Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation.

OBJECTIVE: To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS: Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS: iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION: Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation，indicating it may be a potential treatment for inflammatory bone loss does in AS.

Effect of different doses of synthetic parathyroid hormone (1-34) on bone around implants: a preclinical rat model

Abstract The aim of this study was to evaluate the effect of a lower dose of parathyroid hormone- PTH (1-34) on osteogenic potential of bone healing around titanium implants inserted into the tibia of rats. A blind parallel study was conducted in 45 adult male Wistar rats. Each rat received one titanium implant (4.5 x 2.2 mm) and was randomly assigned to receive subcutaneous injections, three times/week for 30 days, of the following treatments: group 1 - 40 µg/kg of PTH (1-34) (n=15); group 2 - 2 µg/kg of PTH (1-34) (n=15) and; group 3 - only the vehicle required for hormone dissolution (n=15). Thirty days after surgery, the animals were sacrificed and specimens containing the implant and the surrounding bone were removed and processed for non-decalcified sections. The sections were evaluated according to the following histometric parameters: proportion of mineralized tissue (PMT) adjacent to the implant threads (500 µm band); bone filling within the limits of the threads (BF) and; bone-to-implant contact (BIC). For the cortical region, both hormone dosages (groups 1 and 2) promoted better results, for all parameters, when compared to control group (p<0.05). Similar results were observed for the BF parameter in the cancellous region (p=0.0394). Therefore, systemic administration of PTH (1-34) stimulates bone formation around titanium implants, even at low doses.

Resumo O objetivo deste estudo foi avaliar o efeito de uma menor dose de PTH (1-34) sobre o potencial osteogênico da cicatrização óssea ao redor de implantes de titânio inseridos na tíbia de ratos. Um estudo paralelo cego foi conduzido em 45 ratos Wistar machos adultos. Cada rato recebeu um implante de titânio (4,5 x 2,2 mm) e foi aleatoriamente designado para receber injeções subcutâneas, três vezes / semana por 30 dias, dos seguintes tratamentos: grupo 1 - 40 µg/kg de PTH (1-34) (n = 15); grupo 2 - 2 µg/kg de PTH (1-34) (n = 15) e; grupo 3 - apenas o veículo necessário para a dissolução do hormônio (n = 15). Trinta dias após a cirurgia, os animais foram sacrificados e os espécimes contendo o implante e o osso ao redor foram removidos e processados ​​para cortes não descalcificados. As seções foram avaliadas de acordo com os seguintes parâmetros histométricos: proporção de tecido mineralizado (PTM) adjacente aos fios do implante (banda de 500 µm); preenchimento ósseo dentro dos limites dos fios (PO) e; contato osso-implante (COI). Para a região cortical, ambas as dosagens hormonais (grupos 1 e 2) promoveram melhores resultados, para todos os parâmetros, quando comparados ao grupo controle (p<0,05). Resultados semelhantes foram observados para o parâmetro PO na região esponjosa (p = 0,0394). Portanto, a administração sistêmica de PTH (1-34) estimula a formação óssea ao redor de implantes de titânio, mesmo em doses baixas.

De la osteología a la osteomiología: tres décadas de aportes originales continuos al análisis biomecánico osteomuscular / From osteology to osteo-myology: three decades of continuous, original contributions to musculoskeletal biomechanical analysis

En consonancia con la orientación tradicional de nuestras investigaciones, la Osteología está incorporando progresivamente el análisis estructural-biomecánico óseo y las interacciones músculo-esqueléticas. En este artículo se sintetizan los aportes originales del CEMFoC a la Osteología moderna en el terreno biomecánico en forma didáctica, para que el lector aprecie sus posibles aplicaciones clínicas. Los hallazgos aportaron evidencias sucesivas en apoyo de dos proposiciones fundamentales: a) los huesos deben interpretarse como estructuras resistivas, biológicamente servocontroladas ("Los huesos tienden siempre a mantener un factor de seguridad que permite al cuerpo trabajar normalmente sin fracturarse" ­ Paradigma de Utah) y b) los huesos interactúan con su entorno mecánico, determinado principalmente por las contracciones musculares, en forma subordinada al entorno metabólico ("Los huesos son lo que los músculos quieren que sean, siempre que las hormonas lo permitan"). Los avances producidos se refieren, tanto cronológica como didácticamente, al conocimiento osteológico en general y al desarrollo de recursos novedosos para el diagnóstico no invasivo de fragilidad ósea, para distinguir entre osteopenias y osteoporosis, y para discriminar entre sus etiologías 'mecánica' y 'sistémica'. Finalmente, el nuevo conocimiento se integra en la proposición de un algoritmo diagnóstico para osteopenias y osteoporosis. El espíritu general de la presentación destaca que la evaluación osteomuscular dinámicamente integrada genera un nuevo espacio de análisis personalizado de los pacientes para la atención de cualquier osteopatía fragilizante con criterio biomecánico. (AU)

