Esteban Jódar

Prevalencia de concentraciones deficientes e insuficientes de vitamina D en una población joven y sana

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: 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.

Bone mineral density and risk of fractures in aging, obese post-menopausal women with type 2 diabetes. The GIUMO Study.

Background and aims: Type 2 diabetes mellitus (DM) has a high prevalence in aging obese postmenopausal women. It is not clear whether or not diabetes produces an increase in bone mineral density or an increase in fracture rates. Objective: The main objective of this study was to investigate whether type 2 DM produces a higher prevalence of vertebral, hip and non-vertebral fractures in obese postmenopausal Caucasian women. A secondary objective was to study the influence of DM in quantitative ultrasound measurements of the heel (QUS) and bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), in both lumbar spine (L2–L4) and proximal femur. Method: This study was a prospective cohort of 111 patients with type 2 DM and 91 control individuals (CTR) over age 65 and obese, recruited from 16 centers in Spain. Main Outcome Measures: Lateral dorsal and lumbar X-rays were performed to assess vertebral fractures. Hip and non-vertebral fractures were noted from medical records, written reports or X-ray studies. QUS measurements were made of the calcaneus and BMD measurements of the lumbar spine (L2–L4) and proximal femur. Results: Patients had higher BMD in the lumbar spine (L2–L4) than controls (0.979 g/cm2 vs 0.927 g/cm2, p=0.035), but we found no statistically significant differences in the proximal femur. QUS measurements showed similar values in both groups: BUA (69.3 dB/Mhz vs 66.7 dB/Mhz, p=0.291), SOS (1537 m/sg vs 1532 m/sg, p=0.249) and QUI (87.5 vs 83.7, p=0.153). No statistically significant differences were found in any case. There was no association between vertebral, hip and non-vertebral fractures and DM. The crude odds ratio, without adjusting was 1.045 (CI 957o 0.531; 2.059), and the adjusted odds ratio was 0.927 (CI 95% 0.461; 1.863). Conclusions: In obese postmenopausal Caucasian women, type 2 DM produces an increase in BMD of the lumbar spine without changes in BMD of the proximal femur or in QUS measurements of the heel. The prevalence of vertebral, hip and non-vertebral fractures did not increase in type 2 DM.

Long-Term Follow-up of Bone Mass after Orthotopic Liver Transplantation: Effect of Steroid Withdrawal from the Immunosuppressive Regimen

Abstract: Glucocorticoids have been suggested to play a major role in transplantation-related osteopenia. In this study we assess the long-term changes and the effect of steroid withdrawal from the standard immunosuppressive regimen on bone mineral density (BMD) after orthotopic liver transplantation (OLT). Sixty-nine non-osteoporotic patients (20 women, 49 men), aged 48 ± 9.5 years (mean ± SD), and with a follow-up of 58.3 ± 23.2 months (range 24–121 months) were studied. Immunosuppressive treatment consisted of prednisone, cyclosporin A and azathioprine. In 41 patients (group A), prednisone was tapered and withdrawn after 36.2 ± 19.3 months (range 13–79 months), whereas in 28 patients (group B) prednisone was maintained. BMD in the spine (L1–L4) was serially measured by dual-energy X-ray absorptiometry (Hologic QDR 1000w) at baseline, before steroid withdrawal and at the end of study. Age- and sex-matched Z-scores of BMD were calculated. No differences were found in age, body mass index, time since OLT, or baseline BMD between the two groups. BMD had significantly increased in both groups at the end of follow-up period (group A, +8.1 ± 8.7%; group B, +3.2 ± 8.0%, p<0.05). However, the Z-score was significantly higher in group A than in group B at the end of study (–0.44 ± 1.05 vs –0.99 ± 0.77; p<0.05). BMD recovery was lower in pre-OLT biliary cirrhosis patients. Bone mass improvement was independent of the time since OLT in both groups, and of the time of steroid withdrawal in group A. Our data confirm that steroid withdrawal accelerates the recovery of bone mass in patients who have undergone a successful liver transplantation.

