RESUMEN
Due to increasing life expectancy in thalassemia major (TM), osteoporosis is emerging as a significant problem. Its aetiology is multifactorial, culminating in increased bone resorption and impaired remodelling. Hypogonadism and marrow expansion seem to play an important role, but iron overload, deferoxamine toxicity, a defective growth hormone-insulin-like growth factor-1 axis and multiple endocrinopathies may represent additional causes of bone damage. Many of these patients, though under appropriate treatment programs, do not achieve normal peak bone mass. The receptor activator of nuclear factor kappa-ß (RANK)/RANK ligand/osteoprotegerin and the Wnt/ß-catenin systems work as major mediators of imbalanced bone turnover and bone loss. Additional genetic factors, such as collagen type 1 alpha 1 and vitamin D receptor gene polymorphisms, may exert some influence on the enhanced fracture risk observed in TM. To date, in spite of adequate hormone replacement, chelating therapy and acceptable haemoglobin levels, subjects with TM display impaired bone density and imbalanced bone turnover, thus the puzzle of the pathogenesis of TM-induced osteoporosis remains far from being solved.
Asunto(s)
Osteoporosis/patología , Talasemia beta/complicaciones , Humanos , Osteoporosis/etiología , PronósticoRESUMEN
BACKGROUND: Low vitamin D serum levels have been associated with unfavourable lipid profile and poorer response to atorvastatin. Aims of this study were to test the effects of 25-hydroxyvitamin D3 (calcifediol) compared to parental vitamin D3 (cholecalciferol) supplementation on modifications of plasma 25(OH)D levels and lipid profile. MATERIALS AND METHODS: Fifty-seven postmenopausal women (aged 59.03 ± 6.73 years) who were at low risk of fracture and with basal plasma 25(OH)D < 30 ng/mL were included if they were on atorvastatin treatment prescribed as appropriate. Recruited women were randomized to receive oral calcifediol or cholecalciferol, both at a dose of 140 µg according to a weekly regimen. RESULTS: At baseline, 25(OH)D was negatively associated with BMI (r = -0.37; P = 0.004), total cholesterol (r = -0.31; P = 0.01) and LDL-C (r = -0.32; P = 0.02). After 24 weeks, 25(OH)D increased significantly in both groups (P < 0.001), although higher levels were obtained with calcifediol as compared with cholecalciferol (P < 0.001). Only in the calcifediol group, a significant reduction of LDL-C (P = 0.01) and an increase of HDL-C (P = 0.02) were obtained, even after adjustment for age, and baseline BMI, 25(OH)D and lipid levels (P < 0.05). The percentage changes in 25(OH)D levels were associated with the variations of LDL-C (r = -0.44; P = 0.01) and HDL-C levels (r = 0.30; P = 0.10). CONCLUSION: Calcifediol administration in osteopenic and dyslipidemic postmenopausal women with low 25(OH)D improves lipid profile when added to an ongoing atorvastatin treatment.
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Calcifediol/administración & dosificación , Colecalciferol/administración & dosificación , Ácidos Heptanoicos/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Posmenopausia/efectos de los fármacos , Pirroles/administración & dosificación , Vitaminas/administración & dosificación , Administración Oral , Atorvastatina , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Suplementos Dietéticos , Quimioterapia Combinada , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Persona de Mediana Edad , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
BACKGROUND: Sclerostin is an osteocyte-derived inhibitor of the Wnt/ß-catenin signaling pathway, which acts as a negative regulator of bone formation. Published data on sclerostin levels in type 1 diabetes mellitus (T1DM) are few. OBJECTIVE: To evaluate gender differences in sclerostin serum levels and the association among sclerostin, bone mass, bone metabolism, and the main clinical characteristics of subjects with T1DM. DESIGN AND METHODS: A total of 69 patients with T1DM (mean age, 33.7±8.1; 49% males) were enrolled in this cross-sectional study in a clinical research center. Bone mineral density was measured by phalangeal quantitative ultrasound (QUS); bone turnover markers (urinary pyridinoline, deoxypyridinoline (D-PYR), and urine hydroxyproline (OH-PRO) to evaluate bone resorption; serum bone alkaline phosphatase and BGP to evaluate bone formation) and sclerostin were assessed. RESULTS: D-PYR and sclerostin were significantly higher in women when compared with men (P=0.04). A disease duration >15 years was associated with higher sclerostin levels (P=0.03). Bone turnover markers and QUS parameters were not correlated with sclerostin. A significant negative correlation was observed among QUS parameters, BMI, and OH-PRO. Sclerostin serum levels were correlated with homocysteine (r=-0.34, P=0.005) and vitamin B12 (r=-0.31, P=0.02). Generalized linear model showed that macroangiopathy was the only predictor of sclerostin serum levels (ß=-11.8, 95% CI from -21.9 to -1.7; P=0.02). CONCLUSIONS: Our data demonstrate that women with T1DM exhibit higher sclerostin levels than men and that circulating sclerostin is not associated with bone turnover markers and phalangeal QUS measurements. Macroangiopathy was associated with sclerostin levels.
