RESUMEN
The evolution of pain and quality of life after a symptomatic vertebral fracture differs according to patient gender, with a worse evolution in women independently of the treatment received. PURPOSE: In a previous randomized clinical study comparing the effect of vertebroplasty (VP) vs. conservative therapy (CT) on pain evolution and quality of life (QoL) of patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain in 23% of subjects, independently of the therapy received. This study analyses the effect of gender on the evolution of pain and QoL in these subjects. METHODS: 118/125 randomized patients (27 males/91 females) with recent symptomatic VFs were evaluated. All received a standardized analgesic and antiosteoporotic format of treatment. Pain and QoL were evaluated by VAS and Qualeffo-41, respectively, at baseline, at 2 weeks and 2 and 6 months. We compared pain evolution and QoL after treatment (CT vs. VP) according to gender, and analysed factors including age, time of evolution, treatment received, baseline VAS, previous VFs (total and recent), incidental VFs, lumbar and femoral T-scores, and analgesic and antiosteoporotic treatment. RESULTS: At baseline, there were no differences in age (males 74.8 ± 11.2 vs. females:73.2 ± 8.7 years), time of evolution, number of VFs (males:3.8 ± 2.4 vs. females: 3.1 ± 2.4), treatment received (VP, males:59%, females:45%), lumbar or femoral T-score, baseline VAS (males:6.8 ± 2.1 vs. females:6.8 ± 2.2) or Qualeffo score (males:52.2 ± 24.4 vs. females:59.7 ± 20.6). Pain and QoL evolution differed according to gender, being better in males. These differences were significant after two months independently of the treatment and the development of incidental VF during follow-up. CONCLUSIONS: Pain and QoL evolution after a symptomatic VF differs according to gender, with a worse evolution in women independently of the treatment received.
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Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Masculino , Humanos , Femenino , Calidad de Vida , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Dolor de Espalda , Analgésicos/uso terapéutico , Fracturas Osteoporóticas/cirugíaRESUMEN
Nearly 10% of subjects with severe idiopathic osteoporosis present pathogenic WNT1 mutations. Clinical characteristics include a family history of osteoporosis, early adulthood onset, and fragility fractures which may evolve to pseudoarthrosis. WNT1 should be genetically screened in these patients as the phenotype is often variable and therapeutic approaches may differ. INTRODUCTION: Recent studies have shown that homozygous WNT1 gene mutations may be related to severe osteoporosis resembling osteogenesis imperfecta (OI). Conversely, heterozygous WNT1 mutations are linked to a milder phenotype of early-onset osteoporosis. Treatment with bisphosphonates is reported to be unsatisfactory. Our aim was to analyze the presence and prevalence of WNT1 mutations and the main associated clinical characteristics in subjects with primary early-onset osteoporosis. METHODS: A cohort comprising 56 subjects (aged 19-60 years) with severe, early-onset osteoporosis was screened by massive parallel sequencing with a 23-gene panel. The gene panel included 19 genes known to cause OI (including the WNT1 gene), three genes related to osteoporosis, and the gene related to hypophosphatasia (ALPL). RESULTS: We identified five patients (3 men) with heterozygous WNT1 variants. All presented severe osteoporosis with early fracture onset and a family history of fragility fractures. None presented a characteristic phenotype of OI or skeletal deformities. One patient was previously treated with bisphosphonates, presenting inadequate response to treatment and two developed pseudoarthrosis after upper arm fractures. All subjects were diagnosed in adulthood. CONCLUSIONS: Nearly 1/10 adult subjects with severe idiopathic osteoporosis may present pathogenic WNT1 mutations. Clinical characteristics commonly include a family history of osteoporosis, onset in early adulthood, marked decrease in bone mass, and prevalent fractures, particularly vertebral. WNT1 should be genetically screened in these subjects as the phenotype is often variable and the therapeutic approach may differ. The role of WNT1 mutations in the development of pseudoarthrosis should also be elucidated.