Placebo‐controlled, randomized trial of the addition of once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD‐9)

To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub‐optimum glycated haemoglobin (HbA1c) concentration.

Bone Mass, Bone Turnover, Vitamin D, and Estrogen Receptor Gene Polymorphisms in Male to Female Transsexuals: Effects of Estrogenic Treatment on Bone Metabolism of the Male

The effect of chronic administration of estrogens on bone and mineral metabolism in men is not known. We have studied the effect of chronic administration of estrogens on bone mineral metabolism in a group of transsexual (TS) Canarian men, who were taking estrogens for a minimum of 3 years. This is a cross-sectional study of cases and controls and we studied biochemical markers of bone remodeling, bone mineral density (BMD), and selected biochemical and hormonal features. TS subjects had shorter stature than controls, and after adjusting for height and weight, we found that they had lower values for serum-free testosterone and higher values for BMD, both in the lumbar spine and in femoral neck. Biochemistry, bone remodeling markers, and calcitropic hormone values were similar in both groups. Finally, the distributions of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba) polymorphisms were also similar in both groups. We conclude that the chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD-both in lumbar spine and in femoral neck. We found no association between the transsexual phenotype and the distribution of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba).

Postmenopausal Canarian women receiving oral glucocorticoids have an increased prevalence of vertebral fractures and low values of bone mineral density measured by quantitative computer tomography and dual X-ray absorptiometry, without significant changes in parathyroid hormone

BACKGROUND Daily doses higher than 7.5 mg/daily of prednisone or equivalents confer a great risk of vertebral and hip fractures with a clear dose dependence of fracture risk. Information regarding the utility in assessing trabecular bone mineral density by quantitative computer tomography (QCT) in these patients, either in the Canaries or in Spain, is lacking. Moreover, in this setting, the importance of secondary hyperparathyroidism is still controversial. DESIGN, PATIENTS AND METHODS Cross-sectional observational study performed on 1177 consecutive Canary postmenopausal women who attended our Bone Metabolic Unit. The Patient Group was composed of 88 postmenopausal women who were taking oral corticosteroids in dose higher than 7.5 mg/day of prednisone or equivalent for more than 6 months (OG group). The Control Group included 838 postmenopausal women who did not take steroids. A complete validated questionnaire for osteoporosis risk assessment and a complete physical examination were performed. A lateral X-ray of the spine was performed on every woman. Bone mineral density (BMD) was measured at the lumbar spine (LS) by dual X-ray Absorptiometry (DXA) and QCT and at the femoral neck by DXA. Fasting serum and 24 hour urine was collected and biochemical markers of bone remodelling were studied. RESULTS Both groups were comparable in general characteristics and calcium intake. The OG group showed lower values of BMD estimated both by DXA and QCT (p<0.05). LS BMD was closely correlated by using both methods (r=0.636, p<0.001). The OG group showed lower values of osteocalcin (p=0.023) and TRAP (p=0.026) without significant differences in PTH. Patients in OG group had a higher prevalence of vertebral fractures than controls (13.3% vs 8.6%; crude values: p=0.049, OR: 1.63 (0.99-2.67); age adjusted: p=0.003, OR 2.29 (1.33-9.93)). CONCLUSIONS In postmenopausal Canarian women, chronic glucocorticoid therapy is associated with low bone mineral density, measured either by DXA or QCT, with evidence of low turnover and high prevalence of fractures without significant changes in PTH. DXA and QCT provide similar information in the assessment of this high risk population.

