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1.
Clin Endocrinol (Oxf) ; 95(1): 58-64, 2021 07.
Article in English | MEDLINE | ID: mdl-33559169

ABSTRACT

OBJECTIVE: Acromegaly is associated with increased vertebral fracture (VFs) risk not correlated to bone mineral density (BMD). Trabecular bone score (TBS), related to bone microarchitecture, provides information on bone strength. This cross-sectional study considered the usefulness of TBS and BMD to assess bone status in long-term controlled acromegalic patients. DESIGN, PATIENTS, MEASUREMENTS: 26 acromegaly patients (14 female and 12 males) were included in the study. A further 117 subjects were recruited as controls (58 females and 57 males). BMD was measured using dual-energy X-ray absorptiometry (DXA), TBS was obtained applying Medimaps software 2.0. Biochemical parameters were determined by standardized techniques. RESULTS: 73% of patients with acromegaly exhibited normal lumbar spine (LS) BMD. TBS was normal in 38% of acromegalic patients and partially degraded or degraded in 31% of patients, respectively. No differences were found in LS BMD between acromegalic patients and controls. TBS values were significantly lower in patients with acromegaly (1.27 ± 0.13 vs. 1.35 ± 0.17, p = .01). Postsurgical remission was associated with higher TBS values (1.35 ± 0.10 vs. 1.23 ± 0.13, p = .02) and pituitary radiotherapy treatment with lower TBS values (1.18 ± 0.12 vs. 1.31 ± 0.12, p = .004). On multivariate analysis, age, BMI and LS BMD were predictors of TBS changes in patients with acromegaly (p < .05). CONCLUSIONS: Patients with long-term controlled acromegaly can exhibit deterioration of bone microstructure measured with TBS, despite BMD measurement not showing bone loss. Our study suggests that TBS is useful for monitoring the bone status changes in acromegalic patients.


Subject(s)
Acromegaly , Osteoporotic Fractures , Absorptiometry, Photon , Acromegaly/complications , Bone Density , Cancellous Bone/diagnostic imaging , Cross-Sectional Studies , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male
2.
Front Pediatr ; 8: 551103, 2020.
Article in English | MEDLINE | ID: mdl-33163464

ABSTRACT

Background: Body fat content and distribution in childhood is influenced by sex and puberty, but interethnic differences in the percentage and distribution of body fat also exist. The abdominal visceral/subcutaneous fat ratio has been the main feature of body fat distribution found to associate with the serum adipokine profile and metabolic derangement in adulthood obesity. This has also been assumed for childhood obesity despite the known singularities of this disease in the pediatric age in comparison to adults. Objective: We aimed to investigate the effect of ethnicity, together with sex and pubertal status, on body fat content and distribution, serum adipokine profile, metabolic impairment and liver steatosis in children and adolescents with obesity. Patients and Methods: One hundred and fifty children with obesity (50% Caucasians/50% Latinos; 50% males/50% females) were studied. Body fat content and distribution were studied by whole body DXA-scan and abdominal magnetic resonance, and their relationships with liver steatosis (as determined by ultrasonography), glycemia, insulinemia, lipid metabolism, uric acid, total and HMW-adiponectin, leptin, leptin-receptor, and sex steroid levels were explored. Results: Latino patients had more severe truncal obesity (higher trunk/lower limb fat ratio, odds ratio 10.00; p < 0.05) and higher prevalence of liver steatosis than Caucasians regardless of sex or pubertal status, but there were no difference in the visceral/subcutaneous abdominal fat ratio, except for pubertal females. A higher trunk/lower limb fat ratio, but not the visceral/subcutaneous abdominal fat ratio, was associated with adipokine profile impairment (higher free leptin index and lower adiponectin levels), insulin resistance and dyslipidemia, and was further enhanced when liver steatosis was present (p < 0.05). A higher abdominal visceral/subcutaneous fat ratio was observed in prepubertal children (p < 0.01), except for Latino females, whereas predominant subcutaneous fat deposition was observed in adolescents. Conclusion: Ethnicity is one of the main determinants of increased trunk body fat accumulation in Latino children with obesity, which is best estimated by the trunk/lower limb fat ratio and related to the development of metabolic derangement and liver steatosis.

