RESUMO
Abnormal calcium metabolism in sarcoidosis patients can lead to hypercalcemia, hypercalciuria, and kidney stones. Hypercalcemia in sarcoidosis is usually due to increased activity of 1α-hydroxylase in macrophages of pulmonary granulomata, resulting in low levels of 25-hydroxyvitamin D and high levels of calcitriol. Vitamin D supplementation may be dangerous for some sarcoidosis patients and is recommended only for those with decreased 25-hydroxyvitamin D and reduced or normal calcitriol level. Diagnosis, treatment of osteoporosis, and maintenance of bone health are complex issues for sarcoidosis patients. An approach to diagnosis and treatment of bone fragility is presented.
Assuntos
Desmineralização Patológica Óssea/metabolismo , Cálcio/metabolismo , Suplementos Nutricionais/efeitos adversos , Sarcoidose/metabolismo , Vitamina D/farmacologia , Fatores Etários , Desmineralização Patológica Óssea/etiologia , Desmineralização Patológica Óssea/prevenção & controle , Calcitriol/sangue , Fraturas Ósseas/prevenção & controle , Humanos , Conduta do Tratamento Medicamentoso , Ensaios Clínicos Pragmáticos como Assunto , Fatores de Risco , Sarcoidose/complicações , Sarcoidose/terapia , Fatores Sexuais , Vitamina D/metabolismoRESUMO
BACKGROUND: Vascular calcification progression has been associated with the loss of trabecular bone in chronic kidney disease (CKD) patients. There are few data evaluating the relationship between cortical bone loss and vascular calcification in this population. The aim of this study was to prospectively evaluate the association between changes in cortical bone density and coronary artery calcification (CAC) progression in non-dialyzed CKD patients. METHODS: Changes of cortical and trabecular bone, and changes of calcium score, were analyzed using vertebral tomographic images from a prospective study. Automatic delineation of the cortical bone layer was performed by Image J software, and trabecular bone was determined by selecting a region of interest using Vitrea 2® software. Cortical and trabecular bone density (BD) were expressed in Hounsfield Units (HU), and coronary artery calcium score in Agatston Units (AU). RESULTS: Seventy asymptomatic patients [57.8 ± 10.2 years, 63% males, 20% diabetic, estimated glomerular filtration rate (eGFR) = 37.3 (24.8-51.3) mL/min/1.73m2] were followed for 24 months. The mean cortical and trabecular BD did not change over time. While 49 patients lost either bone, 29 (41%) patients lost cortical [- 4.4%/year (ranging from - 7.15 to - 0.5)] and 39 (56%) lost trabecular bone [- 3.15%/year (- 13.7 to - 0.25)]. There was no association between cortical and trabecular BD changes (p = 0.12). CAC was observed in 33 (46%) patients at baseline, and 30 (91%) of them showed CAC progression. While an inverse correlation between trabecular bone and calcium score changes was observed (p = 0.001), there was no correlation between cortical bone and calcium score changes (p = 0.34). CONCLUSION: CKD patients experience either cortical or trabecular bone loss over time, but these changes do not take place simultaneously in all patients. Cortical, unlike trabecular bone loss, is not associated with vascular calcification progression in these patients.
Assuntos
Desmineralização Patológica Óssea , Osso Esponjoso , Insuficiência Renal Crônica/complicações , Calcificação Vascular/diagnóstico , Doenças Assintomáticas , Desmineralização Patológica Óssea/diagnóstico , Desmineralização Patológica Óssea/etiologia , Densidade Óssea , Brasil/epidemiologia , Osso Esponjoso/irrigação sanguínea , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/metabolismo , Tomografia Computadorizada por Raios X/métodos , Calcificação Vascular/epidemiologiaRESUMO
Bone is now considered as a particular endocrine organ. Its endocrine function is not yet fully understood and has been the subject of several conferences at the European Society of Endocrinology Congress 2018. Bone regulates phosphate metabolism by secreting fibroblast growth factor 23; it also regulates glucose metabolism via osteocalcin and energy metabolism, thanks to lipocalin 2, a new hormone acting on the brain. In addition, the incidence of diabetes continues to grow, and its impact on bone has been demonstrated, with an increased risk of fractures regardless the type of diabetes. The mechanism of bone fragility in this disease is not fully known but it involves a decrease in bone turnover and bone demineralization. Recent findings on the role of bone on glucose and mineral metabolism could open therapeutic perspectives, especially for the treatment of diabetes or obesity.
