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1.
Am J Orthod Dentofacial Orthop ; 156(4): 555-565, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31582127

RESUMEN

A common dilemma when treating anterior open bite is understanding its etiology. Idiopathic condylar resorption (ICR) can cause open bite in affected individuals. Although it is prudent to not treat patients with ICR until active resorption has ceased, orthodontists may begin treating them because anterior open bite from ICR may not appear before or during their orthodontic treatment. This article reports a 12-year-old female who was diagnosed with ICR 10 months after completion of her orthodontic treatment for a Class II Division 1 malocclusion. When a young patient with a high mandibular angle and previous skeletal or dental Class II malocclusion returns with an open bite during the retention phase, the patient's condyles must be carefully examined to determine whether any temporomandibular joint disorder, such as ICR, is present. Currently, the controversy over the cause and the cure for ICR is continuing to challenge orthodontists in diagnoses and treatments. Orthodontists should closely monitor and offer informed treatment options to patients with risk factors for ICR or signs of its pathology that might develop at any stage of orthodontic treatment, including the retention period.


Asunto(s)
Resorción Ósea/complicaciones , Resorción Ósea/terapia , Maloclusión de Angle Clase II/terapia , Cóndilo Mandibular/patología , Enfermedades Mandibulares/patología , Enfermedades Mandibulares/terapia , Mordida Abierta/etiología , Mordida Abierta/terapia , Ortodoncia Correctiva/métodos , Trastornos de la Articulación Temporomandibular/terapia , Resorción Ósea/diagnóstico por imagen , Cefalometría , Niño , Terapia Combinada , Estética Dental , Femenino , Humanos , Maloclusión de Angle Clase II/diagnóstico por imagen , Enfermedades Mandibulares/diagnóstico por imagen , Mordida Abierta/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Resultado del Tratamiento
2.
Clin Sci (Lond) ; 133(18): 2005-2018, 2019 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-31519791

RESUMEN

The angiotensin-converting enzyme 2 (ACE2)-angiotensin 1-7 (A1-7)-A1-7 receptor (Mas) axis plays a protective role in the renin-angiotensin system (RAS). We recently found that ACE2 knockout (ACE2KO) mice exhibit earlier aging-associated muscle weakness, and that A1-7 alleviates muscle weakness in aging mice. In the present study, we investigated the role of the A1-7-Mas pathway in the effect of ACE2 on physiological aging. Male wild-type, ACE2KO, and Mas knockout (MasKO) mice were subjected to periodical grip strength measurement, followed by administration of A1-7 or vehicle for 4 weeks at 24 months of age. ACE2KO mice exhibited decreased grip strength after 6 months of age, while grip strength of MasKO mice was similar to that of wild-type mice. A1-7 improved grip strength in ACE2KO and wild-type mice, but not in MasKO mice. Muscle fibre size was smaller in ACE2KO mice than that in wild-type and MasKO mice, and increased with A1-7 in ACE2KO and WT mice, but not in MasKO mice. Centrally nucleated fibres (CNFs) and expression of the senescence-associated gene p16INK4a in skeletal muscles were enhanced only in ACE2KO mice and were not altered by A1-7. ACE2KO mice, but not MasKO mice, exhibited thinning of peripheral fat along with increased adipose expression of p16INK4a A1-7 significantly increased bone volume in wild-type and ACE2KO mice, but not in MasKO mice. Our findings suggest that the impact of ACE2 on physiological aging does not depend on the endogenous production of A1-7 by ACE2, while overactivation of the A1-7-Mas pathway could alleviate sarcopenia and osteoporosis in aged mice.


Asunto(s)
Envejecimiento/patología , Angiotensina I/uso terapéutico , Resorción Ósea/tratamiento farmacológico , Debilidad Muscular/tratamiento farmacológico , Fragmentos de Péptidos/uso terapéutico , Peptidil-Dipeptidasa A/deficiencia , Tejido Adiposo/patología , Angiotensina I/farmacología , Animales , Peso Corporal/efectos de los fármacos , Resorción Ósea/complicaciones , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Miembro Anterior/fisiopatología , Eliminación de Gen , Fuerza de la Mano , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Debilidad Muscular/complicaciones , Debilidad Muscular/diagnóstico por imagen , Músculos/diagnóstico por imagen , Músculos/efectos de los fármacos , Músculos/patología , Tamaño de los Órganos/efectos de los fármacos , Factor de Transcripción PAX3/metabolismo , Fragmentos de Péptidos/farmacología , Peptidil-Dipeptidasa A/metabolismo , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Factores de Tiempo
3.
PLoS One ; 14(8): e0221056, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31469844

