Strontium ranelate inhibits wear particle-induced aseptic loosening in mice

The imbalance between bone formation and osteolysis plays a key role in the pathogenesis of aseptic loosening. Strontium ranelate (SR) can promote bone formation and inhibit osteolysis. The aim of this study was to explore the role and mechanism of SR in aseptic loosening induced by wear particles. Twenty wild-type (WT) female C57BL/6j mice and 20 sclerostin-/- female C57BL/6j mice were used in this study. Mice were randomly divided into four groups: WT control group, WT SR group, knockout (KO) control group, and KO SR group. We found that SR enhanced the secretion of osteocalcin (0.72±0.007 in WT control group, 0.98±0.010 in WT SR group, P=0.000), Runx2 (0.34±0.005 in WT control group, 0.47±0.010 in WT SR group, P=0.000), β-catenin (1.04±0.05 in WT control group, 1.22±0.02 in WT SR group, P=0.000), and osteoprotegerin (OPG) (0.59±0.03 in WT control group, 0.90±0.02 in WT SR group, P=0.000). SR significantly decreased the level of receptor activator for nuclear factor-κB ligand (RANKL) (1.78±0.08 in WT control group, 1.37±0.06 in WT SR group, P=0.000) and improved the protein ratio of OPG/RANKL, but these effects were not observed in sclerostin-/- mice. Our findings demonstrated that SR enhanced bone formation and inhibited bone resorption in a wear particle-mediated osteolysis model in wild-type mice, and this effect relied mainly on the down-regulation of sclerostin levels to ameliorate the inhibition of the canonical Wnt pathway.

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Tridax procumbens flavonoids: a prospective bioactive compound increased osteoblast differentiation and trabecular bone formation

BACKGROUND: The Tridax procumbens extracts (TPE) are known for their ethno-medicinal properties to increase osteogenic functioning in mesenchymal stem cells. Recently, we found that the T. procumbens flavonoids (TPF) significantly suppressed the RANKL-induced osteoclasts differentiation and bone resorption. The TPF also promoted osteoblasts differentiation and bone formation demonstrated by increasing bone formation markers in cultured mouse primary osteoblasts. However, the effects of the TPF on in vivo bone formation remain unclear. In this study, we investigated the effects of the TPF on in vivo bone formation, injected the TPF (20 mg/kg) twice a day in the low calcium diet mice and killed them after 21 day. Radiographic and histomorphometric analyses were performed on the dissected bones to determine the anabolic effects of the TPF. RESULTS: Bone mineral density and bone mineral content of the TPF-treated mice were significantly increased compared to the control mice. Bone formation-related indices like osteoblast number, osteoblast surface, bone volume, mineralizing surface, mineral apposition rate and bone formation rate were significantly increased in the TPF-treated mice compared to the control mice. CONCLUSION: Our findings point towards the stimulation of bone formation by TPF, suggested that the TPF could be a potential natural anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Role of Triticum aestivum aqueous extract in glucocorticoid induced osteoporosis in rats.

Administration of aqueous extract of T. aestivum (200 and 400 mg/kg/day, po, for 30 days) and risedronate (20 mg/kg, sc, five times a week for 30 days) following methyl prednisolone sodium succinate (10 mg/kg, sc, thrice a week for 4 weeks) induced osteoporosis in Wistar rats showed an increase in the serum levels of bone mineral content markers, decrease in the serum and urinary levels of bone resorption markers. An incline in strength of femur and tibia was seen particularly with 400 mg/kg of T. aestivum. Maintenance of calcium homeostasis, formation of collagen and scavenging of free radicals can plausibly be the mode of action of aqueous extract of T. aestivum thereby combating osteoporosis induced by glucocorticoids.

