Analysis of the Degree of Information of Dental Surgeons about Antiresorptive Drugs According to the Time Since Graduation in Dentistry

ABSTRACT Objective: To determine the level of scientific information of dental surgeons who carry out their professional activities in Brazil about antiresorptive drugs and indicated pharmacological procedures aiming at the prevention of osteonecrosis of the jaws and the therapy of drug sequelae that may occur, considering the time since graduation in Dentistry. Material and Methods: This is a quantitative cross-sectional study in which 339 dentists were consulted using the virtual questionnaire containing topics of personal nature, elements contained in the anamnesis carried out and knowledge about antiresorptive drugs, including indications, adverse effects and treatments applied. Chi-square and Fisher's exact tests were performed to analyze associations of data described by absolute and relative frequencies with professionals' time since graduation. All analyses were performed using the R software, with a 5% significance level. Results: Those who revealed to have graduated for more than five years with the highest academic degree were those who demonstrated maximum knowledge of antiresorptive drugs or revealed that, somehow, they had information about them (p<0.05). Conclusion: Dental surgeons in Brazil who have more than five years since graduation have more scientific information about antiresorptive drugs and pharmacological procedures, which can positively contribute to the prevention of osteonecrosis of the jaws and treatment of drug sequelae that may occur.

Avaliação da resposta óssea de uma superfície de implante revestida com odanacatib em ratas ovariectomizadas: estudo experimental in vivo / Evaluation of the bone response of an odanacatib coated implant surface in ovariectomized rats: in vivo experimental study

Atualmente novos princípios ativos de função reabsortiva têm ganhado campo de estudo para avaliar seus mecanismos e comportamento biológico. Com isso, um novo antirreabsortivo, inibidor da catepsina K tem apresentado efeito positivo na osseointegração. Este estudo tem como objetivo avaliar a resposta óssea da superfície de implantes revestida por duplo ataque ácido e Odanacatib (MK-0822) em ratas ovariectomizadas. Neste estudo foram utilizadas ratas (Albinus, Wistar) ovariectomizadas ou sham (placebo). Cinquenta e dois (52) tiveram as superfícies revestidas por duplo ataque ácido e MK-0822 a 0,06 mg/ml através do método biomimético, e 48 implantes foram instalados em tíbias de ratas ovariectomizadas ou sham. Microscopia eletrônica de varredura (MEV) e energia dispersiva de raios-x (EDS) foram realizadas em 4 implantes após tratamento de superfície, para análise da topografia e composição química, além da realização da análise do ângulo de contato em 16 discos de titânio comercialmente puro tratados com as mesmas superfícies. Aos 15 e 40 dias após instalação de implantes (n=6), foi realizada microtomografia computadorizada. Dados quantitativos foram avaliados adotando-se o nível de significância p< 0,05. Além dos resultados topográficos favoráveis para os grupos tratados com MK-0822, os resultados microtomográficos apresentaram diferença estatisticamente significante entre os grupos SHAM e OVX na maioria dos parâmetros (p< 0,05). Ainda assim, os grupos tratados com MK-0822 apresentaram resultado semelhante ou maior, porém sem diferença estatística, em relação ao grupo controle em todos os parâmetros (TV, BV, BV ̸TV, Tb.Sp e Tb.N)(AU)

Currently new active principles of resorptive function have gained field of study to evaluate their mechanisms and biological behavior. Thereby a new anti-absorbent, cathepsin K inhibitor has had a positive effect on osseointegration. This study aims to evaluate the bone response of the surface of implants coated by double acid-etched and Odanacatib (MK-0822) in ovariectomized rats. In this study, either ovariectomized rats (Albinus, Wistar) or sham (placebo) have been used. Fifty-two (52) implants had the surfaces coated with double acid-etched and MK-0822 at 0,06 mg/ml by the biomimetic method and 48 implants were installed on sham or ovariectomized rat tibias. Scanning electron microscopy (SEM) and X-ray dispersive energy (EDS) were performed in 4 implants after surface treatment for analysis of topography and chemical composition, in addition to performing contact angle analysis on 16 commercially pure titanium discs treated with the same surfaces. At 15 and 40 days after implant installation, microcomputer tomography was performed. Quantitative data was evaluated by adopting the significance level of p< 0.05. Besides the favorable topographic results to MK-0822 coated implants group, the microtomographic results presents statistically significant differences between the SHAM and OVX groups at most of the parameters (p< 0,05). Nevertheless, the MK-0822 coated group presents similar or higher values, although without statistic differences related to the control group in all parameters (TV, BV, BV ̸TV, Tb.Sp and Tb.N)(AU)