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Osteoporosis , Proteína Wnt1 , Humanos , Difosfonatos/uso terapéutico , Fracturas del Húmero , Mutación , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/diagnóstico , Osteoporosis/genética , Osteoporosis/tratamiento farmacológico , Seudoartrosis/tratamiento farmacológico , Proteína Wnt1/genéticaRESUMEN
OBJECTIVE: To analyse the clinical utility of trabecular bone score (TBS) evaluation for fracture risk assessment in glucocorticoid (GC)-treated patients compared with BMD assessment. METHODS: One hundred and twenty-seven patients on GC treatment were included [mean age 62 (18) years, 63% women] in this cross-sectional study. The medical history, anthropometric data, lumbar and femoral BMD (DXA) [considering osteoporosis (OP): T-score ⩽-2.5], TBS (considering degraded microarchitecture: <1.230) and dorsolumbar X-ray [to assess vertebral fractures (VF)] were evaluated. BMD and TBS sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were evaluated to determine the diagnostic accuracy of the two methods. RESULTS: All patients were receiving GC treatment for autoimmune diseases during 47.7 (68.9) months at a mean daily dose of 14.5 mg; 17% had VF, 28% any type of fragility fracture (VF + non-VF), 29% OP and 52% degraded microarchitecture. Degraded microarchitecture was significantly more frequent than densitometric OP in patients with VF (76% vs 38%) and with any fragility fracture (69% vs 36%). For VF, TBS and BMD sensitivity, specificity, PPV, and NPV were 0.76, 0.53, 0.25 and 0.92, and 0.38, 0.72, 0.22 and 0.85, respectively. Specificity increased to 0.89 for VF and 0.9 for any fragility fracture on combining BMD+TBS. TBS had better ability than BMD to discriminate between patients with fracture, especially VF (area under the curve = 0.73). CONCLUSION: TBS seems to have greater discriminative power than BMD for fracture risk assessment in GC-treated patients, confirming the utility of this method as a complementary tool in the diagnosis of GC-induced OP.
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Densidad Ósea , Hueso Esponjoso/diagnóstico por imagen , Fémur/diagnóstico por imagen , Glucocorticoides/efectos adversos , Vértebras Lumbares/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Fracturas de la Columna Vertebral/epidemiología , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Osteoporosis/complicaciones , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Medición de Riesgo , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiologíaRESUMEN
BACKGROUND AND AIMS: Osteoporosis is a common complication in patients with primary biliary cholangitis. Both bilirubin and lithocholic acid (LCA) result in detrimental effects on osteoblastic cells, and ursodeoxycholic acid (UDCA) counteracts these outcomes. However, there is no information on the consequences of these retained substances of cholestasis and sera from cholestatic patients in osteocytes. METHODS: The impact of bilirubin, LCA, UDCA and serum from jaundiced patients on viability, differentiation, mineralization and apoptosis has been assessed in MLO-Y4 and MLO-A5 osteocyte cell lines. Effects on gene expression were assessed in these cells and in human bone fragments. RESULTS: Lithocholic acid 10 µmol/L and bilirubin 50 µmol/L decreased viability in MLO-Y4 and MLO-A5 cells (11% and 53% respectively; P ≤ .01). UDCA alone or combined with LCA or bilirubin increased cell viability. Jaundiced sera decreased cell viability (56%), an effect which was reverted by UDCA. Bilirubin decreased differentiation by 47% in MLO-Y4 (P ≤ .01) and mineralization (87%) after 21 days in MLO-A5 (P ≤ .03). Both bilirubin and LCA increased apoptosis in MLO-Y4, and UDCA diminished the apoptotic effect. Moreover, bilirubin down-regulated RUNX2 and up-regulated RANKL gene expression in bone tissue, MLO-Y4 and MLO-A5 cells, and LCA up-regulated RANKL expression in bone tissue. UDCA 100 µmol/L increased the gene expression of all these genes in bone tissue and MLO-Y4 cells and neutralized the decreased RUNX2 expression induced by bilirubin. CONCLUSION: Bilirubin and LCA have damaging consequences in osteocytes by decreasing viability, differentiation and mineralization, increasing apoptosis and modifying gene expression, effects that are neutralized by UDCA.