RESUMEN

OBJECTIVE: Aseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15-20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists. DESIGN: The inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry. RESULTS: AL tissues had elevated levels of TNF-family members sTNFR2, TNFSF14, sFasL, sBAFF, cytokines/chemokines IL8, CCL2, IL1RA/IL36, sIL6R, and growth factors sAREG, CSF1, comparing to non-AL. High interindividual variability in protein levels was evident particularly in non-AL. Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between AL and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts. The source of elevated inflammatory molecules was macrophages and multinucleated osteoclast-like cells in AL and histiocytes and osteoclast-like cells in non-AL tissues, respectively. All proteins were present in higher levels in osteoclast-like cells than in macrophages. CONCLUSIONS: Our study revealed a differential inflammation signature between AL and non-AL stages of TKA. It also highlighted the unique patient's response to TKA in non-AL stages. Further confirmation of our preliminary results on a larger cohort is needed. Analysis of the time-axis of processes ongoing around TKA implantation may help to understand the mechanisms driving periprosthetic bone resorption needed for diagnostic/preventative strategies.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Resorción Ósea/fisiopatología , Citocinas/metabolismo , Inflamación/metabolismo , Falla de Prótesis/efectos adversos , Anciano , Anciano de 80 o más Años , Resorción Ósea/complicaciones , Resorción Ósea/metabolismo , Resorción Ósea/cirugía , Femenino , Histiocitos/metabolismo , Histiocitos/patología , Humanos , Inflamación/complicaciones , Inflamación/fisiopatología , Inflamación/cirugía , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Persona de Mediana Edad , Osteoclastos/metabolismo , Osteoclastos/patología , Reoperación
4.
J Shoulder Elbow Surg ; 28(11): 2128-2138, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31272889

RESUMEN

BACKGROUND: The incidence of medial calcar resorption has been shown to be common after uncemented total shoulder arthroplasty (TSA). With etiologies including stress shielding, debris-induced osteolysis, and infection, the clinical impact of medial calcar resorption has not been specifically examined. The purpose of this study was to determine whether resorption is associated with inferior outcomes or higher rates of radiographic loosening in TSA patients. METHODS: We conducted a retrospective review of TSA patients with minimum 2-year clinical follow-up. Patient-reported and functional outcome measures were recorded preoperatively and postoperatively. Postoperative radiographs were evaluated for glenoid and humeral component loosening. A new calcar resorption grading system was introduced to quantify the degree of resorption and assess the progression. RESULTS: A total of 171 patients met the inclusion criteria, with average clinical and radiographic follow-up periods of 50 and 46 months, respectively. Calcar resorption was identified in 110 patients (64.3%). No significant overall differences were observed between the patients with and without calcar resorption. Subgroup analysis showed that patients with grade 3 resorption had a higher incidence of glenoid radiolucencies (50%, P = .001) and patients with a progression from grade 1 to grade 3 had higher incidences of glenoid (50%, P = .003) and humeral (9%, P = .039) radiolucencies. CONCLUSION: Medial calcar resorption following TSA with a standard-length press-fit humeral component is common. Overall, no differences in patient-reported outcome measures or radiographic loosening were found compared with patients without calcar resorption. However, grade 3 calcar resorption and more dramatic progression of resorption should raise the suspicion of prosthetic loosening.


Asunto(s)
Artroplastía de Reemplazo de Hombro/efectos adversos , Resorción Ósea/complicaciones , Resorción Ósea/diagnóstico por imagen , Húmero/diagnóstico por imagen , Falla de Prótesis/etiología , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Radiografía , Estudios Retrospectivos , Escápula/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/fisiopatología , Articulación del Hombro/cirugía , Prótesis de Hombro
5.
Nat Commun ; 10(1): 2958, 2019 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-31273195

RESUMEN

RNAi-based bone anabolic gene therapy has demonstrated initial success, but many practical challenges are still unmet. Here, we demonstrate that a recombinant adeno-associated virus 9 (rAAV9) is highly effective for transducing osteoblast lineage cells in the bone. The adaptor protein Schnurri-3 (SHN3) is a promising therapeutic target for osteoporosis, as deletion of shn3 prevents bone loss in osteoporotic mice and short-term inhibition of shn3 in adult mice increases bone mass. Accordingly, systemic and direct joint administration of an rAAV9 vector carrying an artificial-microRNA that targets shn3 (rAAV9-amiR-shn3) in mice markedly enhanced bone formation via augmented osteoblast activity. Additionally, systemic delivery of rAAV9-amiR-shn3 in osteoporotic mice counteracted bone loss and enhanced bone mechanical properties. Finally, we rationally designed a capsid that exhibits improved specificity to bone by grafting the bone-targeting peptide motif (AspSerSer)6 onto the AAV9-VP2 capsid protein. Collectively, our results identify a bone-targeting rAAV-mediated gene therapy for osteoporosis.