Tocotrienol supplementation in postmenopausal osteoporosis: evidence from a laboratory study

OBJECTIVE: Accelerated bone loss that occurs in postmenopausal women has been linked to oxidative stress and increased free radicals. We propose the use of antioxidants to prevent and reverse postmenopausal osteoporosis. This study aimed to examine the effects of tocotrienol, a vitamin E analog, on bone loss due to estrogen deficiency. Our previous study showed that tocotrienol increased the trabecular bone volume and trabecular number in ovariectomized rats. In the current study, we investigated the effects of tocotrienol supplementation on various biochemical parameters in a postmenopausal osteoporosis rat model. MATERIALS AND METHODS: A total of 32 female Wistar rats were randomly divided into four groups. The baseline group was sacrificed at the start of the study, and another group was sham operated. The remaining rats were ovariectomized and either given olive oil as a vehicle or treated with tocotrienol at a dose of 60 mg/kg body weight. After four weeks of treatment, blood was withdrawn for the measurement of interleukin-1 (IL1) and interleukin-6 (IL6) (bone resorbing cytokines), serum osteocalcin (a bone formation marker) and pyridinoline (a bone resorption marker). RESULTS: Tocotrienol supplementation in ovariectomized rats significantly reduced the levels of osteocalcin, IL1 and IL6. However, it did not alter the serum pyridinoline level. CONCLUSION: Tocotrienol prevented osteoporotic bone loss by reducing the high bone turnover rate associated with estrogen deficiency. Therefore, tocotrienol has the potential to be used as an anti-osteoporotic agent in postmenopausal women. .

Utilización de bisfosfonatos en las enfermedades de los huesos / Use of bisphosponates in bone-related diseases

Los bifosfonatos son medicamentos que ayudan a fortalecer los huesos, reducen el riesgo de fracturas y dolor en los que han sido debilitados por el cáncer metastásico. Estos disminuyen la reabsorción ósea de modo general por vía oral; por vía intravenosa se suelen utilizar como tratamiento coadyuvante de algunos tipos de cáncer y, por ende, es necesario tener presente los efectos adversos asociados a su uso. El presente trabajo tiene como objetivo realizar una revisión bibliográfica sobre este grupo de fármacos, los cuales se emplean en el tratamiento de las enfermedades relacionadas con los huesos, para esto se efectuó una búsqueda en la que se utilizaron algunas de las bases de datos disponibles en la web tales como Google, Scirus y Medline durante los últimos 10 años. Se concluye que los bifosfonatos inhiben la reabsorción ósea mediada por osteoclastos y debido a este mecanismo de acción se han empleado en el tratamiento de la osteoporosis

Effects of a Mikania laevigata extract on bone resorption and RANKL expression during experimental periodontitis in rats

OBJECTIVES: The Mikania laevigata extract (MLE) (popularly known in Brazil as "guaco") possesses anti-inflammatory properties. In the present study we tested the effects of MLE in a periodontitis experimental model in rats. We also investigated possible mechanisms underlying such effects. MATERIAL AND METHODS: Periodontal disease was induced by a ligature placed around the mandibular first molars of each animal. Male Wistar rats were divided into 4 groups: non-ligated animals treated with vehicle; non-ligated animals treated with MLE (10 mg/kg, daily); ligature-induced animals treated with vehicle and ligature-induced animals treated with MLE (10 mg/kg, daily). Thirty days after the induction of periodontal disease, the animals were euthanized and mandibles and gingival tissues removed for further analysis. RESULTS: Morphometric analysis of alveolar bone loss demonstrated that MLE-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-κB ligand (RANKL) measured by immunohistochemistry. Moreover, gingival tissues from the MLE-treated group showed decreased neutrophil migration myeloperoxidase (MPO) assay. CONCLUSIONS: These results indicate that MLE may be useful to control bone resorption during progression of experimental periodontitis in rats.

Prospecção de atividade inibitória da pasta de hidróxido de cálcio e acetazolamida sobre Enterococcus faecalis e Candida albicans / Antimicrobial effect of calcium hydroxide paste and acetazolamide against the Enterococcus faecalis and Candida albicans