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Colestasis , Osteoporosis , Ácidos y Sales Biliares , Bilirrubina , Huesos , Humanos , OsteocitosAsunto(s)
Fracturas Óseas , Fracturas por Estrés , Osteoporosis , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/etiología , Humanos , Osteoporosis/complicaciones , Osteoporosis/diagnóstico , Esternón/diagnóstico por imagenRESUMEN
Hematopoietic stem cell (HSC) self-renewal is regulated by osteoblast and/or endothelial cells within the hematopoietic niche. However, the true identity of the supporting cells and the nature of the secreted factors remain uncertain. We developed a novel mouse model and analyzed whether circulating human peripheral hematopoietic lineage negative/AP+ (lin-/AP+) cells support hematopoiesis in vivo. Thus, immunocompromised (Rag) mice expressing thymidine kinase (Tk) under the control of the 3.6Col1α1 promoter (Tk-Rag) were treated with ganciclovir, resulting in osteoblast progenitor cell ablation and subsequent loss of hematopoiesis (evaluated by measuring mouse Ter119+ erythroid cells). Following hematopoietic cell depletion, human bone marrow-derived marrow stromal cells (MSCs) or lin-/AP+ cells were infused into Tk-Rag mice and compared with saline infusions. Ganciclovir significantly reduced (7.4-fold) Ter119+ cells in the bone marrow of Tk-Rag mice compared to saline injections. Infusion of either MSCs or lin-/AP+ cells into ganciclovir-treated mice resulted in a 3.3-fold and 2.7-fold increase (P < 0.01), respectively, in Ter119+ cells compared to mice receiving saline. Relative to lin-/AP- cells, lin-/AP+ cells expressed high levels of mesenchymal, endothelial, and hematopoiesis supporting genes. Thus, human peripheral blood lin-/AP+ cells represent a novel cell type capable of supporting hematopoiesis in a manner comparable to MSCs.
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Hematopoyesis/fisiología , Células Madre Hematopoyéticas/citología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/fisiología , Linaje de la Célula , Femenino , Citometría de Flujo , Ganciclovir/farmacología , Hematopoyesis/efectos de los fármacos , Hematopoyesis/genética , Células Madre Hematopoyéticas/metabolismo , Humanos , RatonesRESUMEN
In a recent randomized controlled trial comparing vertebroplasty (VP) versus conservative treatment (CT) in patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain (CBP) in nearly one-quarter of patients. The aim of this study was to identify the risk factors related to the development of severe CBP in these subjects. We evaluated risk factors including visual analog scale (VAS) at baseline and during the 1-year follow-up, age, gender, symptom onset time, number, type and severity of VF at baseline, number of vertebral bodies treated, incident VF, and antiosteoporotic treatment, among others. CBP was considered in patients with VAS ≥ 7 at 12 months. 91/125 patients completed the 12-months follow-up. CBP was observed in 23% of VP-treated patients versus 23% receiving CT. Patients developing CBP after VP showed a longer symptom onset time (82% ≥ 4 months in VP vs. 40% in CT, P = 0.03). On univariate analysis, female gender (OR 1.52; 95% CI 1.47-1.57, P < 0.0001), multiple acute VF (OR 1.79; 95% CI 1.71-1.87, P < 0.0001), VAS ≥ 7 two months after treatment (OR 11.04; 95% CI 6.71-18.17, P < 0.0001), and type of antiosteoporotic drug (teriparatide) (OR 0.12; 95% CI 0.03-0.60, P = 0.0236) were risk factors of CBP development in both groups. In the multivariate analysis, the main risk factors were baseline and post-treatment VAS ≥ 7, longer symptom onset time, and type of antiosteoporotic treatment. In conclusion, 23% of patients with symptomatic osteoporotic VF developed severe CBP independently of the type of treatment. Symptom onset time before VP and persistence of severe CBP after treatment were the main factors related to CBP with teriparatide treatment decreasing the risk of this complication.