Assuntos
Osso e Ossos/fisiologia , Metabolismo/fisiologia , Desmineralização Patológica Óssea/etiologia , Remodelação Óssea , Complicações do Diabetes , Diabetes Mellitus/epidemiologia , Glândulas Endócrinas/fisiologia , Metabolismo Energético , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/fisiologia , Fraturas Ósseas/etiologia , Glucose/metabolismo , Humanos , Lipocalina-2/fisiologia , Minerais/metabolismo , Osteocalcina/fisiologia , Fosfatos/metabolismo , Fatores de RiscoAssuntos
Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Gastroenterologia/educação , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hepatopatias/enzimologia , Idoso , Autoanticorpos/análise , Desmineralização Patológica Óssea/etiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Feminino , Ferritinas/análise , Ferritinas/metabolismo , Hemocromatose/diagnóstico , Hemocromatose/metabolismo , Hemocromatose/patologia , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/genética , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Cirrose Hepática Biliar/complicações , Hepatopatias/diagnóstico por imagem , Hepatopatias/imunologia , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto JovemRESUMO
PURPOSE: To examine the prevalence and risk factors for hypercalcemia among non-dialysis chronic kidney disease (CKD) patients with mineral and bone disorder (MBD). METHODS: A retrospective cohort study was conducted in Singapore General Hospital, involving all CKD stage 4 and 5 pre-dialysis patients who were on treatment for MBD in June 2016. Each patient was followed up for 1 year and screened for hypercalcemia episodes. Mild, moderate and severe hypercalcemia were defined as corrected calcium of 2.47-3.00, 3.01-3.50 and ≥ 3.51 mmol/l respectively. Patients who were on dialysis, post-renal transplant, post-parathyroidectomy or had no calcium levels taken during the study period were excluded. Details related to patients' clinical information and hypercalcemia episodes were collected. Multivariate logistic regression analysis was performed to evaluate risk factors for hypercalcemia. RESULTS: Of 557 patients, 75 (13.4%) patients developed hypercalcemia. There were 120 (97.6%) mild and 3 (2.4%) moderate hypercalcemia episodes. The daily elemental calcium intake from phosphate binders and usage of vitamin D analogues did not differ between patients with and without hypercalcemia (p > 0.05). After adjusting for covariates, lower baseline iPTH level [odds ratio (OR) 0.96, 95% CI 0.93-0.99], history of hypercalcemia in past 1 year (OR 11.11, 95% CI 3.36-36.75) and immobility (OR 3.34, 95% CI 1.34-8.40) were associated with increased hypercalcemia risk. CONCLUSION: Hypercalcemia affects a significant proportion of pre-dialysis patients with MBD. More studies should be undertaken to evaluate other risk factors associated with hypercalcemia.