Introdução: A medicação intracanal é fundamental para o tratamento de um dente avulsionado, sendo a pasta de hidróxido de cálcio comumente indicada. A acetazolamida é uma substância inibidora da anidrase carbônica e da reabsorção óssea, podendo ser sugerida como medicação intracanal em dentes avulsionados. Contudo, para que uma substância seja sugerida, estudos devem comprovar sua eficácia tanto in vitro como in vivo. Objetivo: Avaliar in vitro a ação antimicrobiana da pasta de hidróxido de cálcio e da acetazolamida, associadas a diferentes veículos, contra os micro-organismos Enterococcus faecalis e Candida albicans. Materiais e métodos: As formulações selecionadas foram: acetazolamida (pó) com soro fisiológico; acetazolamida (pó) com glicerina; acetazolamida e hidróxido de cálcio (pó) em porções iguais com soro fisiológico; acetazolamida e hidróxido de cálcio (pó) em porções iguais adicionando-se glicerina; acetazolamida (líquido) e hidróxido de cálcio (pó) com soro fisiológico. Como controle positivo foram utilizadas concentrações de clorexidina de 20%, 10%, 5%, 2,5%, 1,25% e 0,65% e como controle negativo a glicerina. O experimento foi realizado por teste de difusão em ágar. Resultados: Não houve inibição do crescimento das bactérias com os medicamentos utilizados, apenas com o controle positivo.Conclusão: As formulações de hidróxido de cálcio e acetazolamida não apresentaram atividade inibitóriacontra o E. faecalis e C. albicans.

Introduction: The intracanal medication is essential for the treatment of avulsed tooth, being the calcium hydroxide paste usually indicated. The acetazolamide is an inhibiting substance of carbonic anhydrase and the bone resorption, being suggested as intracanal medication in avulsed teeth. However, for this substance became an alternative as intracanal therapeutic agent, it must be tested in vitro and in vivo. Objective: To evaluate, in vitro, the antimicrobial action of calcium hydroxide paste and acetazolamide associated with different vehicles, against the Enterococcus faecalis and Candida albicans. Materials and methods: The experimental groups were: acetazolamide (powder) with physiological serum; acetazolamide (powder) with glycerin; acetazolamide and calcium hydroxide (powder) in equal portions with physiological serum; acetazolamide and calcium hydroxide (powder) in equal portions added with glycerin; acetazolamide (liquid) and calcium hydroxide (powder) with physiological serum. Clorexidine was used for positive control in concentrations of 20%, 10%, 5%, 2.5%, 1.25% and 0.65% and glycerin was used as negative control. The study was carried through by test of diffusion in agar. Results: No experimental groups showed inhibition of the bacterial growth, only inhibited by the positive control. Conclusion: The groups with calcium hydroxide and acetazolamide did not show antimicrobial activity against the E. faecalis and C. albicans.

Bifosfonatos, conexinas y apoptosis de osteoblastos y osteocitos: nuevo mecanismo de acción con implicancias terapéuticas / Bisphosphonates, connexins and apoptosis of osteocytes and osteoblasts: a novel mechanism of action with therapeutic potential

Los bifosfonatos son drogas ampliamente utilizadas para el tratamiento de patologías en las que hay un aumento en la fragilidad ósea. Estos agentes detienen la pérdida de hueso al inhibir la actividad de los osteoclastos, las células que resorben el hueso. Sin embargo, el modesto efecto de los bifosfonatos en el aumento en la masa ósea no explica completamente la disminución en la incidencia de fracturas observada en individuos tratados con estos agentes. Basados en la falta de correlación entre el aumento de la densidad mineral y la disminución en la incidencia de fracturas, hemos explorado la posibilidad de que parte del efecto beneficioso de los bifosfonatos se debe a la inhibición de la apoptosis de los osteocitos. Los osteocitos, osteoblastos diferenciados que se rodean de matriz ósea, constituyen la mayoría de las células que forman el hueso, y, a través de sus prolongaciones, forman una red que recorre el hueso. Debido a su posición en el hueso, los osteocitos constituyen las células ideales para percibir cambios mecánicos u hormonales e iniciar señales que llevan a la reparación del tejido, previniendo el deterioro del hueso y la posibilidad de fracturas. Los osteocitos se comunican entre sí y con las células en la superficie del hueso a través de canales de conexinas (Cx), especialmente Cx43. Nuestro grupo ha demostrado que los bifosfonatos, aún los que carecen de actividad anti-catabólica, previenen la apoptosis de osteocitos in vitro e in vivo. La protección de la viabilidad celular requiere la apertura de hemicanales de Cx43, pero es independiente de la activación de las uniones gap. La apertura de los hemicanales es seguida por la activación de la quinasas Src y ERKs.