A systematic review assessing occurrence of medication-related osteonecrosis of the jaw following dental procedures

Aim: This study aimed to systematically review existing literature regarding the association between dental procedures­such as tooth extractions and periodontal therapy­and occurrence of medication-related osteonecrosis of the jaw (MRONJ) in individuals using bone-modifying drugs. Methods: Search strategies were performed in PubMed, Scopus, Web of Science and Cochrane Library for a timeframe ending in December 2021. Study selection, data extraction and risk of bias were analyzed independently by two researchers. Three meta-analyses were performed, estimating the crude risk ratio (RR), the adjusted odds ratio (OR) and the adjusted hazard ratio (HR) for the association between tooth extraction and MRONJ. Results: Of the 1,654 studies initially retrieved, 17 were ultimately included. The majority of patients with MRONJ in these studies were female, with a mean age of 64 years. Zoledronic acid was the most commonly used drug among patients with MRONJ, and cancer was the most frequent underlying health condition. Regarding the performed meta-analyses, crude and adjusted analyses demonstrated that tooth extraction increased the risk for MRONJ by 4.28 (95% confidence interval [95%CI]: 1.73­10.58), the OR for MRONJ by 26.94 (95%CI: 4.17­174.17), and the HR for MRONJ by 9.96 (95%CI: 4.04­24.55). Conclusion: It was concluded that performing dental procedures, especially tooth extraction, in patients using bone-modifying drugs increased the risk of MRONJ occurrence and, therefore, should be avoided. Further studies, using adjusted data, are warranted

Clinical and demographic characterization of the population with osteoporosis in two reference medical centres in Colombia / Caracterización clínica y demográfica de la población con osteoporosis en 2 centros médicos de referencia en Colombia

ABSTRACT Introduction: Osteoporosis is a public health problem. However, there is still a lack of data in Colombia on the characteristics of patients with osteoporosis. Objectives: This study aims to characterize the population with osteoporosis without previous diagnosis. Materials and methods: Observational, retrospective, descriptive study in patients with osteoporosis. Patients diagnosed between 2014 and 2017 were included. The information was obtained from the patient medical records and the densitometry results. Results: Most (92.2%) of the patients came from Medellín, and the rest from Cali. The mean age of the population was 65.1 years (SD: 9.97). As regards the history of fracture, it was reported that 12.0% had suffered from vertebral fractures, 2.3% had a history of fracture in the distal radius, 2.8% in the femoral neck, and 1.4% had had femoral shaft fracture. Bone densitometry showed a mean T-score of -2.90 in the femoral neck; -3.02 in total hip; -3.03 in the lumbar spine, and -3.42 in the 33% radius. In the 602 patients who had a control bone densitometry, an average BMD gain was seen in all the evaluated regions. Conclusions: The present study has enabled the characterizing of patients from 2 Colombian cities with a diagnosis of osteoporosis. The 2 most frequently reported locations for the diagnosis of osteoporosis were lumbar spine and femoral neck. An average BMD gain was also observed.