Assuntos
Desmineralização Patológica Óssea , Cálcio , Hipercalcemia , Insuficiência Renal Crônica , Vitamina D , Idoso , Desmineralização Patológica Óssea/sangue , Desmineralização Patológica Óssea/etiologia , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Cálcio/sangue , Cálcio/uso terapêutico , Feminino , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/epidemiologia , Hipercalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Estudos Retrospectivos , Fatores de Risco , Singapura/epidemiologia , Vitamina D/sangue , Vitamina D/uso terapêuticoRESUMO
Guidelines for the assessment, diagnosis and therapy of the alterations that characterize the CKD-MBD are an important support in the clinical practice of the nephrologist. Compared to the KDIGO guidelines published in 2009, the 2017 update made changes on some topics on which there was previously no strong evidence both in terms of diagnosis and therapy. The recommendations include the diagnosis of bone anomalies in CKD-MBD and the treatment of mineral metabolism abnormalities with particular regard to hyperphosphataemia, calcium levels, secondary hyperparathyroidism and anti-resorptive therapies. The Italian Study Group on Mineral Metabolism, in reviewing the 2017 recommendations, aimed to assess the weight of the evidence that led to this update. In fact, on some topics there has not been a substantial difference on the degree of evidence compared to the previous guidelines. The Italian Study Group emphasizes the points that may still reserve critical issues, including interpretation, and invites an evaluation that is articulated and personalized for each patient.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica , Corticosteroides/efeitos adversos , Biópsia , Desmineralização Patológica Óssea/etiologia , Desmineralização Patológica Óssea/fisiopatologia , Desmineralização Patológica Óssea/terapia , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/etiologia , Reabsorção Óssea/prevenção & controle , Osso e Ossos/patologia , Cálcio/análise , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Contraindicações de Medicamentos , Soluções para Diálise/química , Humanos , Hipercalcemia/etiologia , Hipercalcemia/prevenção & controle , Hipercalcemia/terapia , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/fisiopatologia , Hiperfosfatemia/dietoterapia , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Vitamina D/uso terapêuticoRESUMO
Metabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO2 at ≥22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO2 and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.
Assuntos
Acidose/tratamento farmacológico , Acidose/fisiopatologia , Ácidos/efeitos adversos , Álcalis/uso terapêutico , Doenças Assintomáticas , Insuficiência Renal Crônica/fisiopatologia , Acidose/sangue , Acidose/etiologia , Ácidos/metabolismo , Desmineralização Patológica Óssea/etiologia , Dióxido de Carbono/sangue , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Insuficiência Renal Crônica/complicações , Fatores de Risco , Bicarbonato de Sódio/uso terapêuticoRESUMO
We describe the clinical outcome of asfotase alfa therapy in a 16-year-old boy with severe childhood hypophosphatasia (HPP), who began therapy at age 15 years. The patient was diagnosed with HPP at age 2 years when he presented with genu varum and premature loss of primary teeth. He had a history of multiple fractures requiring 16 orthopedic surgeries with rod and pin placement in his lower extremities. He had chronic skeletal pain and used cane to ambulate with great difficulty. His height Z score at age 15 years was - 5. He had severe scoliosis and deformity of both legs. Bone radiograph showed hypomineralization and characteristic "tongues" of radiolucency in the distal radius and ulna. His serum alkaline phosphatase level was stable, with elevated serum pyridoxal 5'-phosphate and urine phosphoethanolamine, consistent with HPP. He was started on asfotase alfa 2 mg/kg given subcutaneously thrice weekly. He had marked clinical improvement in mobility with no report of pain after 3 months of treatment. At 6 month, he walked without cane and participated in outdoor activities with peers. Bone radiograph at 6 months showed striking improvement in previous radiolucent areas. At 9 months, his annualized growth velocity was 9.5 cm/year, while growth velocity of arm span was 12 cm/year. However, at 12 months, he was noted to have worsening scoliosis from 60 degrees before therapy to 110 degrees, with a slight decrease in height, necessitating a spinal fusion surgery. In conclusion, treatment with asfotase alfa significantly improved physical function, pain, overall quality of life, and skeletal radiographic findings in this patient. Close monitoring for progression of scoliosis in adolescents with HPP treated with asfotase alfa is recommended.