Bone quality and osteoporosis therapy / Qualidade óssea e tratamento da osteoporose

Although BMD measured by DXA is a useful clinical tool for osteoporosis diagnosis, changes resulting from osteoporosis treatment only partially explain the observed reduction in fractures. Several other bone properties that influence its resistance to fractures and explain this discrepancy have been defined as "bone quality". Bone quality is determined by its structural and material properties and orchestrated by bone turnover, a continuous process of renewal through which old or damaged bone is replaced by a mechanically healthy bone and calcium homeostasis is maintained. Bone structural properties include its geometry (size and shape) and microarchitecture (trabecular architecture and cortical porosity), while bone material properties include its mineral and collagen composition as well as microdamage and its repair. This review aims to update concepts surrounding bone quality and how drugs employed to treat osteoporosis might influence them.

Embora a DMO, medida por DEXA, seja um recurso clínico útil para o diagnóstico da osteoporose, mudanças resultantes do tratamento da osteoporose explicam apenas parcialmente a redução de fraturas. As demais propriedades ósseas que influenciam sua resistência a fraturas, que não se referem à massa óssea e explicam a discrepância entre os valores de DMO e o risco de fratura, têm sido definidas como "qualidade óssea". A qualidade óssea é determinada por suas propriedades estruturais e materiais e orquestrada pela remodelação óssea, um processo contínuo de renovação por meio do qual o osso velho ou danificado é substituído por um osso mecanicamente saudável e a homeostase do cálcio é mantida. As propriedades estruturais ósseas incluem suas geometria (tamanho e formato) e microarquitetura (arquitetura trabecular e porosidade cortical), enquanto as propriedades materiais referem-se à sua composição mineral e colágena assim como ao microdano e seu reparo. O objetivo desta revisão é uma atualização sobre qualidade óssea e como os medicamentos empregados no tratamento da osteoporose podem modificá-la.

Osteonecrosis de los maxilares inducida por el uso de bifosfonatos: prevención y pautas de tratamiento / Osteonecrosis of the jaws associated with biphosphonates: prevention and treatment

La osteonecrosis de los maxilares relacionada con los bifosfonatos (ONMB) es una enfermedad que puede afectar la calidad de vida y provocar significativa morbilidad a los pacientes. Los bifosfonatos son drogas que se utilizan para el tratamiento de osteoporosis, osteopenia, metástasis ósea, mieloma múltiple, enfermedad de Paget, etc. Esta complicación puede aparecer usualmente después de una simple cirugía dentoalveolar. La patogénesis estaría relacionada con la inhibición de la función de los osteoclastos y de la remodelación ósea. El objetivo de nuestro trabajo es informar a odontólogos, pacientes y partes interesadas sobre el riesgo del uso de los bifosfonatos, así comotambién sobre la prevención, estadificación y pautas de tratamiento de la ONMB basados en la conducta de trabajo actual de la Asociación Americana de Cirugía Oral y maxillofacial (AAOMS). Asimismo se presentan 2 casos clínicos y su resolución.

Triiodothyronine (T3) does not induce Rankl expression in rat Ros 17/2.8 cells

Osteoclastogenesis may be regulated via activation of the RANK/RANKL (receptor activator of nuclear factor-kappa B/ receptor activator of nuclear factor-kappa B ligand) system, which is mediated by osteoblasts. However, the bone loss mechanism induced by T3 (triiodothyronine) is still controversial. In this study, osteoblastic lineage rat cells (ROS 17/2.8) were treated with T3 (10-8 M, 10-9 M, and 10-10 M), and RANKL mRNA (messenger RNA) expression was measured by semiquantitative RT-PCR. Our results show that T3 concentrations used did not significantly enhance RANKL expression compared to controls without hormone treatment. This data suggests that other mechanisms, unrelated to the RANK/RANKL system, might be to activate osteoclast differentiation in these cells.

A osteoclastogênese pode ser regulada via ativação do sistema RANK/RANKL (receptor ativador do fator nuclear kapa B/ ligante do receptor do fator nuclear kapa B), que é mediado pelos osteoblastos. Entretanto, o mecanismo de perda óssea induzido pelo T3 (triiodotironina) ainda é controverso. Neste estudo, a linhagem osteoblástica de células de rato ROS 17/2.8 foi tratada com T3 (10-8 M, 10-9 M e 10-10 M), e a expressão do mRNA do RANKL foi medida por RT-PCR semiquantitativo. Nossos resultados mostraram que as concentrações de T3 utilizadas não induziram significativamente a expressão do RANKL, comparado ao controle (sem tratamento hormonal). Estes dados sugerem que outros mecanismos, não relacionados ao sistema RANK/RANKL, são usados para ativar a diferenciação osteoclástica nestas células.