In consonance with the traditional spirit of our studies, skeletal research is being progressively focused on the structural-biomechanical analysis of bone and the muscle-bone interactions. In this article, the CEMFoC's members summarize their original findings in bone biomechanics and their potential clinical applications. These findings provided evidence supporting two fundamental hypotheses, namely, A. bones constitute resistive structures, which are biologically servo-controlled ('Bones tend to maintain a safety factor which allows the body to function normally avoiding fractures' ­ the 'Utah paradigm'), and B. the interactions of bones with their mechanical environment mainly are determined by the contraction of local muscles - 'bone-muscle units'), and are subordinated to the control of the metabolic environment ('Bones are what muscles wish them to be, provided that hormones allow for it'). The achievements in the field are presented in a chronological and didactical sequence concerning the general knowledge in Osteology and the development of novel resources for non-invasive diagnosis of bone fragility, aiming to distinguish between osteopenias and osteoporosis and the 'mechanical' and 'metabolic' etiology of these conditions. Finally, the integrated new knowledge is presented as supporting for a proposed diagnostic algorithm for osteopenias and osteoporosis. In general terms, the article highlights the dynamic evaluation of the musculoskeletal system as a whole, opening a new diagnostic field for a personalized evaluation of the patients affected by a boneweakening disease, based on functional and biomechanical criteria. (AU)

Effects of continual intermittent administration of parathyroid hormone on implant stability in the presence of osteoporosis: an in vivo study using resonance frequency analysis in a rabbit model

Abstract Objective: This study aimed to evaluate the effects of continual intermittent administration of parathyroid hormone (PTH) on implant stability in the presence of osteoporosis, using rabbit models. Material and Methods: Fifteen female New Zealand white rabbits underwent ovariectomy and were administered glucocorticoids to induce osteoporosis, following which they were divided into three groups. The first group received intermittent subcutaneous PTH for 4 weeks until implant placement (PTH1), while the second and third groups received PTH (PTH2) and saline (control), respectively, for 4 weeks before and after implant placement. After intermittent administration of PTH or saline, titanium implants were inserted into the left femoral epiphyses of all animals, and the implant stability quotient (ISQ) was measured immediately after placement to assess the primary stability and at 2 and 4 weeks after implant placement to assess osseointegration. At 4 weeks after implant placement, histological and histomorphometric evaluations were conducted and the bone area around the implant socket was measured as a ratio of the total bone area to the total tissue area. Results: Regarding primary stability, the ISQ values for the PTH1 and PTH2 groups were significantly higher than those for the control group (p<0.05). Concerning osseointegration, the ISQ values at 2 and 4 weeks were significantly higher for the PTH2 group than for the PTH1 and control (p<0.05) groups. Histological assessments showed a thicker and more trabecular bone around the implant sockets in the PTH2 specimens than in the PTH1 and control specimens. The bone area around the implant socket was significantly greater in the PTH2 group than in the PTH1 and control groups (p<0.05). Conclusions: Our results suggest that continual intermittent PTH administration before and after dental implant placement is effective for the achievement of favorable stability and osseointegration in the presence of osteoporosis.

Efectos divergentes del factor de crecimiento endotelial vascular, VEGF y el fragmento N-terminal de la proteína relacionada con la parathormona, PTHrP en células madre mesenquimales derivadas de tejido adiposo humano / No disponible

No disponible

Bisphosphonates, vitamin D, parathyroid hormone, and osteonecrosis of the jaw. Could there be a missing link?