Assuntos
Fosfatase Alcalina/uso terapêutico , Terapia de Reposição de Enzimas/métodos , Hipofosfatasia/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Desmineralização Patológica Óssea/diagnóstico por imagem , Desmineralização Patológica Óssea/tratamento farmacológico , Desmineralização Patológica Óssea/etiologia , Humanos , Hipofosfatasia/complicações , Hipofosfatasia/fisiopatologia , Masculino , Qualidade de Vida , Radiografia , Escoliose/etiologiaRESUMO
BACKGROUND: Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. METHODS AND FINDINGS: In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33-46 years) and median T-CD4 count was 199 cells/µl (IQR: 113-319 cells/µl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36-72 months) and the median baseline SI was 101 (IQR: 87-116). In multivariable analysis, factors associated with baseline SI were sex (ß = -10.8 [-18.1,-3.5] for women), age (ß = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (ß = +0.8 [0.1,1.5] per unit of BMI), and study site (ß = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. CONCLUSION: Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.
Assuntos
Terapia Antirretroviral de Alta Atividade , Desmineralização Patológica Óssea/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Osteoporose/tratamento farmacológico , Adulto , Desmineralização Patológica Óssea/etiologia , Desmineralização Patológica Óssea/fisiopatologia , Desmineralização Patológica Óssea/virologia , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Burkina Faso , Camarões , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/fisiopatologia , Osteoporose/virologia , Senegal , Tenofovir/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. RECENT FINDINGS: Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. SUMMARY: Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.
Assuntos
Desmineralização Patológica Óssea , Cálcio/metabolismo , Suplementos Nutricionais/efeitos adversos , Fraturas Ósseas/prevenção & controle , Sarcoidose , Vitamina D , Desmineralização Patológica Óssea/etiologia , Desmineralização Patológica Óssea/metabolismo , Desmineralização Patológica Óssea/prevenção & controle , Calcitriol/sangue , Humanos , Conduta do Tratamento Medicamentoso , Sarcoidose/complicações , Sarcoidose/metabolismo , Sarcoidose/terapia , Vitamina D/metabolismo , Vitamina D/farmacologiaRESUMO
OBJECTIVES: We attempted to assess bone mineralization and the frequency of fractures occurrence in women with a history of treatment of anorexia nervosa (AN) in adolescence. METHODS: 47 women (age 20-36.8 years) were re-examined 6.33-21,2 years after the onset of AN symptoms. Bone mineral density (BMD) of total body, lumbar spine, femoral neck, total hip (DXA) and densitometric Vertebral Fracture Assessment (VFA) were performed on 46 of women and BAP, P1NP, CTX, estradiol, testosterone, cortisol, IGF-1, leptin, DHEA-S on 45 of women entered for the current study. Current BMD results were compared with available baseline results from the time of hospitalization. RESULTS: Currently BMD Z-score <-1 examined at any location occurred in 28 from 46 women (including Z-score <-2 in 5 women). In 11 from 12 women with reduced BMD at the time of hospitalization current total body BMD was within the normal range. Lumbar spine BMD was normalized or improved respectively in 5 and 6 from 15 women. Currently increased levels/activity of bone formation markers: P1NP in 27 (60%) and BAP in 28 women (62.2%) were observed. In 7 women (15.6%) increased values of bone formation markers with increased marker of bone resorption (CTX) occurred. Osteoporotic fractures and fractures in the spine in VFA were not observed during the observation period. CONCLUSIONS: Despite early treatment of adolescent-onset AN and good outcomes of the treatment, decreased BMD was currently present in 60.9% of women. During follow-up normalization or significant improvement in BMD results (total body, lumbar spine) were observed in majority of cases.
Assuntos
Anorexia Nervosa/complicações , Anorexia Nervosa/fisiopatologia , Desmineralização Patológica Óssea/etiologia , Densidade Óssea/fisiologia , Vértebras Lombares/lesões , Fraturas por Osteoporose/etiologia , Absorciometria de Fóton , Adulto , Desmineralização Patológica Óssea/diagnóstico por imagem , Densitometria , Difosfonatos/uso terapêutico , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagemRESUMO
BACKGROUND: Starvation in early life can lead to premature metabolic syndrome and bone demineralization. Osteoporosis in the Jewish population may not yet be a recognized syndrome, but the harsh conditions to which Holocaust survivors were exposed may have increased the incidence of the condition. Immigrants and refugees who came to Israel from East Africa and Yemen - whether decades ago or more recently - may have been at increased risk of under-nutrition during pregnancy, affecting both the mother and consequently the offspring. This malnutrition may be further exacerbated by rapid overfeeding in the adopted developed country. This problem was also recognized at the turn of the 21st century in poor and underdeveloped countries and is becoming a global public health issue. In this review, the risks for premature metabolic syndrome and bone demineralization are enumerated and preventive measures outlined.