O gálio e a patologia óssea / Gallium and bone pathology

PROPOSTA: Revisão de trabalhos científicos referentes à incorporação do gálio no tecido ósseo, ao mecanismo da atividade terapêutica desse elemento, bem como a formação, crescimento e solubilidade da hidroxiapatita na presença dos sais de gálio. JUSTIFICATIVA: Diferente de outras drogas que impedem a perda de cálcio, os sais de elemento traço gálio são eficazes em hipercalcemia severa. O gálio (geralmente na forma de nitrato) aumenta a concentração de cálcio e fósforo no osso, influindo nos osteoclastos de maneira direta não tóxica, em doses surpreendentemente baixas. Apesar de que os detalhes do mecanismo de ação do gálio não são bem esclarecidos, está comprovado que esse mecanismo envolve a inserção do gálio na matriz de hidroxiapatita, protegendo-a contra a reabsorção e melhorando as propriedades biomecânicas do sistema esquelético. Este fármaco age também nos componentes celulares do osso, impedindo sua absorção ao diminuir a secreção ácida dos osteoclastos. São necessárias mais publicações sobre o uso do gálio no tratamento de várias doenças onde prevalece esta patologia. CONCLUSÕES: Devido as suas características interessantes e promissoras, o gálio merece ser futuramente avaliado do ponto de vista experimental e clínico, como um agente antiabsortivo em ortopedia, traumatologia e doenças relacionadas com o câncer. Maior conhecimento dos mecanismos envolvidos pode fornecer as idéias para estratégia terapêutica, com o objetivo de diminuir hipercalcemia e perda óssea. Espera-se que novos compostos do gálio sejam desenvolvidos e avaliados clinicamente.

PURPOSE: To review the literature concerning the incorporation of gallium into bone tissue, mechanisms of therapeutic activity of this element, as well as the formation, growth and solubility of hydroxiapatite in the presence of gallium salts. JUSTIFICATION: In contrast to other calcium-saving drugs, salts of trace element gallium are effective in severe hypercalcemias. Gallium (most commonly in the form of its nitrate) enhances calcium and phosphorus content of the bone and has direct, noncytotoxic effects on osteoclasts at markedly low doses. Although the details of gallium action on the bone are still uncertain, it is well established that the mechanism involves gallium insertion into the hydroxiapatite matrix protecting it from resorbtion and improving biomechanical properties of the skeletal system. The drug also acts on the cellular components of bone to reduce bone resorbtion by decreasing acid secretion by osteoclasts. More has to be published about the use of gallium in managing a series of clinical conditions in which this pathology is pronounced. CONCLUSIONS: Due to its interesting and promising profile gallium merits further experimental and clinical evaluation as an antiresorbtive agent in orthopaedics, traumatology and cancer-related conditions. Greater knowledge of the mechanisms involved may provide insights for therapeutic strategies aimed at diminishing hypercalcemy and bone loss. New gallium compounds are expected to be developed and tested clinically.

Uso de bifosfonatos em crianças e adolescenes / Use of bisphophonates in children and adolescents

Os bifofonatos são os medicamentos mais amplamente utilizados no tratamento de doenças associadas ao aumento de reabsorção óssea em adulto, incluindo a osteoporose pós-menopausa (indicação mais frequente), a doença de Paget e metástases ósseas. Os bifofonatos têm sido usados com bons resultados em crianças e pouco ou nenhum efeito colateral em várias doenças: osteogênese imperfeita, osteoporose induzida por corticóide, idiopática juvenil e por desuso, doença óssea metabólica, calcificação heterotópica de tecidoas moles, hipercalcemia resistente, hipervitaminose D e displasia fibrosa (DF) da síndrome de Mc-Cune Albright (SMA). Os melhores resultados são descritos nas crianças portadoras de osteogênese imperfeita, DFO da SMA e osteoporose induzida por corticóides. Os bifofonatos são análogos sintéticos estáveis no pirofosfato que inibem o crescimento e a dissolução dos cristais de hidroxiapatita do osso a partir da redução da atividade osteoclástica. Nos tecidos, promovem supressão do turnover ósseo, evidenciada no exame histológico e histomorfométrico. Durante seu uso ocorre aumento da densidade óssea devido à diminuição da taxa de iniciação de novos ciclos de remodelagem e consequente redução dos espaços de remodelamento ósseo. Emboram existam questionamentos sobre possíveis efeitos adversos no esqueleto em crescimento e na qualidade do osso formado a longo prazo, os bons resultados descritos são encorajadores e os efeitos colaterais bem tolerados.