4.
Int J Cancer ; 146(2): 521-530, 2020 01 15.
Article in English | MEDLINE | ID: mdl-31403184

ABSTRACT

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.


Subject(s)
Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Heterogeneous-Nuclear Ribonucleoprotein Group F-H/genetics , MicroRNAs/metabolism , Thyroid Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Alternative Splicing/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Disease-Free Survival , Female , Follow-Up Studies , Gene Expression Profiling , Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Signal Transduction/genetics , Survival Rate , Thyroid Gland/pathology , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathology
6.
J Clin Endocrinol Metab ; 101(11): 3879-3883, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27648969

ABSTRACT

CONTEXT: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established. CASE DESCRIPTION: A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 µg/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment. CONCLUSION: Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency.


Subject(s)
Frameshift Mutation , Growth Disorders/drug therapy , Insulin-Like Growth Factor I/therapeutic use , Pregnancy-Associated Plasma Protein-A/deficiency , Child , Codon, Terminator , Exons , Female , Growth Disorders/genetics , Homozygote , Humans , Insulin-Like Growth Factor I/administration & dosage , Insulin-Like Growth Factor I/adverse effects , Insulin-Like Growth Factor I/genetics , Male , Pregnancy-Associated Plasma Protein-A/genetics , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Siblings , Treatment Outcome
7.
Ther Adv Endocrinol Metab ; 7(3): 93-100, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27293538

ABSTRACT

BACKGROUND: Adult growth hormone deficiency (AGHD) is characterized by impaired physical activity, diminished quality of life (QoL), weight and fat mass gain, decreased muscle mass and decreased bone mineral density (BMD). The aim of this study was to evaluate the effects of long-term treatment (7 years) with recombinant human growth hormone (rhGH) on metabolic parameters, body composition (BC), BMD, bone microarchitecture and QoL. PATIENTS AND METHODS: In this prospective study, BMD and BC were assessed by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture was assessed with the trabecular bone score (TBS). The QoL-AGHDA test was used to assess QoL. RESULTS: A total of 18 AGHD patients (mean age, 37.39 ± 12.42) were included. Body weight and body mass index (BMI) showed a significant increase after 7 years (p = 0.03 and p = 0.001, respectively). There was a significant tendency of body fat mass (BFM) (p = 0.028) and lean body mass (LBM) (p = 0.005) to increase during the 7 years of rhGH treatment. There was a significant increase in lumbar spine (LS) BMD (p = 0.01). TBS showed a nonsignificant decrease after 7 years of treatment, with a change of -0.86% ± 1.95. QoL showed a large and significant improvement (p = 0.02). CONCLUSION: Long-term rhGH treatment in AGHD patients induces a large and sustained improvement in QoL. Metabolic effects are variable with an increase in LBM as well as in BMI and BFM. There is a positive effect on BMD based on the increase in LS BMD, which stabilizes during long-term therapy and is not associated with a similar increase in bone microarchitecture.

8.
EMBO Mol Med ; 8(4): 363-74, 2016 04 01.
Article in English | MEDLINE | ID: mdl-26902202

ABSTRACT

Mutations in multiple genes of the growth hormone/IGF-I axis have been identified in syndromes marked by growth failure. However, no pathogenic human mutations have been reported in the six high-affinity IGF-binding proteins (IGFBPs) or their regulators, such as the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) that is hypothesized to increase IGF-I bioactivity by specific proteolytic cleavage of IGFBP-3 and -5. Multiple members of two unrelated families presented with progressive growth failure, moderate microcephaly, thin long bones, mildly decreased bone density and elevated circulating total IGF-I, IGFBP-3, and -5, acid labile subunit, and IGF-II concentrations. Two different homozygous mutations in PAPPA2, p.D643fs25* and p.Ala1033Val, were associated with this novel syndrome of growth failure. In vitro analysis of IGFBP cleavage demonstrated that both mutations cause a complete absence of PAPP-A2 proteolytic activity. Size-exclusion chromatography showed a significant increase in IGF-I bound in its ternary complex. Free IGF-I concentrations were decreased. These patients provide important insights into the regulation of longitudinal growth in humans, documenting the critical role of PAPP-A2 in releasing IGF-I from its BPs.