Asunto(s)
Resorción Ósea/complicaciones , Resorción Ósea/prevención & control , Huesos/metabolismo , Proteínas de Unión al ADN/metabolismo , Dependovirus/metabolismo , Silenciador del Gen , Osteoporosis/complicaciones , Animales , Resorción Ósea/patología , Huesos/virología , Cápside/metabolismo , Cartílago/virología , Modelos Animales de Enfermedad , Eliminación de Gen , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Serogrupo
6.
Am J Orthod Dentofacial Orthop ; 156(1): 125-136, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31256825

RESUMEN

This case report describes the successful treatment of a 14-year-old girl with severe bilateral idiopathic condylar resorption and resultant mandibular retrusion, increased overjet, and anterior open bite. The nonextraction treatment plan included (1) aligning and leveling the teeth in both arches, (2) performing Le Fort I maxillary osteotomy, bilateral condylectomy, and mandibular joint replacement, and (3) postsurgical correction of the malocclusion. The orthodontic treatment was initiated with the use of custom lingual appliances followed by orthognathic surgery planned with virtual surgical planning. Patient-fitted and customized temporomandibular joint implants were designed and manufactured based on the patient's stereolithic bone anatomic model. Treatment was concluded with detailed orthodontic finishing. Optimum esthetic and functional results were achieved with the cooperation of 2 specialties and the use of state-of-the-art technology.


Asunto(s)
Tirantes , Prótesis Articulares , Cóndilo Mandibular/cirugía , Mordida Abierta/cirugía , Mordida Abierta/terapia , Ortodoncia Correctiva/métodos , Procedimientos Quirúrgicos Ortognáticos/métodos , Trastornos de la Articulación Temporomandibular/terapia , Adolescente , Puntos Anatómicos de Referencia , Resorción Ósea/complicaciones , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/cirugía , Resorción Ósea/terapia , Cefalometría , Estética Dental , Femenino , Humanos , Imagenología Tridimensional , Mandíbula/cirugía , Cóndilo Mandibular/diagnóstico por imagen , Maxilar/cirugía , Mordida Abierta/diagnóstico por imagen , Aparatos Ortodóncicos , Aparatos Ortodóncicos Fijos , Ortodoncia Correctiva/instrumentación , Osteotomía , Planificación de Atención al Paciente , Radiografía Panorámica , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/cirugía , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/cirugía , Resultado del Tratamiento
7.
Am J Orthod Dentofacial Orthop ; 155(4): 560-571, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30935611

RESUMEN

INTRODUCTION: We report the successful treatment of a 38-year-old woman with bilateral idiopathic condylar resorption and anterior open bite. She had incompetent lips, a gummy smile, increased lower facial height, high mandibular plane angle, skeletal and dental Class II malocclusion with mild mandibular crowding, increased overjet, and mandibular midline deviation to the right. METHODS: The treatment plan included: (1) presurgical alignment and leveling of the teeth in both arches; (2) jaw motion tracking (JMT) to detect mandibular movement; (3) 3-piece maxillary osteotomies with mandibular reconstruction and bilateral coronoidectomies; and (4) postsurgical correction of the malocclusion. The orthodontic treatment was performed with the use of custom lingual braces and clear brackets and the orthognathic surgery was planned with the use of virtual surgical planning. RESULTS: The idiopathic condylar resorption and anterior open bite were treated, crowding was eliminated in the lower anterior segment, correction of skeletal and dental Class II malocclusion was obtained, mandibular plane angle was reduced, and facial profile improved. CONCLUSIONS: The results suggest that esthetic and functional results can be achieved with the cooperation of 2 specialties and with the use of state-of-the-art technology.


Asunto(s)
Resorción Ósea/cirugía , Mordida Abierta/cirugía , Aparatos Ortodóncicos Fijos , Trastornos de la Articulación Temporomandibular/cirugía , Adulto , Resorción Ósea/complicaciones , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/terapia , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Imagenología Tridimensional , Mordida Abierta/complicaciones , Mordida Abierta/diagnóstico por imagen , Mordida Abierta/terapia , Aparatos Ortodóncicos , Ortodoncia Correctiva/instrumentación , Ortodoncia Correctiva/métodos , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/terapia
8.
J Bone Miner Metab ; 37(5): 796-804, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30712064