RESUMEN Introducción: La osteoporosis es un problema de salud pública, sin embargo, en Colombia en la actualidad faltan datos sobre las características de los pacientes con esta enfermedad. Objetivos: Este estudio pretende caracterizar la población con osteoporosis sin diagnóstico previo. Materiales y métodos: Estudio observacional, retrospectivo, descriptivo en pacientes con osteoporosis. Incluyó a pacientes diagnosticados entre el 2014 y el 2017. La información fue obtenida a partir de las historias clínicas de los pacientes y el resultado de la densitometría. Resultados: El 92,2% de los pacientes provenía de Medellín y los restantes de Cali. La edad promedio ± desviación estándar de la población fue 65,1 ± 9,97 arios. En cuanto al antecedente de fractura, se reportó que el 12,0% había presentado fracturas vertebrales, el 2,3% tenía antecedente de fractura en radio distal, el 2,8% en cuello femoral y el 1,4% había tenido fractura de diáfisis femoral. La densitometría ósea (DMO) mostró un T-score promedio de -2,90 en cuello femoral, -3,02 en cadera total, -3,03 en columna lumbar y-3,42 en radio 33%. En los 602 pacientes que contaban con DMO de control se vio una ganancia de la DMO promedio en todas las regiones evaluadas. Conclusiones: El presente estudio permitió caracterizar a pacientes con diagnóstico de osteoporosis en 2 ciudades de Colombia. Las 2 localizaciones más reportadas para el diagnóstico de osteoporosis fueron columna lumbar y cuello femoral; adicionalmente, se observó una ganancia de la DMO promedio.

Impact of Antiresorptive Agents on Maxillary Bones: a Narrative Literature Review / Impacto dos Agentes Antirreabsortivos nos Ossos Maxilares: uma Revisão de Literatura narrativa

Abstract Antiresorptive drugs operate in the bone metabolism modulation and are widely used in the treatment of bone metastases and bone losses related to hormonal deficiency. Although this therapy shows satisfactory results, there are adverse effects associated with its use, such as osteonecrosis of the jaws. Medication-related osteonecrosis of the jaws (MRONJ) is, therefore, a serious and challenging condition with important implications in dentistry. The aim was to conduct a narrative literature review on anti-resorptive drugs and their latest repercussions on the maxillary bones. The review was carried out through a bibliographic search using Decs/Mesh descriptors of interest, in Portuguese and English, in the PubMed, Virtual Health Library (VHL) and Scielo databases. After applying the inclusion and exclusion criteria, a total of 33 studies were selected for analysis. It can be noticed that therapy with anti-resorptive agents is complex, especially in dental practice, since MRONJ is a complication that is difficult to manage. Regarding the therapeutic options, these are divided into conservative, surgical or adjuvant therapy, however, there are no protocols in the literature, and there is no consistency regarding the indication of the suspension of the drug administration - "Drug Holiday". Thus, it is important that the multidisciplinary team seeks strategies that minimize complications and promote control over the use of these drugs. In addition, there is a need for investigations that contribute with guidelines for the management and control of adverse effects resulting from therapy with antiresorptive drugs. (AU)

Resumo As drogas antirreabsortivas atuam na modulação do metabolismo ósseo e são indicadas para o tratamento de metástases ósseas e perdas ósseas relacionadas à deficiência hormonal. Ainda que esta terapia apresente resultados satisfatórios, observam-se efeitos adversos associados ao seu uso, como a osteonecrose dos maxilares. A osteonecrose dos maxilares associada ao uso de medicamentos (OMAM) é, portanto, uma condição séria e desafiadora com implicações importantes na Odontologia. O objetivo foi realizar uma revisão narrativa de literatura sobre as drogas antirreabsortivas e suas respectivas repercussões nos ossos maxilares. A revisão foi realizada através de busca bibliográfica utilizando descritores Decs/Mesh de interesse, em português e inglês, nas bases de dados PubMed, Biblioteca Virtual de Saúde (BVS) e Scielo. Após aplicação dos critérios de inclusão e exclusão, um total de 33 trabalhos foram selecionados para análise. Pode-se constatar que a terapia com agentes antirreabsortivos é complexa, sobretudo na prática odontológica, visto que a OMAM é uma complicação de difícil manejo. Em relação às condutas terapêuticas para esta condição, divide-se em terapia conservadora, cirúrgica ou adjuvante, todavia, não existem protocolos validados na literatura, bem como não há consistência quanto à indicação do intervalo de suspensão da administração da droga - "Drug Holiday". Desse modo, é importante que a equipe multidisciplinar busque estratégias que minimizem as complicações e promovam o controle no uso dessas drogas. Além disso, nota-se a necessidade de realizar investigações que contribuam com diretrizes para o manejo e controle dos efeitos adversos decorrentes da terapia com medicamentos antirreabsortivos. (AU)