Subject(s)
Dwarfism/genetics , Insulin-Like Growth Factor Binding Proteins/metabolism , Insulin-Like Growth Factor I/metabolism , Mutation , Pregnancy-Associated Plasma Protein-A/genetics , Pregnancy-Associated Plasma Protein-A/metabolism , Adolescent , Child , Child, Preschool , Dwarfism/pathology , Female , Humans , Longitudinal Studies , Male , Young Adult
9.
Transpl Int ; 29(3): 331-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26615002

ABSTRACT

The aim of this study was to analyse the effect of risedronate on Trabecular Bone Score in liver transplant patients with low bone mass, during 1-year follow-up. In this retrospective cohort study, trabecular bone score (TBS) was calculated from dual X-ray absorptiometry images of the lumbar spine (LS), collected from a prospective randomized open-label 1-year trial performed in liver recipient patients. A total of 89 patients with osteopenia or osteoporosis were randomized to receive RIS plus calcium and vitamin D3 or calcium and vitamin D3. TBS was low in both groups at baseline, 6 and 12 months. Baseline TBS at the LS showed degraded microarchitecture in 22.8% of patients, partially degraded in 40.3%, and normal values in 36.8% of the patients. After 1 year of treatment, no difference in TBS was observed between both groups. No correlations were found between bone mineral density (BMD) and TBS values at any follow-up time point. No relationship was found between BMD, TBS or immunosuppressive drugs with incidental fracture. No significant effect in TBS was observed in liver transplant patients treated with RIS or calcium and vitamin D3 after 1 year of follow-up. In these patients, the clinical usefulness of this new tool should be established.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Liver Transplantation , Osteoporosis/drug therapy , Postoperative Complications/drug therapy , Risedronic Acid/therapeutic use , Aged , Bone Density Conservation Agents/pharmacology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risedronic Acid/pharmacology
10.
Endocrine ; 44(3): 803-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23536284

ABSTRACT

Erythropoietic protoporphyria (EPP) is a rare disease with painful cutaneous photosensitivity, in which patients are recommended to avoid sun exposure, and wear sunscreen and adequate clothing. Our aim was to study bone mineral density (BMD) and other mineral parameters, including serum 25(OH)D levels, to evaluate the impact of these measures in the follow-up of EPP patients. A cross-sectional study of ten EPP patients (median age 25; range 22-55, four males and six females), was performed evaluating clinical features, biochemical values (bone markers and serum 25 hydroxyvitamin D), and BMD. Median serum 25(OH)D level was 19.65 ng/ml [17.50; 24.80]. Four patients had 25(OH)D in insufficiency range (20-30 ng/ml) and five patients in the deficiency range (<20 ng/ml). Lumbar T-score median levels were in the osteopenia range in both females (-1.50 [-2.30; -1.0]) and males (-1.90 [-2.40; -0.70]). Also, in the female group median femoral neck T-score were in the osteopenia range (-1.20 [-1.60; -0.60]). This is the first study reporting low BMD in EPP patients. Osteoporosis, osteopenia, and vitamin D deficiency are frequent findings in EPP patients. The contribution of sunlight avoidance measures to these results remains to be clarified. Serum levels of protoporphyrins were not related to these alterations and other factors should be investigated. We suggest that the monitoring of serum vitamin D levels in EPP patients should be mandatory, as well as vitamin D and calcium supplementation.


Subject(s)
Bone Density/physiology , Femur Neck/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Protoporphyria, Erythropoietic/blood , Protoporphyria, Erythropoietic/diagnostic imaging , Vitamin D/analogs & derivatives , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Radiography , Vitamin D/blood
11.
J Bone Miner Res ; 28(6): 1355-68, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23322362

ABSTRACT

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.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Etidronic Acid/analogs & derivatives , Glucocorticoids/adverse effects , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Teriparatide/administration & dosage , Adult , Aged , Aged, 80 and over , Bone Density/drug effects , Bone Density Conservation Agents/adverse effects , Etidronic Acid/administration & dosage , Europe , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/metabolism , Middle Aged , Osteoporosis/diagnostic imaging , Osteoporosis/metabolism , Radiography , Risedronic Acid , Spinal Fractures/diagnostic imaging , Spinal Fractures/metabolism
12.
Prog Transplant ; 22(3): 237-43, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22951500