RESUMEN

In patients with chronic kidney disease (CKD) or those undergoing hemodialysis, pathological calcific deposition known as ectopic calcification occurs in soft tissue, resulting in a life-threatening disorder. A potent and effective inhibitor of ectopic calcification is eagerly expected. In the current study, the effects of FYB-931, a novel bisphosphonate compound synthesized for the prevention of ectopic calcification, were compared with those of etidronate using both in vitro and in vivo models. In vitro, FYB-931 inhibited calcification of human aortic smooth muscle cells induced by high phosphate medium in a concentration-dependent manner, and the effect was slightly more potent than that of etidronate. In vivo, rats were administered with three subcutaneous injections of vitamin D3 to induce vascular calcification, and were given FYB-931 (1.5, 5, or 10 mg/kg) or etidronate (9, 30, or 60 mg/kg) orally once daily for 14 days. The increased aortic phosphorus content as an index of vascular calcification was inhibited by both FYB-931 and etidronate in a dose-dependent manner; however, FYB-931 was 10 times more potent than etidronate. FYB-931 inhibited serum tartrate-resistant acid phosphatase (TRACP) activity as a bone resorption marker 5.2 times more potently than etidronate. FYB-931, but not etidronate, significantly decreased serum phosphorus levels. The preferential inhibition of aortic calcification by FYB-931 suggested that possible additional effect including a decline in serum phosphorus may lead to an advantage in terms of its efficacy.


Asunto(s)
Aorta/patología , Colecalciferol/uso terapéutico , Difosfonatos/uso terapéutico , Calcificación Vascular/tratamiento farmacológico , Animales , Biomarcadores/sangre , Resorción Ósea/sangre , Resorción Ósea/complicaciones , Resorción Ósea/patología , Células Cultivadas , Colecalciferol/farmacología , Difosfonatos/química , Difosfonatos/farmacología , Ácido Etidrónico/farmacología , Ácido Etidrónico/uso terapéutico , Humanos , Masculino , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Ratas Wistar , Fosfatasa Ácida Tartratorresistente/metabolismo , Calcificación Vascular/sangre , Calcificación Vascular/complicaciones , Calcificación Vascular/patología
9.
Res Vet Sci ; 123: 129-134, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30641472

RESUMEN

People with calcium oxalate (CaOx) urolithiasis and idiopathic hypercalciuria (IH) often have evidence of increased bone resorption, but bone turnover has not previously been investigated in dogs with these conditions. The aim of this study was to determine whether a marker of bone resorption, ß-crosslaps, differs between dogs with CaOx urolithiasis and IH compared to controls. This retrospective, cross-sectional study used a canine specific ELISA to measure ß-crosslaps concentrations in stored frozen serum samples from 20 dogs with CaOx urolithiasis and IH and 20 breed-, sex-, and age-matched stone-free controls (18 Miniature Schnauzers, 14 Bichons Frise, and 8 Shih Tzus). Dogs with CaOx urolithiasis and IH had lower ß-crosslaps concentrations relative to controls (P = .0043), and ß-crosslaps had a moderate negative correlation with urinary calcium-to-creatinine ratios (r = -0.44, P = .0044). Miniature Schnauzers had lower ß-crosslaps concentrations than the other two breeds (P = .0035). The ELISA had acceptable intra-assay precision, but concentrations decreased when samples were repeatedly assayed over time. Assay recovery rates were also below acceptance criteria. In conclusion, Miniature Schnauzers, Bichons Frise, and Shih Tzus with CaOx urolithiasis and IH have evidence of decreased bone resorption compared to stone-free controls. This suggests that other causes of IH, such as intestinal hyperabsorption of calcium, underlie risk for CaOx urolithiasis in these breeds. Results should be confirmed in larger populations and with other ß-crosslaps assays and additional biomarkers of bone turnover. The stability of canine serum ß-crosslaps after freeze-thaw cycles and storage at various temperatures requires investigation.


Asunto(s)
Resorción Ósea/veterinaria , Oxalato de Calcio , Enfermedades de los Perros/etiología , Hipercalciuria/veterinaria , Nefrolitiasis/veterinaria , Animales , Resorción Ósea/complicaciones , Resorción Ósea/patología , Estudios Transversales , Enfermedades de los Perros/patología , Perros , Femenino , Humanos , Hipercalciuria/complicaciones , Hipercalciuria/patología , Masculino , Nefrolitiasis/complicaciones , Nefrolitiasis/patología , Estudios Retrospectivos
10.
Bone ; 118: 20-31, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29604350