Osteonecrosis de los maxilares asociada al uso de bifosfonatos: rol del odontólogo / Biphosphonate-associated osteonecrosis of the jaws: the dentist´s role

Los bifosfonatos son fármacos inhibidores de la reabsorción ósea, utilizados en el tratamiento de aquellas afecciones caracterizadas por una densidad ósea disminuida o por un gran recambio óseo. La osteonecrosis de los maxilares (ONJ) corresponde a una complicación potencial y severa derivada del uso de los aminofosfonatos que se traduce en la aparición de hueso expuesto y necrótico por aparente colapso vascular. Los huesos más afectados del organismo con los maxilares, se cree que por diversas razones: a) por la presencia de dientes y ligamento periodontal, lo que generaría un remodelado óseo continuo y la posible conexión con el medio externo, b) una mucosa muy delgada sometida al estrés masticatorio y c) la gran irrigación que poseen estos huesos que favorecería una mayor biodisponibilidad del medicamento. En esta revisión se describen las características clínicas y radiográficas de la ONJ, su distribución y prevalencia en la población, los medicamentos más importantes relacionados a esa patología, principalmente aquellos de última generación que incorporan en una de sus cadenas una base nitrogenada (amino-bifosfonatos), y se analizó el rol que el odontólogo debe jugar en estos pacientes antes, durante y después del tratamiento.

Tratamento da doença de Paget óssea: importância do ácido zoledrônico / Treatment of Paget's disease of bone: importance of the zoledronic acid / Treatment of Paget's disease of bone: importance of the zoledronic acid

A doença de Paget é uma doença esquelética, de distribuição monostótica ou poliostótica, podendo ser causada por uma infecção viral e/ou fatores genéticos. É caracterizada por um aumento da remodelação óssea, resultando em anormalidade da arquitetura óssea. A excessiva reabsorção óssea osteoclástica, seguida secundariamente de aumento da atividade osteoblástica, leva à substituição do osso normal por osso desorganizado, aumentado, e com estrutura enfraquecida, propensa a deformidades e fraturas. A doença de Paget pode ser diagnosticada através de exames radiológicos, cintilografia e exames bioquímicos. O objetivo primário do tratamento é reduzir a dor e o risco do aparecimento das complicações a longo prazo. Atualmente dispõe-se de drogas anti-reabsortivas potentes, as quais controlam a reabsorção óssea e proporcionam uma grande melhora no tratamento. O ácido zoledrônico, um bisfosfonato de última geração, tem a vantagem de maior potência e remissão mais prolongada, além de um tempo de infusão curto.

Paget's disease is a localised monostotic or polyostotic bone disease of unknown origin. It may be caused by a slow viral infection and/or genetic factors. It is characterised by increased bone remodelling and an initially excessive osteoclastic bone resorption, followed by a secondary increase in osteoblastic activity, leading to replacement of the normal bone by a disorganized, enlarged, and weakened osseous structure prone to deformities and fractures. The disease may be diagnosed by radiography, scintigraphy and biochemical tests. The primary aim of treatment is to reduce pain and risk of developing long-term complications. Potent antiresorptive drugs are now available, which control the increased bone remodelling and have led to a dramatic improvement in treatment. Zoledronic acid, a new generation of bisphosphonates, has the advantage of great potency and long duration of remission and a short infusion time.