Osteonecrosis de los maxilares asociada a medicamentos: revisión de la literatura y propuesta para la prevención y manejo / Osteonecrosis of the jaws

Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region. It has been associated with the use Biphosphonates and denosumab for osteoporosis. Although its etiology is unclear, it may be related to a decrease in bone turnover produced by these drugs, rendering the bone more prone to generate cell necrosis during invasive dental procedures, especially in the posterior region of the jaw. There is no consensus about the prevention and treatment of this condition. The aim of this paper is to present a review of the literature with the main characteristics of osteonecrosis of the jaws associated with drugs, together with a proposal for prevention and treatment for these patients.

Avaliação do efeito do tratamento com alendronato na artrodese lombar em ratas osteoporóticas / Evaluation of alendronate treatment on lumbar arthrodesis in osteoporotic rats

A osteoporose é um distúrbio osteometabólico caracterizado pela redução da densidade mineral óssea. Estima-se que 200 milhões de pessoas possuam osteoporose no mundo. A doença é fator de risco para falha do processo de fusão vertebral, que consiste na consolidação de vértebras adjacentes através da colocação de enxertia óssea e estabilização mecânica, fundamental para o sucesso das cirurgias da coluna vertebral. O alendronato é um medicamento antirreabsortivo utilizado no tratamento da osteoporose. Apesar de sua eficácia, sugere-se que retarda o processo de remodelamento no sítio cirúrgico da fusão vertebral, atrasando a osteointegração do enxerto aos corpos vertebrais. Ainda não há consenso sobre a melhor abordagem medicamentosa para os pacientes osteoporóticos que se encontram em uso crônico de alendronato e que serão submetidos ao procedimento cirúrgico de fusão vertebral. Este estudo avaliou o efeito do alendronato na consolidação óssea do procedimento de fusão vertebral em ratas osteoporóticas. Quinze ratas da linhagem Sprague Dawley foram divididas em três grupos: Grupo Não-OVX (n=3) - ratas não submetidas a ooforectomia e submetidas a fusão espinhal; Grupo OVX (n=5) - ratas submetidas a ooforectomia entre 8 a 12 semanas de vida e à fusão vertebral 12 semanas após a ooforectomia e Grupo ALN (n=7) - ratas ooforectomizadas e submetidas a fusão vertebral que receberam semanalmente 70µg/kg de alendronato iniciado 5 semanas antes da fusão vertebral e mantido até a eutanásia. Foram coletadas amostras de sangue semanalmente e os animais foram submetidos a eutanásia 8 semanas após a fusão vertebral. A condição osteoporótica foi confirmada através da dosagem por ELISA dos níveis plasmáticos de CTX-I 12 semanas após ooforectomia, que foi maior no grupo OVX em relação ao grupo Não-OVX (p=0,0086). Os parâmetros da microestrutura do corpo vertebral medidos através da microtomografia computadorizada (µCT) denotam redução na fração de volume ósseo (BV/TV) (p=0,116), no número de trabéculas (Tb.N) (p=0,116), na espessura das trabéculas (Tb.Th) (p=0,033), e leve aumento na desconexão entre as trabéculas (Tb.pf p = 0,086). Quanto à eficiência da fusão, a avaliação radiográfica do segmento lombar revelou taxa de fusão de 75% (3/4) no grupo Não-OVX, 100% (3/3) no grupo OVX e nenhuma fusão no grupo ALN. Pela avaliação manual, os resultados foram semelhantes para os grupos Não-OVX e OVX e de 57,1% (4/7) no grupo ALN. A avaliação dos aspectos estruturais da massa da fusão por µCT revelou maior BV/TV (p ≤ 0,05), maior Tb.N (p ≤ 0,01), maior espaçamento entre as trabéculas (Tb.Sp) (p ≤ 0,01) e Conn.Den (p = 0,02) no grupo ALN em relação aos grupos OVX e não OVX. O grupo ALN também apresentou maior Tb.Th (p = 0,04) e menor Tb.pf (p = 0,03) do que o grupo OVX. As ratas osteoporóticas submetidas a cirurgia de fusão vertebral e tratadas com alendronato apresentaram menor taxa de fusão vertebral, apesar de possuir melhor qualidade da massa de fusão. Imaginavamos que o tratamento crônico com alendronato, assim como o tratamento iniciado após a cirurgia, leve à formação de massas de fusão com maior qualidade trabecular e mais exuberantes, porém, diferente do observado quando o tratamento é iniciado após a cirurgia, não resulta em aumento na taxa de fusão