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Dolor de Espalda/etiología , Dolor Crónico/etiología , Vértebras Lumbares/cirugía , Fracturas Osteoporóticas/complicaciones , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Vertebroplastia/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Factores de Riesgo , Fracturas de la Columna Vertebral/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: The prevalence of carbohydrate metabolism disorders in patients who receive total parenteral nutrition (TPN) is not well known. These disorders can affect the treatment, metabolic control, and prognosis of affected patients. The aims of this study were to determine the prevalence in noncritically ill patients on TPN of diabetes, prediabetes, and stress hyperglycemia; the factors affecting hyperglycemia during TPN; and the insulin therapy provided and the metabolic control achieved. METHODS: We undertook a prospective multicenter study involving 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included, and data were collected on demographic, clinical, and laboratory variables (glycated hemoglobin, C-reactive protein [CRP], capillary blood glucose) as well as insulin treatment. RESULTS: The study included 605 patients. Before initiation of TPN, the prevalence of known diabetes was 17.4%, unknown diabetes 4.3%, stress hyperglycemia 7.1%, and prediabetes 27.8%. During TPN therapy, 50.9% of patients had at least one capillary blood glucose of >180 mg/dL. Predisposing factors were age, levels of CRP and glycated hemoglobin, the presence of diabetes, infectious complications, the number of grams of carbohydrates infused, and the administration of glucose-elevating drugs. Most (71.6%) patients were treated with insulin. The mean capillary blood glucose levels during TPN were: known diabetes (178.6 ± 46.5 mg/dL), unknown diabetes (173.9 ± 51.9), prediabetes (136.0 ± 25.4), stress hyperglycemia (146.0 ± 29.3), and normal (123.2 ± 19.9) (P<.001). CONCLUSION: The prevalence of carbohydrate metabolism disorders is very high in noncritically ill patients on TPN. These disorders affect insulin treatment and the degree of metabolic control achieved.
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Diabetes Mellitus/epidemiología , Hiperglucemia/epidemiología , Insulina/uso terapéutico , Nutrición Parenteral Total/efectos adversos , Estado Prediabético/epidemiología , Adulto , Anciano , Glucemia/análisis , Diabetes Mellitus/metabolismo , Femenino , Humanos , Hiperglucemia/metabolismo , Masculino , Persona de Mediana Edad , Estado Prediabético/metabolismo , Prevalencia , Estudios ProspectivosRESUMEN
UNLABELLED: Osteoporosis resulting in bone fractures is a complication in patients with primary biliary cirrhosis (PBC). Once-weekly alendronate improves bone mass and is well tolerated in these patients, but there is a concern because of poor compliance. Therefore, the efficacy, adherence, and safety of monthly ibandronate (150 mg) with weekly alendronate (70 mg) were compared in a randomized, 2-year study in 42 postmenopausal women with PBC and osteoporosis. Bone mineral density (BMD) of the lumbar spine and proximal femur (by DXA), liver function, and bone markers were measured at entry and every 6 months over 2 years. Adherence to therapy was assessed by the Morisky-Green score. At enrollment, the two groups were similar with respect to age, BMD, severity of cholestasis, previous fractures, and bone markers. Thirty-three patients, 14 in the ibandronate group and 19 in the alendronate group, completed the trial. At 2 years both treatments resulted in a significant increase in BMD at the lumbar spine (from 0.875 ± 0.025 to 0.913 ± 0.026 g/cm(2), P < 0.001 with alendronate, and from 0.898 ± 0.024 to 0.949 ± 0.027 g/cm(2), P < 0.001 with ibandronate). The mean percentage change was 4.5% and 5.7%, respectively (P = not significant). BMD increased at the total hip by 2.0% and 1.2%, respectively. Changes in bone markers were similar in both groups and one patient with alendronate developed a new vertebral fracture. Adherence to therapy was higher with ibandronate (P = 0.009). Neither treatment impaired liver function or cholestasis. CONCLUSION: Both regimens, weekly alendronate and monthly ibandronate, improve bone mass and are comparable in safety for osteoporosis therapy in patients with PBC, although adherence is higher with the monthly regimen. Further larger studies are needed to assess fracture prevention.