Efficacy and Safety of IDegLira Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Uncontrolled on Metformin and Basal Insulin: The DUAL VII Randomized Clinical Trial

OBJECTIVE In patients with uncontrolled type 2 diabetes on basal insulin, prandial insulin may be initiated. We assessed the efficacy and safety of initiating insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus basal-bolus insulin. RESEARCH DESIGN AND METHODS A phase 3b trial examined patients with uncontrolled type 2 diabetes on insulin glargine (IGlar U100) 20–50 units/day and metformin, randomized to IDegLira or IGlar U100 and insulin aspart ≤4 times per day. RESULTS Glycated hemoglobin (HbA1c) decreased from 8.2% (66 mmol/mol) to 6.7% (50 mmol/mol) with IDegLira and from 8.2% (67 mmol/mol) to 6.7% (50 mmol/mol) with basal-bolus (estimated treatment difference [ETD] −0.02% [95% CI −0.16, 0.12]; −0.2 mmol/mol [95% CI −1.7, 1.3]), confirming IDegLira noninferiority versus basal-bolus (P < 0.0001). The number of severe or blood glucose–confirmed symptomatic hypoglycemia events was lower with IDegLira versus basal-bolus (risk ratio 0.39 [95% CI 0.29, 0.51]; rate ratio 0.11 [95% CI 0.08, 0.17]). Body weight decreased with IDegLira and increased with basal-bolus (ETD −3.6 kg [95% CI −4.2, −2.9]). Fasting plasma glucose reductions were similar; lunch, dinner, and bedtime self-monitored plasma glucose measurements were significantly lower with basal-bolus. Sixty-six percent of patients on IDegLira vs. 67.0% on basal-bolus achieved HbA1c <7.0% (53 mmol/mol). Total daily insulin dose was lower with IDegLira (40 units) than basal-bolus (84 units total; 52 units basal). CONCLUSIONS In patients with uncontrolled type 2 diabetes on IGlar U100 and metformin, IDegLira treatment elicited HbA1c reductions comparable to basal-bolus, with statistically superior lower hypoglycemia rates and weight loss versus weight gain.

Bone loss after heart transplant: effect of alendronate, etidronate, calcitonin, and calcium plus vitamin D3

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.

Declaración española sobre la Vitamina D en el manejo de la osteoporosis

aCoordinador bAsociación Española Contra la Osteoporosis (AECOS) cAsociación Española para el Estudio de la Menopausia (AEEM) dFundación Hispana de Osteoporosis y Enfermedades Metabólicas Óseas (FHOEMO) eSociedad Española de Cirugía Ortopédica y Traumatología (SECOT) fSociedad Española de Endocrinología y Nutrición (SEEN) gSociedad Española de Investigaciones Óseas y Metabolismo Mineral (SEIOMM) jSociedad Española de Medicina Interna (SEMI) hSociedad Española de Medicina Rural y Generalista (SEMERGEN) iSociedad Española de Medicina de Familia y Comunitaria (SEMFYC) kSociedad Española de Reumatología (SER)

Características y tipos de agonistas del receptor de GLP-1. Una oportunidad más para la individualización terapéutica

Glucagon-like peptide 1 (GLP-1) is secreted from enteroendocrine L-cells in response to oral nutrient intake and elicits glucose-stimulated insulin secretion while suppressing glucagon secretion. Moreover slows gastric emptying –reducing postprandial glycemic excursions–, reduces body weight, systolic blood pressure and has beneficial effects in the cardiovascular and central nervous systems. Since the 1990s, the efficacy of GLP-1 in reducing blood glucose levels in type 2 diabetes (DM2) was well known. However, GLP-1 should be administered by chronic subcutaneous infusion because of the rapid cleavage by the enzyme dipeptidyl peptidase 4 (DPP-4). Hence, DPP-4 inhibitors –which increase pseudophysiologically endogenous GLP-1 levels– were developed. In addition, several GLP-1 receptor agonists have been designed to avoid DPP-4-breakdown and/or rapid renal elimination and, therefore, induce a pharmacologic effect in the GLP-1 receptor: short-acting, long-acting, and prolonged-acting GLP-1 analogs. Each class has different structural, pharmacodynamic and clinical properties and could be administered in different therapeutical regimens giving us the opportunity to individualize the therapy of DM2.