Osteoporosis is an osteometabolic disorder characterized by reduced bone mineral density. About 200 million people are affected in the world and the disease is a risk factor for pseudoarthrosis in spinal fusion. Alendronate is a bisphosphonate medication that inhibits bone resorption and is used to treat osteoporosis. Despite its effectiveness, it is suggested that`s impairs bone remodeling at the surgical site of spinal fusion, delaying the osteointegration of the bone graft to the vertebral bodies. There is still no consensus on the best approach for osteoporotic patients who are in chronic use of alendronate and who will undergo surgical procedure for spinal fusion. This study sought to examine the effect of the chronic use of alendronate on bone formation of spinal fusion in osteoporotic rats. Fifteen Sprague Dawley adult female rats were divided into three groups: Non-OVX (n=3) ­ non-ovariectomized rats submitted to posterolateral lumbar spinal fusion; OVX (n=5) - rats submitted to ovariectomy at 8 ­ 12 weeks of age and to posterolateral lumbar spinal fusion 12 weeks later; and ALN (n = 7) ­ ovariectomized rats submitted to spinal fusion in which weekly subcutaneous injections of Alendronate (70µg/kg) were administered from 5 weeks before the spinal fusion until euthanasia. Blood samples were collected weekly and euthanasia was performed 8 weeks after the spinal fusion procedure. Development of osteoporosis was evaluated through the plasmatic dosage of CTX-I, in which we observed a significant increase in the OVX group (p=0.0086). Bone loss was confirmed by micro-CT analysis of the fourth lumbar vertebra, with slightly reduction in the bone volume (BV/TV) (p=0.116), trabecular number (Tb.N) (p=0.116), significantly reduction in the trabecular tickness (Tb.Th) (p=0.033), and slightly increase in the trabecular bone pattern factor (TB.pf) (p = 0.086). Radiographic evaluation of the lumbar spine revealed fusion rate of 75% (3/4) in Non-OVX, 100% (3/3) in OVX, and no fusion in ALN. According to manual palpation, we observed similar results for the non-OVX and OVX goup, while in the ALN group we observed 57.1% (4/7) of fusion rate. New bone formation identified on µCT imaging of bilaterally fused specimens demonstrated a higher BV/TV (p ≤ 0.05), Tb.N (p ≤ 0.01), Tb.Sp (p ≤ 0.01), and connective density (Conn.Den, p = 0.02) in ALN than in nonOVX and OVX groups. The alendronate also improved the Tb.Th (p = 0.04) and Tb.pf (p = 0.03) in comparisson to OVX group. This study demonstrates that, despite the better quality of new bone formation after long term administration of alendronte in osteoporotic rats submitted to posterolateral spinal fusion, the treatment does not improve the fusion rates

Biomateriais de substituição óssea para procedimentos de reconstrução alveolar em implantodontia / Bone replacement biomaterials for alveolar reconstruction procedures in implantology