Asunto(s)
Proteínas Morfogenéticas Óseas/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Caracteres Sexuales , Proteínas Adaptadoras Transductoras de Señales , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Marcadores Genéticos , Humanos , Masculino , Adulto JovenRESUMEN
CONTEXT: Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown. OBJECTIVE: The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers. DESIGN AND SETTING: We conducted a prospective intervention study in an ambulatory care setting. PARTICIPANTS AND INTERVENTION: Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo. MAIN OUTCOMES MEASURES: At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured. RESULTS: Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group. CONCLUSIONS: Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Proteínas Morfogenéticas Óseas/sangre , Huesos/efectos de los fármacos , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales , Anciano , Biomarcadores/sangre , Biomarcadores/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Regeneración Ósea/efectos de los fármacos , Resorción Ósea/etiología , Resorción Ósea/prevención & control , Huesos/metabolismo , Carbonato de Calcio/uso terapéutico , Colecalciferol/uso terapéutico , Colágeno Tipo I/sangre , Colágeno Tipo I/metabolismo , Terapia Combinada , Suplementos Dietéticos , Difosfonatos/administración & dosificación , Femenino , Marcadores Genéticos , Humanos , Imidazoles/administración & dosificación , Infusiones Intravenosas , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/dietoterapia , Osteoporosis Posmenopáusica/fisiopatología , Factor de Transcripción PAX5/sangre , Factor de Transcripción PAX5/metabolismo , Péptidos/sangre , Péptidos/metabolismo , Factores de Tiempo , Ácido ZoledrónicoRESUMEN
AIM: Heart failure (HF) and diabetes mellitus (DM) are each associated with cognitive impairment and disability. The aim of the present study was to evaluate the impact of DM on cognitive impairment and functional status in elderly hospitalized patients affected by HF. METHODS: A total of 79 elderly hospitalized patients with HF were enrolled in the present study. They underwent physical and instrumental examination, and geriatric multidimensional assessment including Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), activities of daily living (ADL) and instrumental activities of daily living (IADL). Differences between groups were established by t-test, Spearman's correlation coefficient was searched to examine the relation between variables. All results were considered significant if P was <0.05. RESULTS: HF and DM coexisted in 43 patients (54.4% of cases); when they occurred together patients showed, compared with non diabetic patients, a greater clinical severity of HF (44.2% were in New York Heart Association class IV vs 16.7%, P = 0.017), a lower MMSE score (20.4 ± 3.6 vs 23 ± 3.8, P = 0.004), and a lower number of preserved functions in ADL (3 ± 1.6 vs 4 ± 1.8, P = 0.008) and in IADL (3.2 ± 1.7 vs 4.6 ± 2.3, P = 0.003). The correlation between DM and cognitive impairment, and disability was confirmed by multivariate and univariate analysis. CONCLUSIONS: We confirm that DM is frequent in elderly hospitalized patients with HF, and we report that it has a negative impact on cognitive functions and functional status, worsening cognitive impairment, and disability observed in these patients. Comprehensive geriatric assessment is necessary for older adults with HF, especially when DM coexists.