Assuntos
Desmineralização Patológica Óssea , Transtornos da Nutrição Infantil , Síndrome Metabólica , Osteoporose , Saúde Pública , Inanição/complicações , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Desmineralização Patológica Óssea/etiologia , Desmineralização Patológica Óssea/fisiopatologia , Criança , Transtornos da Nutrição Infantil/complicações , Transtornos da Nutrição Infantil/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Holocausto/estatística & dados numéricos , Humanos , Israel/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/fisiopatologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Saúde Pública/legislação & jurisprudência , Saúde Pública/métodos , Medição de Risco , Fatores de Risco , Inanição/fisiopatologiaRESUMO
Low bone mineral density (BMD) is a common problem in adults with cystic fibrosis (CF), the etiology of which is multifactorial. In this study, we provide the first evidence that ivacaftor improves BMD in CF patients carrying the p.Gly551Asp mutation. Consistently, in vitro experiments with TNF-α-stimulated primary F508del-CFTR osteoblasts demonstrated that correction of p.Phe508del-CFTR markedly decreased RANKL protein production, a major factor of bone resorption. These clinical and fundamental observations suggest that rescue of mutated CFTR protein improves bone remodeling and support the link between CFTR and bone cell physiology. These findings represent a step forward in the development of potential new therapies for CF-related bone disease.
Assuntos
Aminofenóis/administração & dosagem , Desmineralização Patológica Óssea , Densidade Óssea/efeitos dos fármacos , Fibrose Cística , Quinolonas/administração & dosagem , Adulto , Desmineralização Patológica Óssea/etiologia , Desmineralização Patológica Óssea/metabolismo , Desmineralização Patológica Óssea/terapia , Densidade Óssea/fisiologia , Células Cultivadas , Agonistas dos Canais de Cloreto/administração & dosagem , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Estatística como AssuntoRESUMO
Radiation therapy is commonly used to treat cancer patients but exhibits adverse effects, including insufficiency fractures and bone loss. Epigenetic regulation plays an important role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, we reported local bone changes after single-dose exposure to (137)CS irradiation in rats. Femur bone mineral density (BMD) and trabecular bone volume in the tibia were significantly decreased at 12 weeks after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also significantly reduced at 12 weeks after irradiation exposure. ALP-positive OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by 50.8% at 12 weeks after exposure. In contrast to the decreased expression of Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks after single-dose (137)CS irradiation in BMSCs. Together, our results demonstrated that single-dose (137)CS irradiation induces BMD loss and the deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2 expression increased and osteoblastogenesis decreased after irradiation. The underlying mechanisms warrant further investigation.
Assuntos
Desmineralização Patológica Óssea/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Osteoblastos/metabolismo , Animais , Fenômenos Biomecânicos , Desmineralização Patológica Óssea/etiologia , Densidade Óssea , Células da Medula Óssea/citologia , Diferenciação Celular , Ensaio de Imunoadsorção Enzimática , Epigênese Genética , Fêmur/diagnóstico por imagem , Fêmur/efeitos da radiação , Masculino , Neoplasias/metabolismo , Osteogênese , Ratos , Tíbia/diagnóstico por imagem , Tíbia/efeitos da radiação , Microtomografia por Raio-XRESUMO
Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.