BACKGROUND: It is estimated that over 190 million bisphosphonates have been prescribed worldwide. But this drug can produce adverse effects, of which osteonecrosis of the jaw and severe hypocalcemia are the most serious. It is evident that bisphosphonate administration affects multiple and diverse biochemical mediators related to bone metabolism. MATERIAL AND METHODS: This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. The imbalances generated by vitamin D and calcium deficiencies, together with their multiple systemic repercussions, have been widely researched but the outcomes of these imbalances in relation to bisphosphonate administration are not well known, and some research has indicated that they may be associated with osteonecrosis of the jaw (ONJ). RESULTS: The present review set out to explain the functioning of bone metabolism, the importance of different chemical mediators, the imbalances produced by incorrect use of this drug, in order to forewarn against the possible relation of these parameters with ONJ, whose physiopathology remains unknown. CONCLUSIONS: Medical and dental clinics should keep detailed anamneses of the use of vitamin D and calcium supplements, as it is of vital importance to maintain their correct levels in blood, given that these are related to ONJ as well as other adverse effects; this procedure is also necessary in order to ensure the correct use of the drug

No disponible

Influencia de la enfermedad renal crónica terminal en la aparición de pérdida de la integridad tisular / Influence of chronic kidney disease in the occurrence of loss of tissue integrity

Introducción: La calcifilaxis se caracteriza por calcificación de arteriolas, fibrosis y trombosis que conduce a la aparición de úlceras cutáneas isquémicas y necrosis, y afecta con mayor frecuencia a pacientes con enfermedad renal crónica terminal. El tratamiento de la calcifilaxis es variado, sin existir una modalidad terapéutica eficaz, y presenta mal pronóstico, principalmente por la sepsis secundaria a infección de las lesiones cutáneas. Objetivo: Conocer la producción científica sobre la calcifilaxis relacionada con la enfermedad renal crónica. Metodología: Se ha llevado a cabo una revisión bibliográfica con una búsqueda de bibliografía en las principales bases de datos PubMed/Medline, Scielo, Cuiden, ProQuest/Health and Medical Complete, IME y Google Académico. Resultados: Se seleccionaron 61 artículos para la realización del estudio: 19 artículos de revisión, 13 originales y 29 casos clínicos. Las variables estudiadas han sido las alteraciones en el metabolismo del fósforo, calcio y hormona paratiroidea, varios factores de riesgo, distribución de las lesiones, fallecimiento por sepsis, tratamiento médico y cuidados de enfermería. Los factores más influyentes en la aparición de calcifilaxis son las alteraciones en el metabolismo, obesidad, diabetes, hipertensión, baja albúmina sérica y toma de anticoagulantes. El tratamiento implica múltiples medidas terapéuticas, dirigidas al control de las alteraciones del metabolismo y la cura de las manifestaciones cutáneas. Conclusiones: La calcifilaxis es una entidad poco frecuente y con una elevada mortalidad. La patogénesis es desconocida y desde el punto de vista terapéutico, no existe un tratamiento específico, por lo que es fundamental un enfoque multidisciplinar, para su prevención y detección precoz (AU)

Introduction: Calciphylaxis is characterized by calcification of arterioles, fibrosis and thrombosis which leads to the onset of ischemic skin ulcers and necrosis, and most often affects in patients with end stage renal disease. Treatment of calciphylaxis is varied, without effective therapeutic modality and poor prognosis, mainly due to sepsis secondary to infection of the skin lesions. Objective: To know the scientific production on calciphylaxis related to chronic kidney disease. Methodology: A literature review was conducted with a literature search in the following databases: PubMed / Medline, Scielo, Cuiden, ProQuest / Health and Medical Complete, IME and Google Scholar. Results: Sixty-one articles were selected for the study: 19 review articles, 13 originals and 29 clinical cases. The variables studied were: alterations in the metabolism of phosphorus, calcium and parathyroid hormone, several risk factors, distribution of injuries, death due to sepsis, medical treatment and nursing care. The most influential factors in the development of calciphylaxis are alterations in metabolism, obesity, diabetes, hypertension, low serum albumin and taking anticoagulants. Treatment involves multiple therapeutic measures aimed at controlling the metabolic disorders and cure of cutaneous manifestations. Conclusion: Calciphylaxis is an uncommon event with high mortality. The pathogenesis is unknown and from a therapeutic point of view, there is no specific treatment, so that a multidisciplinary approach is essential for its prevention and early detection (AU)

Coexistence of glucocorticoid resistance and pseudohypoparathyroidism / Coexistencia de la resistencia a glucocorticoides y el pseudohipoparatiroidismo

We report for the first time the case of a young man who developed both glucocorticoid resistance and resistance to parathyroid hormone. Treatment with high doses of dexamethasone together with administration of calcium and calcitriol resulted in a significant improvement in the patient's condition. In this paper, we discuss in detail diagnostic and treatment strategies used on the patient and the impact on the course and outcome of both disorders. We associate the development of both these disorders with a possible inherited defect in the signal pathways common to glucocorticoid and parathyroid hormone receptors.