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Fracturas Óseas/prevención & control , Cirrosis Hepática Biliar/tratamiento farmacológico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Administración Oral , Anciano , Alendronato/administración & dosificación , Densidad Ósea , Difosfonatos , Esquema de Medicación , Femenino , Humanos , Ácido Ibandrónico , Cirrosis Hepática Biliar/complicaciones , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Cooperación del Paciente , Resultado del TratamientoRESUMEN
BACKGROUND: Low bone turnover osteoporosis is common in cholestatic diseases. Ursodeoxycholic acid (UDCA) counteracts the damaging effects of bilirubin or lithocholic acid (LCA) on osteoblast viability, proliferation and mineralisation. UDCA is anti-apoptotic in various cell lines, but this effect in bone cells is unknown. Therefore, the consequences of bilirubin and LCA on apoptosis, and whether UDCA has anti-apoptotic effects have been assessed on osteoblasts. MATERIALS AND METHODS: Human osteoblasts (hOB) and osteosarcoma cell line (Saos-2) were treated with camptothecin as a pro-apoptotic agent, and UDCA, LCA and bilirubin. Apoptosis was determined by DNA fragmentation, flow cytometry, caspase-3 activity and expression of pro-apoptotic (Bcl-2-associated X protein BAX) and anti-apoptotic (BCL2 and BCL2-like 1 protein, BCL2L) genes. RESULTS: Both LCA (10 µM) and bilirubin (50 µM) induced apoptosis as indicated by DNA fragmentation (4·7- and 3·7-fold, respectively, P < 0·001), caspase-3 activity and flow cytometry in Saos-2 and hOB. UDCA (10 µM) reduced the apoptotic effects of camptothecin (0·5 µM) by 61%, (P < 0·001) and counteracted the apoptotic effects of LCA and bilirubin determined by DNA fragmentation (56% and 60%, respectively, P < 0·001), cytometry and caspase-3 activity in Saos-2, with lower effects in hOB. UDCA (10 µM) downregulated BAX (75%), upregulated BCL2L (10-fold, P < 0·01) genes, and neutralised BAX upregulation (P < 0·01) and BCL2L downregulation (P < 0·01) induced by LCA and bilirubin. CONCLUSIONS: Bilirubin and LCA induce apoptosis in osteoblastic cells. UDCA counteracts the apoptotic consequences of these two substances, and therefore, it may have further beneficial effects on the decreased bone formation in the cholestasis.
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Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Bilirrubina/farmacología , Colagogos y Coleréticos/farmacología , Osteoblastos/efectos de los fármacos , Ácido Ursodesoxicólico/farmacología , Antineoplásicos Fitogénicos/farmacología , Camptotecina/farmacología , Línea Celular Tumoral , Detergentes/farmacología , Humanos , Ácido Litocólico/farmacología , Regulación hacia Arriba , Proteína X Asociada a bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/genéticaRESUMEN
Bone formation is suppressed in glucocorticoid-induced osteoporosis. One of the mechanisms by which glucocorticoids depress bone formation is through their effects on the Wnt/ß-catenin signaling pathway, a critical regulator of osteoblastogenesis. Thus, Wnt signaling induces the differentiation of osteoblast precursors toward mature osteoblasts and prevents osteoblast and osteocyte apoptosis. Glucocorticoids increase the expression of Wnt signaling antagonists (sclerostin and Dkk-1) in experimental studies in rodents and cell cultures. However, the scarce data of their effects in humans are somewhat contradictory, probably due to the dose and duration of treatment as well as the characteristics of the patients. A progressive decrease in Dkk-1 serum levels and an increase in circulating sclerostin levels at long-term follow-up have recently been reported in patients treated with high doses of glucocorticoids. This review describes the most recent data on the effects of glucocorticoids on the Wnt signaling pathway, especially on their antagonists, sclerostin and Dkk-1.