ABSTRACT

OBJECTIVE: To compare the effects of calcitonin, etidronate, and alendronate in preventing bone loss during the first 2 years after heart transplant. METHODS: A total of 222 heart transplant recipients (mean [SD] age, 52.4 [10] years, 85% male) were evaluated. Patients with normal bone mineral density (reference group, n = 102) received 1000 mg/d calcium plus 800 IU/d vitamin D3. The rest were assigned to 200 IU/d of calcitonin (n=42), 400 mg/d etidronate orally for 14 days quarterly (n = 33), or 10 mg/d alendronate (n = 45). All patients received calcium and vitamin D. Bone mineral density was assessed by dual-energy x-ray absorptiometry in the lumbar spine, the entire femur, and the femoral neck at baseline and 6, 12, and 24 months after transplant. RESULTS: At 2 years after transplant, bone mineral density in the lumbar spine had decreased in the reference group (-3.07%), calcitonin group (-0.93%), and etidronate group (-1.87%) but not in the alendronate group (+4.9%; P <.001). After 2 years, bone mineral density in the entire femur decreased in all groups (-3.2% in the reference group, -3.6% in the calcitonin group, -4.6% in the etidronate group, and -0.5% in the alendronate group) but bone loss was significantly lower in the alendronate group (P <.001). Bone mineral density in the femoral neck also decreased in all groups. The incidence of vertebral fractures did not differ among groups. Adverse events were similar between groups. CONCLUSIONS: Alendronate therapy in heart transplant recipients was associated with a significant increase in bone mineral density in the lumbar spine and less bone loss at the hip.


Subject(s)
Alendronate/therapeutic use , Bone Demineralization, Pathologic/etiology , Bone Demineralization, Pathologic/prevention & control , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Calcitonin/therapeutic use , Calcium/therapeutic use , Etidronic Acid/therapeutic use , Heart Transplantation/adverse effects , Vitamin D/therapeutic use , Absorptiometry, Photon , Adolescent , Adult , Aged , Analysis of Variance , Chi-Square Distribution , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Treatment Outcome
15.
J Bone Miner Res ; 27(3): 687-93, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22095631

ABSTRACT

Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < -4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Fractures, Bone/prevention & control , Spinal Fractures/prevention & control , Absorptiometry, Photon , Aged , Aged, 80 and over , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Bone Density Conservation Agents/pharmacology , Denosumab , Double-Blind Method , Female , Fractures, Bone/pathology , Humans , Middle Aged , Placebos , Risk Reduction Behavior , Spinal Fractures/pathology
16.
Transpl Int ; 24(7): 657-65, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21466595

ABSTRACT

The aim of this study was to investigate the effect of risedronate (RIS) on bone loss and bone turnover markers after liver transplantation (LT). Patients with osteopenia or osteoporosis within the first month after LT were randomized to receive RIS 35 mg/week plus calcium 1000 mg/day and vitamin D(3) 800 IU/day (n = 45) or calcium and vitamin D(3) at same dosages (n = 44). Primary endpoint was change in bone mineral density (BMD) 6 and 12 months after LT. Secondary endpoints included changes in serum ß-CrossLaps (ß-CTX) and procollagen type 1 amino-terminal peptide (P1NP) and fracture rate. Spine X-rays were obtained at baseline and after 12 months. There was no significant difference in BMD changes between both treatment groups at any sites; either at 6 or 12 months. Spine BMD increased in both groups at 12 months vs. baseline (P = 0.001). RIS patients had a significant increase in intertrochanteric BMD at 12 months (P < 0.05 vs. baseline). Serum ß-CTX decreased in both groups (P < 0.01), with significant differences between groups at 3 months. No significant difference in vertebral fracture incidence was found. After 12 months, BMD improved at lumbar spine and did not change at hip in both groups. Significant differences between both groups were not found. Other factors (calcium and vitamin D replacement, early prednisone withdrawal) seem to have also positive effects in BMD.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Remodeling/drug effects , Etidronic Acid/analogs & derivatives , Liver Transplantation/adverse effects , Adult , Calcium/therapeutic use , Cholecalciferol/therapeutic use , Etidronic Acid/therapeutic use , Female , Humans , Male , Middle Aged , Postmenopause , Prospective Studies , Risedronic Acid , Spinal Fractures/prevention & control
17.
Bone ; 48(5): 972-8, 2011 May 01.
Article in English | MEDLINE | ID: mdl-21262402

ABSTRACT

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.