RESUMEN

High fat diets can have detrimental effects on the skeleton as well as cause intestinal dysbiosis. Exercise prevents high fat (HF) diet-induced obesity and also improves bone density and prevents the intestinal dysbiosis that promotes energy storage. Previous studies indicate a link between intestinal microbial balance and bone health. Therefore, we examined whether exercise could prevent HF-induced bone pathology in male mice and determined whether benefits correlate to changes in host intestinal microbiota. Male C57Bl/6 mice were fed either a low fat diet (LF; 10 kcal% fat) or a HF diet (60 kcal% fat) and put under sedentary or voluntary exercise conditions for 14 weeks. Our results indicated that HF diet reduced trabecular bone volume, when corrected for differences in body weight, of both the tibia (40% reduction) and vertebrae (25% reduction) as well and increased marrow adiposity (44% increase). More importantly, these effects were prevented by exercise. Exercise also had a significant effect on several cortical bone parameters and enhanced bone mechanical properties in LF but not HF fed mice. Microbiome analyses indicated that exercise altered the HF induced changes in microbial composition by reducing the Firmicutes/Bacteriodetes ratio. This ratio negatively correlated with bone volume as did levels of Clostridia and Lachnospiraceae. In contrast, the abundance of several Actinobacteria phylum members (i.e., Bifidobacteriaceae) were positively correlated with bone volume. Taken together, exercise can prevent many of the negative effects of a high fat diet on male skeletal health. Exercise induced changes in microbiota composition could represent a novel mechanism that contributes to exercise induced benefits to bone health.


Asunto(s)
Adiposidad , Médula Ósea/patología , Resorción Ósea/prevención & control , Dieta Alta en Grasa/efectos adversos , Disbiosis/prevención & control , Condicionamiento Físico Animal , Animales , Biomarcadores/sangre , Resorción Ósea/sangre , Resorción Ósea/complicaciones , Resorción Ósea/fisiopatología , Hueso Esponjoso/patología , Hueso Esponjoso/fisiopatología , Hueso Cortical/patología , Hueso Cortical/fisiopatología , Disbiosis/sangre , Disbiosis/complicaciones , Microbioma Gastrointestinal , Masculino , Ratones Endogámicos C57BL , Obesidad/prevención & control , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogénesis
11.
J Bone Miner Metab ; 37(1): 81-89, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29335796

RESUMEN

Frailty is significantly associated with bone loss in the general population. However, it is unclear whether this association also exists in patients undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to assess the association between frailty and bone loss in patients undergoing hemodialysis. This cross-sectional study included 214 (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis three times per week, with a mean age of 67.1 years (women) and 66.8 years (men). Frailty was defined based on criteria set forth by the Cardiovascular Health Study (CHS)-19 (21.1%) women and 47 (37.9%) men were robust, 41 (45.6%) women and 43 (34.7%) men were pre-frail, and 30 (33.3%) women and 34 (27.4%) men were frail. For bone mass, quantitative ultrasound (QUS) parameters (speed of sound, broadband ultrasound attenuation, stiffness index) of the calcaneus were measured. The association between frailty and QUS parameters was determined separately for women and men using multivariate analysis of covariance (ANCOVA), with adjustments for clinical characteristics including age, body mass index, hemodialysis vintage, diabetes, current smoking, serum albumin, phosphate, corrected calcium, intact parathyroid hormone, and medication for CKD-MBD (vitamin D receptor activator, calcimimetics). ANCOVA revealed that all QUS parameters declined significantly with increasing levels of frailty in both sexes (P < 0.05). In conclusion, frailty (as defined by CHS criteria) should be considered a risk factor for bone loss in patients undergoing hemodialysis.


Asunto(s)
Resorción Ósea/complicaciones , Fragilidad/complicaciones , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Resorción Ósea/diagnóstico por imagen , Estudios Transversales , Femenino , Fragilidad/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Ultrasonografía
12.
Int J Biol Macromol ; 123: 314-321, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-30439432

RESUMEN

Potent anti-osteoporotic drugs have been developed over the past decades; however, the substantial need for treatments that can effectively and safely manage osteoporosis remains unmet. Barley leaf-derived products are one of best functional foods that can be used as nutritional supplements and detoxifiers in humans and are beneficial in improving bone disease. However, little information is available regarding the anti-osteoporotic effects of polysaccharides as the main component of barley leaf. This study aimed to clarify the beneficial effects of barley leaf (BLE0) polysaccharides on bone loss in ovariectomized mice and osteoclast differentiation in bone marrow-derived macrophages. BLE0 remarkably inhibited receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner. It also blocked RANKL-induced activation of osteoclastogenic signals including ERK and p38 and the expression of nuclear factor of activated T cells cytoplasmic 1, as a master regulator of osteoclast differentiation, leading to decreased expression of osteoclast-specific marker genes such as Atp6v0d2, DC-STAMP and cathepsin K. Micro-computed tomography revealed that a seven-week oral administration of BLE0 dramatically improved ovariectomy-induced trabecular bone loss. Anti-osteoporotic effects were confirmed using morphometric analysis. Taken together, BLE0 is a bioactive polysaccharide; it mitigates estrogen deficiency-induced bone loss by directly inhibiting osteoclast differentiation.