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Proteínas Morfogenéticas Óseas/fisiología , Marcadores Genéticos/fisiología , Glucocorticoides/efectos adversos , Osteoporosis/inducido químicamente , Vía de Señalización Wnt/fisiología , Proteínas Adaptadoras Transductoras de Señales , Densidad Ósea/fisiología , Humanos , Péptidos y Proteínas de Señalización Intercelular/fisiología , Osteoporosis/fisiopatología , Fracturas Osteoporóticas/fisiopatología , Transducción de SeñalRESUMEN
OBJECTIVE: To analyse the incidence and factors related to the development and clinical evolution of fractures in patients with traumatic spinal cord injury. DESIGN: A retrospective 10-year follow-up study. SETTING: Neurorehabilitation centre. SUBJECTS: Sixty-three patients (50M/13F) with a mean age of 36 ± 20 years with recent traumatic spinal cord injury attended over a one-year period (January to December 2000). MAIN MEASURES: Medical reports were reviewed, evaluating risk factors for osteoporosis, fracture incidence during the 10 years following spinal cord injury, severity (ASIA score) and level of spinal cord injury (paraplegia/tetraplegia), type of lesion (spastic/flaccid), weight-bearing standing activity, and the cause, location and evolution of the fracture. RESULTS: Of the 129 patients attending during the study period, 75 had traumatic spinal cord injury (7 died and 5 had no follow-up). Finally, 63 patients were included. Fifty-four per cent had complete motor injury (ASIA A). Twenty-five per cent of these patients developed fractures, with 2.9 fractures per 100 patient-years. The femur was the most frequent location of the fractures. Fractures were observed 6.4 ± 2.4 years after spinal cord injury (range 2-10 years), all in males. Most fractures (70%) were related to low-impact injuries. Fifty per cent presented with associated clinical complications and only 20% of the patients had received anti-osteoporotic treatment. Spinal cord injury severity was the only risk factor for the development of fractures (complete spinal cord injury (ASIA A)) (RR 4.043; 95% confidence interval (CI) 1.081-23.846, P = 0.037). CONCLUSION: The incidence of fractures after spinal cord injury is high, with severity and time since spinal cord injury being the main determinants for their development. Fractures were frequently associated with clinical complications. However, the use of anti-osteoporotic treatment was uncommon.
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Fracturas Óseas/etiología , Osteoporosis/etiología , Paraplejía/etiología , Traumatismos de la Médula Espinal/complicaciones , Adulto , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Comorbilidad , Femenino , Fracturas Óseas/epidemiología , Fracturas Óseas/prevención & control , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológico , Paraplejía/complicaciones , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Factores de Tiempo , Índices de Gravedad del Trauma , Adulto JovenRESUMEN
Vertebral fractures (VFs) are the most common osteoporotic fractures in the general population, and they have been associated with high mortality, decreased quality of life, and high risk of subsequent fractures, especially when recent, multiple, or severe. Currently, VF diagnosis and classification determine fracture risk and the most appropriate anti-osteoporotic treatment. However, VFs are clearly underdiagnosed, especially in patients with chronic kidney disease (CKD), and CKD-associated osteoporosis has been disregarded until recently. VFs are associated with higher morbidity and mortality, and their prevalence and incidence differ depending on the grade of renal dysfunction (CKD G1-G5) and/or the type of renal replacement therapy (dialysis or transplantation). In addition to classical risk factors [such as higher age, female sex, reduced bone mineral density, diabetes and steroid use], various other factors have been associated with an increased risk of VFs in CKD, including CKD grade, haemodialysis vintage, time since renal transplantation, low or high intact parathyroid hormone and phosphate levels, and/or vitamin D and K1 deficiencies. Importantly, several clinical societies have recently modified their algorithms according to the fracture risk classification (including the presence of VFs) and determined the most appropriate anti-osteoporotic treatment for the general population. However, there are no specific guidelines addressing this topic in patients with CKD despite an important paradigm shift regarding the prognostic value of bone mineral density in 2017 after the publication of the CKD-Mineral and Bone Disorder Kidney Disease: Improving Global Outcomes guidelines. A proactive attitude towards diagnosis, treatment, and research is proposed to avoid therapeutic nihilism.
RESUMEN
In recent years, there has been speculation about the possibility of a reduction in the incidence of fractures after liver transplantation (LT) because of changes in the characteristics of candidates and the use of different immunosuppressive therapies. We analyzed the characteristics of LT candidates (CTC) and compared them with historical data from a group of LT candidate patients (HTC). Data from 60 CTC patients consecutively included in a screening program of metabolic bone disease were compared with data from 60 HTC patients prospectively evaluated between 1992 and 1993. In all patients, we analyzed the clinical and laboratory characteristics, bone mineral density (BMD) dual-energy X-ray absorptiometry, and skeletal fractures. Patients in the CTC group were older than patients in the HTC group. The CTC group had lower femoral neck T scores. No differences were observed between groups in the proportion of patients with osteoporosis (22 vs. 30 %, p = ns) or fractures (36 vs. 33 %, p = ns). The percentage of patients with normal BMD decreased from 38 to 20 %. 25(OH)D values were low in both groups. Only 7.5 % of the CTC patients received calcium and/or vitamin D supplementation. The prevalence of fractures among CTC patients was similar to that seen two decades ago. At present, candidates for LT are older and have lower femoral bone mass. Vitamin D deficiency remains frequent; however, calcium and/or vitamin D supplementation is uncommon.