Subject(s)
Ilium/drug effects , Organometallic Compounds/pharmacology , Organometallic Compounds/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Periosteum/drug effects , Teriparatide/pharmacology , Teriparatide/therapeutic use , Thiophenes/pharmacology , Thiophenes/therapeutic use , Biopsy , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use , Female , Humans , Ilium/pathology , Osteoporosis, Postmenopausal/pathology , Periosteum/pathology
18.
Obesity (Silver Spring) ; 18(12): 2288-94, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20339359

ABSTRACT

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.


Subject(s)
Adiponectin/blood , Body Mass Index , Obesity/blood , Weight Loss/physiology , Absorptiometry, Photon , Adipose Tissue/physiology , Case-Control Studies , Child , Female , Humans , Insulin Resistance , Interleukin-6/blood , Leptin/blood , Male , Obesity/therapy , Reference Values , Tumor Necrosis Factor-alpha/blood , Weight Gain/physiology
19.
Endocrinol Nutr ; 56(4): 164-9, 2009 Apr.
Article in Spanish | MEDLINE | ID: mdl-19627732

ABSTRACT

BACKGROUND AND OBJECTIVES: Recent studies have shown a high frequency of insufficient serum vitamin D levels in the general population, especially in the elderly and in individuals with osteoporosis. Data from the young adult population are scarce, but also reveal a high prevalence of vitamin D insufficiency and deficiency in this age group. The main reasons for this high prevalence seem to be poor dietary vitamin D intake and low sun exposure. The aim of the present study was to determine the prevalence of vitamin D insufficiency and deficiency in a young healthy population and its association with concentrations of calcium and parathyroid hormone and sun exposure. METHODS: We performed an observational, descriptive study in 116 subjects (38 men and 78 women aged 26.56 +/- 3.32 years), during the late spring and early summer of 2007. Fasting blood samples were obtained and levels of 25-hydroxivitamin D, intact parathyroid hormone, calcium, albumin and creatinine were measured. A questionnaire designed to assess sun exposure and sunshine protection during the previous 12 months was administered. RESULTS: The mean value of 25-hydroxivitamin D obtained was 24.58 +/- 6.98 ng/ml. The subjects were divided into three groups according to 25-hydroxivitamin D levels: deficient: < 20 ng/ml (27.58%); insufficient: 20-30 ng/ml (56.03%); and sufficient: > or = 30 ng/ml (16.37%). No statistically significant differences were found between the groups or the studied variables except for age in relation to vitamin D levels. CONCLUSIONS: Our study shows a high prevalence of vitamin D insufficiency in a young healthy population with no clear relationship with sun exposure or sunscreen protection. The low intake of food rich in vitamin D and the lack of food fortification combined with scarce effective sun exposure could account for the low serum levels of vitamin D in this population.


Subject(s)
Vitamin D Deficiency/epidemiology , Adult , Calcium/blood , Creatinine/blood , Diet , Dietary Supplements , Drug Utilization/statistics & numerical data , Environmental Exposure , Female , Humans , Male , Parathyroid Hormone/blood , Personnel, Hospital/statistics & numerical data , Prevalence , Serum Albumin/analysis , Spain/epidemiology , Sunlight , Sunscreening Agents , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/etiology , Young Adult
20.
Endocrinol Nutr ; 56(5): 262-4, 2009 May.
Article in Spanish | MEDLINE | ID: mdl-19627747

ABSTRACT

Many problems may arise when defining whether adrenal lesions are primary to the adrenal glands or represent other tissue, whether they are benign or malignant and whether they are functioning or nonfunctioning. Adrenal imaging complements the clinical and hormonal evaluation of these patients. We present a patient with lumbar pain and bilateral adrenal masses.


Subject(s)
Adrenal Gland Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/secondary , Low Back Pain/etiology , Lung Neoplasms/pathology , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/diagnosis , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Biopsy, Fine-Needle , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/diagnosis , Humans , Low Back Pain/drug therapy , Lung Neoplasms/diagnosis , Male , Palliative Care , Smoking/adverse effects , Tomography, X-Ray Computed
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