Asunto(s)
Resorción Ósea/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Polisacáridos/química , Animales , Células de la Médula Ósea/efectos de los fármacos , Resorción Ósea/complicaciones , Resorción Ósea/patología , Hordeum/química , Humanos , Macrófagos/efectos de los fármacos , Ratones , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis/complicaciones , Osteoporosis/patología , Ovariectomía , Hojas de la Planta/química , Polisacáridos/administración & dosificación
13.
Bone ; 120: 114-124, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30342225

RESUMEN

Although it is suggested that chronic obstructive pulmonary disease (COPD) and bone are related, almost all of the pathological mechanisms of COPD-related osteoporosis remain unknown. There is a mouse model showing a deterioration of bone quality after cigarette smoke exposure; however, in smoking exposure models, various factors exist that affect bone metabolism, such as smoking and body weight loss (muscle and fat mass loss). We considered it appropriate to use an elastase-induced emphysema model to exclude factors influencing bone metabolism and to investigate the influence of pulmonary emphysema on bone metabolism. The purpose of this study was to establish a COPD/emphysema-related osteoporosis mouse model by using the elastase-induced emphysema model. The lumbar vertebrae and femurs/tibiae exhibited trabecular bone loss and impaired osteogenic activity in 24-week-old male elastase-induced emphysema model mice. In addition, the model mice showed atrophy of type I muscle fibers without atrophy of type II muscle fibers. We believe that the mice described in this experimental protocol will be accepted as a COPD/emphysema-related osteoporosis mouse model and contribute to further investigations.


Asunto(s)
Resorción Ósea/complicaciones , Fibras Musculares Esqueléticas/patología , Osteogénesis , Osteoporosis/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/complicaciones , Animales , Atrofia , Biomarcadores/metabolismo , Peso Corporal , Densidad Ósea , Huesos/metabolismo , Huesos/patología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Modelos Animales de Enfermedad , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Tamaño de los Órganos , Elastasa Pancreática , Microtomografía por Rayos X
14.
Bone ; 120: 482-486, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30572144

RESUMEN

Denosumab is an anti-RANKL antibody that is commonly used for the treatment of osteoporosis; in oncology, bisphosphonates and denosumab have become the standard therapies for the treatment and prevention of skeletal complications in patients with myeloma and solid tumors. In recent years, excessive bone remodeling following the discontinuation of denosumab has raised concerns. Several cases of hypercalcemia have been reported after the discontinuation of high-dose denosumab (120 mg every 4 weeks), mainly in children. In this study, we report a new case of severe refractory hypercalcemia in a 54-year-old woman who received high-dose denosumab for 5 years as an adjuvant therapy for breast cancer. She is currently in remission and undergoing treatment with anastrazole, an aromatase inhibitor. The peculiarities of this case are the presence of associated bone pain with subperiosteal bone resorption on hand X-rays, and diffuse, long bone diaphyseal uptake on a bone scan. Hyperparathyroidism has been ruled out, and existing evidence suggests that this high-level of bone remodeling could be due to a rebound hyperactivation of the RANKL pathway. In addition to rehydration, repeated use of i.v. bisphosphonates was required to control recurrent hypercalcemia. As hypercalcemia is a serious metabolic complication, a gradual dose reduction should be considered when interruption of high dose denosumab therapy is planned.


Asunto(s)
Resorción Ósea/complicaciones , Hipercalcemia/complicaciones , Ligando RANK/metabolismo , Enfermedad Aguda , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/tratamiento farmacológico , Huesos/diagnóstico por imagen , Huesos/patología , Femenino , Humanos , Hipercalcemia/diagnóstico por imagen , Hipercalcemia/tratamiento farmacológico , Persona de Mediana Edad , Pamidronato/uso terapéutico
15.
J Transl Med ; 16(1): 306, 2018 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-30413166