Bisphosphonates / Bisfosfonatos

Osteoporosis is the result of bone loss due to an imbalance in bone turnover such that bone resorption exceeds bone formation. Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. In clinical studies, several bisphosphonates prevent bone loss, preserve bone structure, improve bone strength and, in patients with osteoporosis, substantially reduce fracture risk. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men and drug-induced bone loss. Intermittent oral dosing and intravenous administration are more convenient than the original daily dosing regimen. These drugs are generally well tolerated and have an excellent safety profile in that serious side effects are uncommon. Potent bisphosphonates are generally the preferred treatment option for most patients with or at risk for osteoporosis.

Osteoporose é o resultado da perda óssea devida a um imbalanço no turnover ósseo, onde a reabsorção óssea excede sua formação. Os bisfosfonatos são inibidores potentes da atividade osteoclástica, que reduzem o turnover ósseo e restabelecem o balanço entre a reabsorção e a formação óssea. Em estudos clínicos, vários bisfosfonatos previnem a perda óssea, preservam sua estrutura, melhoram sua força e substancialmente reduzem o risco de fraturas em pacientes com osteoporose. Eles são efetivos em várias situações clínicas, incluindo a osteoporose pós-menopáusica, a reduzida massa óssea em homens e perda óssea induzida por drogas. Doses orais intermitentes e administração intravenosa são mais convenientes do que o esquema original de doses diárias. Essas drogas são geralmente bem toleradas e têm um excelente perfil de segurança, no qual efeitos colaterais sérios são incomuns. Os bisfosfonatos potentes são geralmente a opção terapêutica preferida para a maioria dos pacientes com ou em risco de osteoporose.

Monitoring of Risedronate by biochemical bone markers in clinical practice.

The study of trend of Risedronate 10 mg/day in menopausal women with a high level of resorptive bone marker (Betacrosslaps, CTx) by the following bone markers:Bone alkaline phosphatase (formation marker) total alkaline phosphatase (TAlP), NMID osteocalcin, undercarboxylated osteocalcin (UcOC) and procollagen type 1 carboxyl propeptides (PICP). Risedronate does not suppress bone resorption deeply that enhances the bone recovers quickly after withdrawal. The level of undercarboxylated osteocalcin was increased after one year of treatment; it may be a sign of vitamin K2 deficiency. The bone alkaline phosphatase was decreased at the end of 12 months and Procollagen type 1 carboxyl propeptides (PICP) of twelfth month changed significantly compared to the sixth months of treatment (p=0.001) The once week 70 mg/week group also changed of CTx the same as daily dose group.

Recomendaciones para el manejo de la osteoporosis

En la actualidad la osteoporosis se considera solamente como un riesgo de fractura y por lo tanto se debe analizar en compañía de otros riesgos para decidir la conveniencia del tratamiento. Es más importante considerar la calidad ósea que confiere la resistencia, en la que la densidad ósea es uno de los varios componentes junto con la microarquitectura, la matriz y el recambio óseo. El tratamiento de la osteoporosis se hace en forma individual, considerando la edad y el antecedente de fractura, para así seleccionar varios recursos que se pueden agrupar en antiresortivos y anabólicos. Entre los primeros están los estrógenos, los bisfosfonatos y los moduladores selectivos del receptor de estrógenos como los principales; los anabólicos aún se encuentran en estudio y el más adelantado es la parathormona sintética. La administración de calcio y vitamina D no es suficiente para el tratamiento de la osteoporosis. El principal problema del tratamiento, que ha provocado una baja adherencia es el costo de los medicamentos y la falta de información sobre la necesidad de que el tratamiento sea a muy largo plazo.

Osteoporosis has to be considered only as a risk factor for bone fractures and its measurement by the bone mass index has some limitations. The aim of treatment of osteoporosis is to reduce the frequency of fractures (especially at the vertebral and the hip) which are responsible for morbidity and mortality with the osteoporosis. It has been demonstrated that antiresorptive drugs (bisphosphonates, estrogens, raloxifen) as well as anabolic agents (synthetic parathormone) are useful for preventing fractures. Calcium and vitamin D supplementation is not sufficient to treat persons with osteoporosis. Choice of treatment depends of age, the presence or absence of prevalent fractures, and the degree of bone mineral density measured at the spine and hip. The main inconvenient for the adherence of treatment is the high cost of the medicaments and agents as well as the poor information given to the patients.