TBF (%TBF) and IR were performed over pubertal development. Results: The L/A ratio and FLI were increased in OG at baseline. Both indexes decreased in the WL group as puberty progressed, with no change in CG or NWL. In the WL group, a correlation between L/A and FLI with OGTT and %TBF, and L/A and homeostasis model assessment (HOMA) was found throughout the study. Conclusion: The L/A ratio and FLI are good markers to follow changes in IR and %TBF after WL during puberty. Insulin more accurately reflects the changes in IR than HOMA.

Regional Skeletal Bone Deficit in Female Adolescents with Anorexia Nervosa: Influence of the Degree of Malnutrition and Weight Recovery in a Two Year Longitudinal Study

AIM To analyze changes in bone mineral density (BMD) and the effect of weight recovery on the restoration of bone mass in adolescent females with anorexia nervosa (AN) with moderate malnutrition. STUDY DESIGN We evaluated lumbar and femoral BMD in 27 females with restrictive AN with malnutrition and amenorrhea for over (M+PA) or less than (M+SA) one year and 12 with normal nutrition and amenorrhea for over one year (N+PA) followed for 24 months. RESULTS BMI remained below -1.5 SD in M+PA and increased at 24 months in M+SA. M+PA had low lumbar and femoral neck BMD at diagnosis, decreasing at 24 months. Lumbar BMD in N+PA and M+SA was reduced, with an increase in M+SA at 24 months. CONCLUSIONS Moderate malnutrition in AN induces loss of bone mass at the lumbar and femoral levels. Weight gain and resumption of menses increases bone mass, especially in the lumbar spine.

Factores clínicos asociados a la pérdida de masa ósea previa al trasplante cardíaco

Fundamento La prevalencia de osteoporosis es elevada en los pacientes sometidos a trasplantecardiaco antes y despues de este. Sin embargo, los factores clinicos implicados en esta perdidaprevia no son bien conocidos. El objetivo ha sido estudiar la densidad mineral osea (DMO) enpacientes pretrasplante cardiaco analizando factores clinicos y bioquimicos en relacion con lamasa osea. Pacientes y MeTodos Hemos estudiado la DMO en la columna lumbar y la cadera en 51 pacientescandidatos al trasplante cardiaco, evaluando el grado funcional de la cardiopatia, el tiempode evolucion, los parametros antropometricos y los marcadores bioquimicos del remodeladooseo. La DMO de la columna lumbar y la cadera fueron medidas mediante densitometria dualde rayos X. Resultados Se encontro una disminucion significativa en la masa osea lumbar y en la caderaen los pacientes en relacion con la poblacion normal. La prevalencia de osteoporosis fue elevada(27,4%). El tiempo de espera fue la variable que mas influyo sobre la perdida osea de estospacientes en el hueso trabecular (columna lumbar). No se encontraron alteraciones en los parametrossistematicos de sangre y del metabolismo mineral, asi como en la PTH intacta serica.Los marcadores sericos de resorcion estaban aumentados frente a los de formacion, que resultaronnormales, indicando una osteoporosis de recambio incrementado. El efecto protector dela masa corporal se asocio a una menor perdida osea, respecto a los pacientes con osteoporosis,con un indice de masa corporal significativamente menor. Los pacientes con osteoporosistambien tenian un mayor tiempo de evolucion de su cardiopatia pretrasplante cardiaco. Conclusiones En los pacientes con insuficiencia cardiaca existe antes del trasplante cardiacouna menor masa osea en la columna lumbar y la cadera, con una mayor prevalencia de osteoporosis.El tiempo de espera pretrasplante cardiaco ha sido un factor importante en el desarrollode la enfermedad metabolica osea de estos pacientes.

Acylated ghrelin levels in pre-pubertal obese children at diagnosis and after weight reduction: Effect of oral glucose ingestion

Background: Ghrelin isoforms are involved in energy homeostasis and carbohydrate metabolism. Aim: To determine the influence of oral glucose ingestion and weight reduction on acylated ghrelin (AG) serum levels and on the AG to total ghrelin (TG) ratio (AG/TGr) in obese pre-pubertal children. Subjects and methods: Seventy obese children were studied at diagnosis (D) and after reduction of their body mass index (BMI) of over 1 (−1; no.=51) and 2 SD score (−2; no.=21). Body composition was analyzed and serum levels of glucose, insulin, TG and AG, and the AG/TGr were determined at every time-point in an oral glucose tolerance test (OGTT) at D and at −2. The control group consisted of 32 lean children. Results: At D AG and TG levels were lower in obese children and negatively correlated with BMI. TG levels were negatively correlated with the homeostasis model assessment (HOMA) index in the whole cohort, as with the body fat content (BFC) in the obese patients. Weight loss exclusively reduced BFC and improved HOMA, increasing AG transiently and TG sustainedly, with AG/TGr exclusively decreasing at −2. Glucose ingestion caused a sustained increase in AG and decrease in TG, thus increasing the AG/TGr throughout the entire OGTT; this remained unaltered after weight reduction. Conclusions: TG and AG levels are influenced by BMI, showing an impairment in childhood obesity that can be improved through weight loss. The different fractions of ghrelin appear to play different roles in carbohydrate metabolism and the calculation of AG/TGr could be useful in the follow up of childhood obesity.