RESUMEN

BACKGROUND: Diabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss. Simvastatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone. Therefore, we investigated effect of SIM on tibial and alveolar bone loss in type 1 diabetic rats with periodontitis. METHODS: Rats were divided into control (C), diabetes with periodontitis (DP), and diabetes with periodontitis treated with SIM (DPS) groups. DP and DPS groups were intravenously injected with streptozotocin (50 mg/kg), and C group was injected with citrate buffer. Seven days later (day 0), periodontitis was induced by ligatures of mandibular first molars. DP and DPS groups were orally administered vehicle or SIM (30 mg/kg) from day 0 to days 3, 10, or 20. Alveolar and tibial bone loss was measured using histological and m-CT analysis alone or in combination. Osteoclast number and sclerostin-positive osteocytes in tibiae were evaluated by tartrate-resistant acid phosphatase and immunohistochemical staining, respectively. Glucose, triglyceride (TG), cholesterol (CHO), and low-density lipoprotein (LDL) were evaluated. RESULTS: Consistent with diabetes induction, the DP group showed higher glucose and TG levels at all timepoints and higher CHO levels on day 20 than C group. Compared to the DP group, the DPS group exhibited reduced levels of glucose (day 3), TG (days 10 and 20), CHO, and LDL levels (day 20). Bone loss analysis revealed that the DP group had lower bone volume fraction, bone mineral density, bone surface density, and trabecular number in tibiae than C group at all timepoints. Interestingly, the DPS group exhibited elevation of these indices at early stages compared to the DP group. The DPS group showed reduction of osteoclasts (day 3) and sclerostin-positive osteocytes (days 3 and 20) compared with the DP group. There was no difference in alveolar bone loss between DP and DPS groups. CONCLUSIONS: These results suggest that SIM attenuates tibial, but not alveolar bone loss in type 1 diabetic rats with periodontitis. Moreover, attenuation of tibial bone loss by SIM may be related to inhibition of osteoclast formation and reduction of sclerostin expression.


Asunto(s)
Resorción Ósea/complicaciones , Resorción Ósea/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Periodontitis/complicaciones , Simvastatina/uso terapéutico , Tibia/patología , Pérdida de Hueso Alveolar/sangre , Pérdida de Hueso Alveolar/complicaciones , Pérdida de Hueso Alveolar/tratamiento farmacológico , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Proteínas Morfogenéticas Óseas/metabolismo , Resorción Ósea/sangre , Resorción Ósea/patología , Colesterol/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 1/sangre , Ayuno/sangre , Marcadores Genéticos , Lipoproteínas LDL/sangre , Masculino , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Periodontitis/sangre , Ratas Endogámicas F344 , Simvastatina/farmacología , Tibia/efectos de los fármacos , Triglicéridos/sangre
16.
Biomolecules ; 8(3)2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-30071694

RESUMEN

The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.


Asunto(s)
Resorción Ósea/metabolismo , Calcio/metabolismo , Animales , Resorción Ósea/complicaciones , Humanos , Inflamación/complicaciones , Interleucina-1/biosíntesis
17.
PLoS One ; 13(8): e0202583, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30118518

RESUMEN

Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated with erosions, and with juxta-articular and systemic bone loss. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are independently associated with erosions. However, we do not know if they are also associated with juxta-articular and systemic bone loss. Here, we have addressed this question with data from 548 early arthritis (EA) patients. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti-CarPA positive patients did not show significant differences in BMD Z-scores with the negative patients. Nevertheless, this result was due to the similarity between negative and low-positive (below the median of the positive) patients, whereas the high-positive patients showed significant decrease of BMD at LS (ß = -0.39, p = 0.01) and TH (ß = -0.30, p = 0.02); but not at the juxta-articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in an analysis that showed significantly lower BMD Z-scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive subgroup. However, the similar coefficients of regression between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (ß = -0.50 vs. -0.52 at LS, and ß = -0.37 vs. -0.30 at TH) suggested an independent association. Overall, these results support a contribution of anti-CarPA to systemic bone loss in EA patients.


Asunto(s)
Artritis Reumatoide/fisiopatología , Densidad Ósea , Resorción Ósea/fisiopatología , Osteólisis/fisiopatología , Absorciometría de Fotón , Adulto , Anciano , Anticuerpos Antiproteína Citrulinada/sangre , Anticuerpos Antiproteína Citrulinada/inmunología , Anticuerpos Antiidiotipos/sangre , Anticuerpos Antiidiotipos/inmunología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico por imagen , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Resorción Ósea/sangre , Resorción Ósea/complicaciones , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Masculino , Articulación Metacarpofalángica/fisiopatología , Persona de Mediana Edad , Osteoclastos/inmunología , Osteoclastos/patología , Osteólisis/complicaciones , Osteólisis/diagnóstico por imagen , Carbamilación de Proteína/inmunología
18.
Dis Model Mech ; 11(9)2018 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-30154079