Assuntos
Cálcio da Dieta/farmacologia , Suplementos Nutricionais/efeitos adversos , Cálculos Renais/etiologia , Vitamina D/farmacologia , Animais , Apatitas/metabolismo , Desmineralização Patológica Óssea/etiologia , Cálcio da Dieta/sangue , Cálcio da Dieta/urina , Modelos Animais de Doenças , Sinergismo Farmacológico , Cálculos Renais/sangue , Cálculos Renais/química , Cálculos Renais/urina , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/metabolismo , Eliminação Renal , Espectroscopia de Infravermelho com Transformada de Fourier , Microtomografia por Raio-XRESUMO
Anorexia nervosa (AN) most often has its onset in adolescence, which is a crucial period to achieve peak bone mass. The hormonal abnormalities (hypoestrogenism, hypercortisolism, decreased secretion of dehydroepiandrosterone, testosterone, insulin-like growth factor) and malnutrition are associated with profound bone mineralization disorders. Densitomertic bone mineral density (BMD) values for osteopenia and osteoporosis were found respectively in 35-98% and 13-50% of women with AN. Prospective studies indicate a further decline in BMD at the beginning of treatment and a crucial importance of weight gain and return of spontaneous menses for its growth. Due to frequent chronic and relapsing course of AN densitometric assessment of BMD is recommended in all patients with AN and amenorrhea lasting around twelve months. In order to establish standards for the treatment of osteoporosis in AN, studies on pharmacological treatment are conducted. There are promising results indicating the improvement in BMD after treatment with physiologic oestrogen replacement treatment and sequential administration of medroxyprogesterone in teenage girls and bisphosphonates in adult women. Supplementation of vitamin D and adequate consumption of calcium from diet are recommended. Further studies on the effectiveness of long-term treatment of osteoporosis with regard to the possibility of increase in BMD and reducing the risk of osteoporotic fractures are needed.
Assuntos
Anorexia Nervosa/complicações , Desmineralização Patológica Óssea/tratamento farmacológico , Desmineralização Patológica Óssea/etiologia , Fraturas Ósseas/prevenção & controle , Adolescente , Adulto , Distribuição por Idade , Desmineralização Patológica Óssea/epidemiologia , Cálcio da Dieta/uso terapêutico , Difosfonatos/uso terapêutico , Estradiol/uso terapêutico , Feminino , Humanos , Masculino , Osteoporose/etiologia , Osteoporose/prevenção & controle , Aumento de Peso , Adulto JovemRESUMO
PURPOSE: To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. MATERIALS AND METHODS: Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Δ%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Δ%HU was compared against radiation dose using Pearson's linear correlation. RESULTS: Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Δ%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R=-0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (ß=0.830) on determining post-RT HU, while number of months post RT (ß=-0.213) and radiation point dose (ß=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our model's predicted HU were within ±20 HU of the actual value in 53% of cases, 70% of the predictions were within ±30 HU, 81% were within ±40 HU, and 90% were within ±50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. CONCLUSIONS: Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT.
Assuntos
Desmineralização Patológica Óssea/etiologia , Densidade Óssea/efeitos da radiação , Neoplasias do Sistema Digestório/radioterapia , Vértebras Lombares/efeitos da radiação , Lesões por Radiação/etiologia , Vértebras Torácicas/efeitos da radiação , Adulto , Idoso , Antineoplásicos/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Fraturas por Compressão/etiologia , Fraturas Espontâneas/etiologia , Humanos , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia , Vértebras Torácicas/lesões , Tomografia Computadorizada por Raios X/métodosRESUMO
Mucolipidoses II and III (ML II and ML III) are lysosomal disorders in which the mannose 6-phosphate recognition marker is absent from lysosomal hydrolases and other glycoproteins due to mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Both disorders are caused by the same gene, but ML II represents the more severe phenotype. Bone manifestations of ML II include hip dysplasia, scoliosis, rickets and osteogenesis imperfecta. In this study, we sought to determine whether a recombinant adeno-associated viral vector (AAV2/8-GNPTAB) could confer high and prolonged gene expression of GNPTAB and thereby influence the pathology in the cartilage and bone tissue of a GNPTAB knock out (KO) mouse model. The results demonstrated significant increases in bone mineral density and content in AAV2/8-GNPTAB-treated as compared to non-treated KO mice. We also showed that IL-6 (interleukin-6) expression in articular cartilage was reduced in AAV2/8-GNPTAB treated ML II mice. Together, these data suggest that AAV-mediated expression of GNPTAB in ML II mice can attenuate bone loss via inhibition of IL-6 production. This study emphasizes the value of the MLII KO mouse to recapitulate the clinical manifestations of the disease and highlights its amenability to therapy.