Por primera vez se reporta el caso de un joven que desarrolló resistencia a glucocorticoides y resistencia a la hormona paratiroidea. El tratamiento con altas dosis de dexametasona, junto con la administración de calcio y calcitriol, trajo como resultado una mejoría significativa de la condición del paciente. En este papel, se analiza en detalle el diagnóstico así como las estrategias de tratamiento del paciente, y su impacto en el curso y resultado de ambos trastornos. Se concluye que el desarrollo de ambos trastornos se halla asociado a un posible defecto hereditario en las vías de transducción de señales comunes a los receptores de las hormonas glucocorticoides y las hormonas paratiroideas.

Metabolismo del calcio / Calcium and its metabolism

El calcio es esencial tanto para las funciones intracelulares como para un crecimiento y desarrollo normal. El contenido en el organismo se regula fundamentalmente a través del tubo digestivo.El calcio es el electrólito más abundante en el cuerpo. Más del 90 por ciento del calcio del cuerpo se almacena en el esqueleto y en los dientes en forma de cristales de tipo de hidroxiapatita El 99 por ciento del calcio del esqueleto no es utilizable para la homeostasis inmediata y sólo un 1 por ciento del total de calcio está en el plasma y en el fluido extravascular. El calcio iónico, tanto plasmático como citosólico, juega un rol fundamental en la actividad celularGran cantidad de funciones vitales son mediadas por el calcio celular y sérico, por lo que no sorprende que las funciones del esqueleto y de la integridad dental se afecten en situaciones de su deficiencia relativa.Las deficiencias crónicas se manifiestan como raquitismo y osteomalacia en el niño pequeño y como osteoporosis en el adulto. Aún cuando la deposición de calcio y fósforo ocurre en el esqueleto hasta la juventud, las reservas de calcio y fósforo son lentamente depletadas en adultos mayores (sobretodo mujeres) llevando a la osteoporosis (AU)

Intermittent parathyroid hormone treatment can promote linear growth in the ovariectomized growing rat

To compare the effect of intermittent parathyroid hormone (PTH) treatment with that of estrogen treatment on epiphyseal growth in ovariectomized rats, 46 Sprague-Dawley female rats aged 9-10 weeks (about 200-220 g) were either ovariectomized or sham operated. From 6 weeks after ovariectomy (ovx), rats were daily injected with subcutaneous human recombinant PTH (1-84)-dosed 30 micrograms/kg (the low dose PTH-treated group) or 300 micrograms/kg (the high dose PTH-treated group), 17 beta-estradiol (the 17 beta-estradiol-treated group, 30 micrograms/kg) or vehicle (the ovx-alone group), 5 times a week for 4 weeks. The decalcified sections of the distal femoral epiphyseal plate were analyzed on light microscopy after H&E stain, and the lengths of the zones of proliferation, maturing and hypertrophic chondrocytes were measured. The length of the growth plate, the zone of proliferation and the zone of hypertrophic chondrocyte in the ovx-alone group were significantly shorter than those of the sham-operated group. The treatment of 17 beta-estradiol speeded up the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes even though the length of the growth plate was comparable to that of the sham-operated group. Both low and high dose PTH treatments increased the length of the growth plate, and those lengths were comparable to that of the sham-operated group. The fractions of proliferating, maturing and hypertrophic zone in the low dose PTH-treated group were also comparable to those of the sham-operated group. However, high dose PTH treatment slowed down the differentiation of cells from proliferating chondrocytes to maturing and hypertrophic chondrocytes to a greater extent, and therefore the fraction of proliferating chondrocytes of the high dose PTH-treated group was larger than that of the low dose PTH-treated group (73.8 +/- 1.8 Vs 63.3 +/- 1.3%, p < 0.005). From these results, we showed that intermittent PTH treatment could promote linear growth in the ovariectomized growing rat. We propose that PTH may be an alternative drug candidate for promoting linear growth of long bones without the risk for early closure of the growth plate.