RESUMEN

Paget's disease of bone (PDB) is an age-related metabolic bone disorder, characterised by focally increased and disorganised bone remodelling initiated by abnormal and hyperactive osteoclasts. The germline P392L mutation of SQSTM1 (encoding p62) is a strong genetic risk factor for PDB in humans, and the equivalent mutation in mice (P394L) causes a PDB-like disorder. However, it is unclear why pagetic lesions become more common with age. Here, we assessed the effect of the p62 P394L mutation on osteoclastogenesis and bone morphometry in relation to ageing, the natural history of lesion progression in p62P394L mice and the effect of zoledronic acid (ZA) on lesion development. p62P394L+/+ osteoclast precursors had increased sensitivity to RANKL (also known as TNFSF11) compared with wild-type (WT) cells, and the sensitivity further increased in both genotypes with ageing. Osteoclastogenesis from 12-month-old p62P394L+/+ mice was twofold greater than that from 3-month-old p62P394L+/+ mice (P<0.001) and three-fold greater than that from age-matched WT littermates. The p62P394L+/+ mice lost 33% more trabecular bone volume in the long bones by 12 months compared with WT mice (P<0.01), and developed pagetic-like lesions in the long bones which progressed with ageing. ZA prevented the development of pagetic-like lesions, and increased trabecular bone volume tenfold compared with vehicle by 12 months of age (P<0.01). This demonstrates that ageing has a pro-osteoclastogenic effect, which is further enhanced by the p62 P394L mutation, providing an explanation for the increased penetrance of bone lesions with age in this model. Lesions are prevented by ZA, providing a rationale for early intervention in humans.


Asunto(s)
Resorción Ósea/patología , Osteítis Deformante/tratamiento farmacológico , Osteítis Deformante/prevención & control , Proteína Sequestosoma-1/genética , Ácido Zoledrónico/uso terapéutico , Envejecimiento/patología , Animales , Resorción Ósea/complicaciones , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Huesos/patología , Calcificación Fisiológica/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Ratones Mutantes , Mutación/genética , Tamaño de los Órganos , Osteítis Deformante/complicaciones , Osteítis Deformante/patología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Fenotipo , Ácido Zoledrónico/farmacología
19.
Bone ; 116: 8-21, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29990585

RESUMEN

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.


Asunto(s)
Bixaceae/química , Resorción Ósea/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Tocotrienoles/uso terapéutico , Adiponectina/metabolismo , Animales , Resorción Ósea/complicaciones , Resorción Ósea/diagnóstico por imagen , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/efectos de los fármacos , Hueso Esponjoso/patología , Carotenoides/administración & dosificación , Carotenoides/uso terapéutico , Dieta Alta en Grasa , Carbohidratos de la Dieta , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Inflamación/patología , Leptina/metabolismo , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/diagnóstico por imagen , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Ratas Wistar , Tocotrienoles/administración & dosificación , Tocotrienoles/farmacología , Microtomografía por Rayos X
20.
Bone ; 116: 1-7, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29969750

RESUMEN

Despite the potential biological importance of sympathetic activity in human bone metabolism, its effects on bone microarchitecture, a key determinant of bone quality, has not been thoroughly studied. In the present study, we investigated the lumbar spine trabecular bone score (TBS) as an indicator of skeletal deterioration in pheochromocytoma. Among 620 consecutive patients with newly diagnosed adrenal incidentaloma, 29 with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 266 with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 2.9% lower lumbar spine TBS than those without pheochromocytoma (P = 0.038). Moreover, urinary normetanephrine level, but not urinary metanephrine level, was inversely correlated with lumbar spine TBS (P = 0.009). Subjects in the highest urinary normetanephrine quartile showed markedly lower lumbar spine TBS than those in the lowest quartile (P = 0.018), in a dose-response manner across increasing urinary normetanephrine quartile categories (P for trend = 0.021). Consistent with the results of previous studies, subjects with pheochromocytoma had significantly lower bone mass at the lumbar spine and higher serum level of C-terminal telopeptide of type I collagen than controls (P = 0.013 and 0.002, respectively). These findings provide clinical evidence that catecholamine excess and the resultant sympathetic overstimulation in pheochromocytoma may contribute to bone fragility, especially in the trabecular bone, through a weak microarchitecture in addition to a lower bone mass and increased bone resorption, and support the possibility of pheochromocytoma as a secondary cause of osteoporosis.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/patología , Huesos/patología , Feocromocitoma/patología , Sistema Nervioso Simpático/patología , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/orina , Adulto , Anciano , Densidad Ósea , Resorción Ósea/complicaciones , Resorción Ósea/orina , Hueso Esponjoso/patología , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Normetanefrina/orina , Feocromocitoma/complicaciones , Feocromocitoma/orina , Factores de Riesgo , Adulto Joven
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