Asunto(s)
Trastornos del Conocimiento/etiología , Complicaciones de la Diabetes/complicaciones , Insuficiencia Cardíaca/complicaciones , Actividades Cotidianas , Anciano , Personas con Discapacidad , Femenino , Hospitalización , Humanos , MasculinoRESUMEN
Osteoporosis is a major cause of fragility fractures and these are responsible of large social burden; nevertheless, osteoporosis often remains an underdiagnosed disease. FRAX is a new and simple validate fracture risk assessment tool helping physicians to select patients at high risk of future fragility fractures. To promote early diagnosis of osteoporosis, we evaluated fracture risk by FRAX and performed phalangeal quantitative ultrasound (QUS) measurements in a population of postmenopausal women referring to our center during the World Osteoporosis Day on 20th October 2011. Eighty post-menopausal women (age 60.8±8.6) were screened and the risk of major osteoporotic and hip fractures over ten years was calculated by considering multiple clinical risk factors (CRFs). The median risk of major osteoporotic fracture (%) was 4.9 (3.5-8.6) in women younger than 55 years, 7.3 (5.4-11) in women aged between 55 and 65 years and 17.5 (11-27) in women older than 65 years; the median risk of hip fracture (%) was 0.6 (0.3-1.3), 1.5 (0.9-2.5) and 7.2 (3.1-14) respectively. QUS measurements, were lower in the older women and when multiple CRFs coexisted, and were found to correlate with fracture risk, especially with hip fracture risk (p<0.05). Within one month from the screening, 75% (44/59) of the women over 55 years came back and received a diagnosis of osteoporosis/osteopenia by dual x-ray absorptiometry (DXA); a positive association between DXA and QUS measurements was observed (p<0.0001). Adequate treatment of these subjects could reduce fracture rates, improve the quality of life, and reduce the social costs of osteoporosis.
RESUMEN
The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000 IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5 mg) and received a daily supplementation of calcium (1,000 mg) and vitamin D (800 IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0 = no pain, 10 = unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P < 0.05] and exhibited lower inflammatory markers (P < 0.005 vs. placebo). Our data demonstrate that cholecalciferol at a dose of 300,000 IU reduces the intensity of musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Dolor Musculoesquelético/tratamiento farmacológico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Imidazoles/uso terapéutico , Persona de Mediana Edad , Dolor Musculoesquelético/fisiopatología , Osteoporosis Posmenopáusica/metabolismo , Proyectos Piloto , Estudios Prospectivos , Vitamina D/farmacología , Vitaminas/farmacología , Ácido ZoledrónicoRESUMEN
OBJECTIVES: To evaluate the role of genetic background in osteoporosis/osteopenia development in beta-Thalassemia Major patients. DESIGN AND METHODS: The influence of VDR (FokI, BsmI) as well as COLIA1 (Sp1) gene polymorphisms on BMD was investigated in 40 patients. RESULTS: Although the examined gene polymorphisms did not significantly affect BMD variations in our population, BsmI was found to display beneficial effects on patient response to alendronate therapy. CONCLUSION: Genetic factors retain a potential role for improvement of osteoporosis management in thalassemic patients.
Asunto(s)
Densidad Ósea/genética , Talasemia beta/genética , Adulto , Alendronato/uso terapéutico , Femenino , Humanos , Masculino , Polimorfismo Genético/genética , Talasemia beta/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate in a group of postmenopausal women the effects of long-term raloxifene treatment on breast density using a digitized analysis of mammograms and on insulinlike growth factor-1 (IGF-1), insulinlike growth factor binding protein-3 (IGFBP-3), and sex hormone-binding globulin (SHBG) plasma levels. DESIGN: Seventy healthy postmenopausal women with normal body weight were enrolled in this study and were divided into two groups based on their bone status, evaluated by dual-energy x-ray at the lumbar spine (L2-4). Fifty women (chronological age 52.4 +/- 4.1 y, menopausal age 42.1 +/- 3.9 y), in whom the L2-4 T score was less than -2.5 SD, were treated with raloxifene HCl 60 mg/day orally for 2 years. The other 20 women (chronological age 53.6 +/- 3.5 y, age at menopause 43.1 +/- 3.6 y), in whom the L2-4 T score ranged between -1 and -2.5 SD, were enrolled as controls. All 70 women received calcium (1 g/d orally) and cholecalciferol (880 UI/d orally) supplementation. Moreover, all women followed a normocaloric and personalized diet. All women had mammography at baseline and after 2 years of therapy. The mammographic images on traditional support (radiography) were acquired by using a film scanner and were then elaborated by means of ad hoc software. Moreover, assessments of IGF-1, IGFBP-3, and SHBG plasma levels were obtained at baseline and after 24 months. RESULTS: After 24 months of therapy, there was a significant variation in the raloxifene-treated group with respect to baseline in the distribution of gray classes of radiographic images. In particular, an attenuation of graphic trace with a reduction of the areas with the lowest and most elevated gray classes was observed. In the control group, no significant variations of graphic traces were observed. Moreover, raloxifene treatment significantly reduced IGF-1 and increased IGFBP-3 and SHBG plasma levels at 24 months. During follow-up, IGF-1, IGFPB-3, and SHBG levels did not change significantly in the control group. CONCLUSIONS: Long-term treatment with raloxifene in a population of postmenopausal women is able to reduce breast density. Such an effect could perhaps explain the reduction in the incidence of mammary carcinoma observed in the Multiple Outcomes of Raloxifene Evaluation study probably due to the direct antiestrogenic activity of raloxifene on mammalian tissue and/or its indirect activity increasing SHBG levels or modifying the IGF-1/IGFBP-3 ratio.