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Enfermedades Óseas/complicaciones , Fallo Hepático/complicaciones , Trasplante de Hígado/efectos adversos , Absorciometría de Fotón , Adulto , Anciano , Densidad Ósea , Enfermedades Óseas/diagnóstico , Enfermedades Óseas Metabólicas/terapia , Huesos/patología , Femenino , Cuello Femoral/patología , Fracturas Óseas/patología , Humanos , Inmunosupresores/uso terapéutico , Fallo Hepático/terapia , Trasplante de Hígado/tendencias , Masculino , Persona de Mediana Edad , Osteoporosis , Complicaciones Posoperatorias , Prevalencia , Estudios Prospectivos , Vitamina D/químicaRESUMEN
BACKGROUND: Osteoporosis resulting from decreased bone formation is a common complication in patients with chronic cholestasis. Lithocholic acid (LCA) and bilirubin may play a role in osteoporosis given that both substances have detrimental effects on survival of human osteoblasts, the cells involved in bone formation. AIMS: As ursodeoxycholic acid (UDCA) improves cholestasis, we have assessed if this bile acid may neutralize the harmful effects of LCA, bilirubin and sera from jaundiced patients on osteoblastic cells. METHODS: The experiments were performed in primary human osteoblasts and human osteosarcoma cell line (Saos-2) at different times and concentrations of UDCA, LCA, cholic acid (CA), bilirubin and sera from jaundiced patients to assess cell viability, differentiation and mineralization. RESULTS: UDCA significantly decreased cell survival at concentrations 10 times higher (1 mM) than that observed with LCA, whereas CA did not decrease osteoblast survival. UDCA (100 µM) neutralized the damaging effects of bilirubin (50 µM) and sera from jaundiced patients on survival. Moreover, UDCA (1 µM and 10 µM) increased osteoblast differentiation in cells treated with harmful concentrations of LCA or bilirubin. UDCA (100 µM) increased cell differentiation in osteoblasts cultured with a mix of serum from cholestatic patients by 23%. Furthermore, UDCA increased osteoblast mineralization by 35% and neutralized the negative consequences of 50 µM bilirubin. CONCLUSIONS: UDCA increases osteoblast differentiation and mineralization, and neutralizes the detrimental effects of lithocholic acid, bilirubin and sera from jaundiced patients on osteoblastic cells. Therefore, UDCA may exert a favourable effect on bone in patients which chronic cholestasis.
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Bilirrubina/antagonistas & inhibidores , Colestasis/complicaciones , Osteoblastos/citología , Osteoporosis/etiología , Osteoporosis/metabolismo , Ácido Ursodesoxicólico/farmacología , Bilirrubina/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Colestasis/tratamiento farmacológico , Humanos , Ictericia/sangre , Ácido Litocólico/metabolismo , Osteoblastos/efectos de los fármacos , Estadísticas no ParamétricasRESUMEN
This cross-sectional study evaluated the distribution of serum cross-linked C-telopeptides of collagen type I (ßCTXs) in postmenopausal women, the characteristics of bone remodeling, and the factors influencing this bone marker, especially the use of anti-osteoporotic drugs. Women (n = 4,175) aged 59-70 years randomly selected from the community were invited to participate, measuring ßCTXs and lumbar and femoral bone mineral density at recruitment. Risk factors for osteoporosis and the use of anti-osteoporotic treatment were collected with a structured questionnaire. We evaluated the percentage of women with increased (ßCTXs >0.620 ng/mL) and decreased bone turnover (ßCTXs <0.100 ng/mL) and those reaching the so-called treatment target (values of ßCTXs within the lower half of the reference range for healthy young premenopausal women). Two thousand nine hundred sixty-eight women (70 %) participated (2,405 non-treated and 563 treated). Increased and decreased bone turnover was observed in 16.4 and 1.8 %, respectively, of non-treated women with significant differences compared with treated women (9.7 and 14.2 %, respectively, p < 0.001); 28 % of non-treated osteoporotic individuals had increased bone turnover versus 14 % of osteopenic participants and 8.8 % of women with normal bone density (p < 0.001). Women receiving bisphosphonates presented the highest percentages of decreased bone turnover (27 %) and ßCTXs (43 %) within the treatment target. Increased bone turnover is observed in 16.4 % of non-treated postmenopausal women and is more frequent in individuals with osteoporosis, whereas decreased bone turnover is unusual. Most participants taking bisphosphonates had values within the treatment target, but nearly one quarter had decreased bone turnover.