Assuntos
Desmineralização Patológica Óssea/etiologia , Dependovirus/genética , Expressão Gênica , Vetores Genéticos/genética , Mucolipidoses/genética , Mucolipidoses/patologia , Transdução Genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Animais , Desmineralização Patológica Óssea/diagnóstico , Desmineralização Patológica Óssea/terapia , Densidade Óssea , Modelos Animais de Doenças , Ordem dos Genes , Marcação de Genes , Loci Gênicos , Terapia Genética , Vetores Genéticos/administração & dosagem , Genótipo , Humanos , Camundongos , Camundongos Knockout , Mucolipidoses/terapia , FenótipoRESUMO
Mucolipidosis type II (ML II, OMIM 252,500) is an autosomal recessive disorder clinically characterized by facial dysmorphia similar to Hurler syndrome and pronounced gingival hypertrophy. The disorder is caused by a defect in targeting acid hydrolases on the surface of lysosomes, which impede their entry and lead to accumulation of undigested substrates in lysosomes. The onset of the symptoms is usually in infancy, beginning in the 6th month of life. Early onset, at birth or even in utero, is a sign of severity and involves the specific dysmorphia as well as skeletal dysplasia related to hyperparathyroidism. We report on a severe neonatal form of this disorder revealed by respiratory distress with severe chest deformity. The dysmorphic syndrome, combining coarse features, pronounced gingival hypertrophy, with diffuse bone demineralization and secondary hyperparathyroidism associating significant elevation of parathyroid hormone and alkaline phosphatase with normal levels of vitamin D and calcium were characteristics of mucolipidosis type II. Recognizing this specific association of anomalies helps eliminate the differential diagnosis and establish appropriate diagnosis and care.
Assuntos
Mucolipidoses/diagnóstico , Fosfatase Alcalina/sangue , Desmineralização Patológica Óssea/etiologia , Hipertrofia Gengival/etiologia , Humanos , Hiperparatireoidismo Secundário/etiologia , Recém-Nascido , Masculino , Hormônio Paratireóideo/sangue , Índice de Gravidade de DoençaRESUMO
PURPOSE: The purpose of this paper was to review the literature concerning the treatment of chronic kidney disease-mineral bone disorder (CKD-MBD) in the elderly peritoneal dialysis (PD) patient. RESULTS: Chronic kidney disease-mineral bone disorder is a major problem in the elderly PD patient, with its associated increased fracture risk, vascular calcification, and accelerated mortality fracture risk. Peritoneal dialysis, however, bears a lower risk than hemodialysis (HD). The approach to CKD-MBD prophylaxis and treatment in the elderly PD patient is similar to other CKD patients, with some important differences. Avoidance of hypercalcemia, hyperphosphatemia, and hyperparathyroidism is important, as in other CKD groups, and is generally easier to attain. Calcium-free phosphate binders are recommended for normocalcemic and hypercalcemic patients. Normalization of vitamin D levels to > 75 nmol/L (> 30 pg/L) and low-dose active vitamin D therapy is recommended for all patients. Hyperparathryoidism is to be avoided by using active vitamin D and cinacalcet. Particular attention should be paid to treating protein malnutrition. Fracture prophylaxis (exercise, use of walkers, dwelling modifications) are important. Hypomagnesemia is common in PD and can be treated with magnesium supplements. Vitamin K deficiency is also common and has been identified as a cause of vascular calcification. Accordingly, warfarin treatment for this age group is problematic. CONCLUSION: While treatment principles are similar to other dialysis patient groups, physicians should be aware of the special problems of the elderly group.