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Conservadores de la Densidad Ósea/farmacología , Mama/efectos de los fármacos , Posmenopausia , Clorhidrato de Raloxifeno/farmacología , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Absorciometría de Fotón , Adulto , Conservadores de la Densidad Ósea/administración & dosificación , Mama/patología , Neoplasias de la Mama/prevención & control , Estudios de Casos y Controles , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/efectos de los fármacos , Vértebras Lumbares , Mamografía , Persona de Mediana Edad , Clorhidrato de Raloxifeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Globulina de Unión a Hormona Sexual/efectos de los fármacosRESUMEN
In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.
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Anemia Sideroblástica/terapia , Trasplante de Médula Ósea , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/terapia , Cirrosis Hepática/terapia , Flebotomía , Adolescente , Anemia Sideroblástica/complicaciones , Anemia Sideroblástica/diagnóstico , Biomarcadores/sangre , Terapia por Quelación , Terapia Combinada , Deferiprona , Deferoxamina/uso terapéutico , Estudios de Seguimiento , Humanos , Sobrecarga de Hierro/complicaciones , Cirrosis Hepática/complicaciones , Masculino , Piridonas/uso terapéutico , Estudios RetrospectivosRESUMEN
The most devastating consequence of osteoporosis is bone fracture, particularly at the vertebral or femoral level. As defined by the WHO, patients with osteoporosis who have had one or more fragility fractures have severe osteoporosis. Those who sustain a vertebral fracture represent a particularly vulnerable group whose risk of another vertebral fracture within the following year is increased by a factor of 3-5. In addition, the presence of a vertebral fracture is associated with an increased risk of hip fracture. In light of these data, treatment of established osteoporosis is extremely important to prevent other fragility fractures. This review examines the therapies approved by the US FDA for the treatment of osteoporosis that have been shown to reduce the incidence of new fractures in patients with established osteoporosis. We evaluated the mechanisms of action, available formulations, efficacy in preventing fractures and increasing bone mineral density (BMD), duration of treatment, adverse effects and contraindications to use of alendronic acid (alendronate), risedronic acid (risedronate), calcitonin, raloxifene and teriparatide. All these drugs are able to prevent new vertebral fractures in patients with established osteoporosis. Only alendronic acid and risedronic acid have also been shown to reduce the risk of fracture at the femoral level, but they are contraindicated in patients with upper gastrointestinal diseases. Calcitonin is a good option in subjects with back pain because of its analgesic effect. Raloxifene is useful when patients have high plasma lipid levels or a family history of breast cancer. Teriparatide is indicated in subjects with very low BMD and multiple vertebral fractures. Patient characteristics should determine selection of therapy but the decision is always difficult and fraught with uncertainty.
Asunto(s)
Calcitonina/uso terapéutico , Difosfonatos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Clorhidrato de Raloxifeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Teriparatido/uso terapéutico , Anciano , Calcitonina/efectos adversos , Difosfonatos/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Clorhidrato de Raloxifeno/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Teriparatido/efectos adversosRESUMEN
UNLABELLED: Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation. INTRODUCTION: Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation. MATERIALS AND METHODS: Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study. RESULTS: After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study. CONCLUSIONS: Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.