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Colágeno Tipo I/sangre , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/tratamiento farmacológico , Péptidos/sangre , Anciano , Índice de Masa Corporal , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Demografía , Diabetes Mellitus/sangre , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatologíaRESUMEN
BACKGROUND: X-linked hypophosphatemic osteomalacia (XLH) is an inherited disorder that can cause highly disabling musculoskeletal comorbidities in adulthood. OBJECTIVE: To analyze the clinical-radiological characteristics, comorbidities and complications associated with the disease and treatment in an adult population with XLH. METHOD: Retrospective study of patients treated for XLH in a rheumatology department in the last 10 years, evaluating the clinical-radiological findings, comorbidities and associated complications. RESULTS: Five patients between 39 and 75 years of age were included. All had short stature, osteoarticular symptoms and radiological enthesopathy. Four patients had early degenerative arthropathy of the knees and hips, and dental alterations associated with their disease. All patients older than 50 years required some type of prosthetic replacement. Two patients had femoral stress fractures, one had renal lithiasis and another developed tertiary hyperparathyroidism. CONCLUSIONS: Musculoskeletal manifestations are frequent and disabling in the adult population with XLH, so proper diagnosis and management from childhood are essential to prevent the development of complications in adulthood associated with this disease.
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Raquitismo Hipofosfatémico Familiar , Enfermedades Genéticas Ligadas al Cromosoma X , Osteomalacia , Humanos , Adulto , Niño , Osteomalacia/etiología , Estudios Retrospectivos , Raquitismo Hipofosfatémico Familiar/complicaciones , Raquitismo Hipofosfatémico Familiar/diagnóstico , Raquitismo Hipofosfatémico Familiar/terapia , Radiografía , Factores de Crecimiento de FibroblastosRESUMEN
UNLABELLED: Low bone formation is considered to be the main feature in osteoporosis associated with cholestatic and end-stage liver diseases, although the consequences of retained substances in chronic cholestasis on bone cells have scarcely been studied. Therefore, we analyzed the effects of bilirubin and serum from jaundiced patients on viability, differentiation, mineralization, and gene expression in the cells involved in bone formation. The experiments were performed in human primary osteoblasts and SAOS-2 human osteosarcoma cells. Unconjugated bilirubin or serum from jaundiced patients resulted in a dose-dependent decrease in osteoblast viability. Concentrations of bilirubin or jaundiced serum without effects on cell survival significantly diminished osteoblast differentiation. Mineralization was significantly reduced by exposure to 50 µM bilirubin at all time points (from -32% to -55%) and jaundiced sera resulted in a significant decrease on cell mineralization as well. Furthermore, bilirubin down-regulated RUNX2 (runt-related transcription factor 2) gene expression, a basic osteogenic factor involved in osteoblast differentiation, and serum from jaundiced patients significantly up-regulated the RANKL/OPG (receptor activator of nuclear factor-κB ligand/osteoprotegerin) gene expression ratio, a system closely involved in osteoblast-induced osteoclastogenesis. CONCLUSION: Besides decreased cell viability, unconjugated bilirubin and serum from jaundiced patients led to defective consequences on osteoblasts. Moreover, jaundiced serum up-regulates the system involved in osteoblast-induced osteoclastogenesis. These results support the deleterious consequences of increased bilirubin in advanced chronic cholestasis and in end-stage liver diseases, resulting in disturbed bone formation related to osteoblast dysfunction.