Introdução: a reconstrução do processo alveolar para a reabilitação de pacientes edêntulos com implantes dentários vem se tornando uma realidade segura e previsível. Desta forma, conhecer as características destes tecidos e biomateriais é fundamental para o sucesso. Contudo, a diversidade de marcas e produtos presentes no mercado geram dúvidas na seleção do biomaterial. Objetivo: este estudo tem como objetivo caracterizar os biomateriais disponíveis no mercado brasileiro para procedimentos de reconstrução óssea em implantodontia. Metodologia: Foram incluídos 18 biomateriais de substituição óssea disponíveis no mercado nacional (Brasil), registrados e regulamentados pela agência nacional de vigilância sanitária (ANVISA). As empresas fabricantes foram contatadas para fornecer as informações dos seus respectivos produtos. Resultados: Após a análise dos 18 biomateriais encontrados no mercado nacional, as informações obtidas segundo os fabricantes foram classificadas nos seguintes itens: produto e empresa, granulometria, porosidade, forma de apresentação, composição, origem, propriedade biológica e se for fe procedência nacional ou importado. Discussão: conforme as propriedades de cada tecido ou material, ele pode possuir um ou mais mecanismos de formação óssea. A composição química, forma física e as diferenças de superfície resultam em diferentes níveis de reabsorção. Dessa forma, é importante para o clínico conhecer a natureza variada dos biomateriais disponíveis que vão determinar a velocidade e sua forma de reabsorção. Conclusão: Este estudo tabulou os biomateriais estudados, quanto suas principais características biológicas, visando orientar os profissionais da saúde na escolha do biomaterial mais adequado para alcançar seus objetivos no tratamento

Concordancia de la utilización de teriparatide o ácido zoledrónico en pacientes con osteoporosis con recomendaciones internacionales, en una empresa de salud de Colombia / Concordance in the use of teriparatide or zoledronic acid in patients with osteoporosis with international recommendations, in a health company of Colombia

RESUMEN Introducción: Los bifosfonatos son la primera línea de tratamiento para la osteoporosis; siendo el zolendronato el más efectivo. La teriparatide (agente anabólico), dado su alto costo, debería restringirse al tratamiento de pacientes más afectados y luego de un adecuado tratamiento con bifosfonatos. Objetivo: Establecer el porcentaje de pacientes con osteoporosis, en tratamiento con teriparatide o ácido zoledrónico en Colombia, que se ajusta a recomendaciones de organizaciones internacionales. Método: Estudio de utilización de medicamentos retrospectivo, enero 2012-diciembre 2015, en pacientes con osteoporosis y en tratamiento con teriparatide o ácido zoledrónico. Se revisó información sociodemográfica y clínica, y el grado de concordancia del uso de teriparatide o ácido zoledrónico con recomendaciones de tres guías clínicas internacionales: National Osteoporosis Foundation, National Institute for Health and Clinical Excellence y Scottish Intercollegiate Guidelines Network. Resultados: Se incluyeron 103 pacientes, edad promedio en años (desviación estándar) 78 (10,4), 74,8% mujeres. La osteoporosis posmenopáusica (61,2%) y osteoporosis no especificada (20,4%), ambas con o sin fractura patológica, fueron los diagnósticos principales. En el 36,9%, la utilización de teriparatide y ácido zoledrónico fue acorde a las recomendaciones de las guías revisadas. La utilización de estos medicamentos en diagnósticos diferentes a osteoporosis posmenopáusica (43,7%) o como farmacoterapia inicial (36,9%) fueron las principales causas para ausencia de concordancia. Conclusiones: Sólo en el 36,9% de los casos revisados, la utilización de teriparatide o ácido zoledrónico se ajusta a las guías de organizaciones internacionales. La ausencia de concordancia se debe, especialmente a uso en diagnósticos diferentes a osteoporosis posmenopáusica y como farmacoterapia inicial.

ABSTRACT Introduction: Bisphosphonates are the first-line treatment of osteoporosis in which zoledronate is the most effective. Teriparatide (anabolic agent), due to high cost, should be restricted to the treatment of the most affected patients and after adequate treatment with bisphosphonates. Objective: To establish the percentage of patients with osteoporosis, in treatment with teriparatide or zoledronic acid in Colombia, that meet international organizations recommendations. Method: Retrospective drug utilization study, January 2012-December 2015, in patients with osteoporosis and treatment with teriparatide or zoledronic acid. The socio-demographic and clinical information and the degree of concordance of teriparatide or zoledronic acid use with recommendations from three international clinical guidelines were reviewed: National Osteoporosis Foundation, National Institute for Health and Clinical Excellence, and Scottish Intercollegiate Guidelines Network. Results: 103 patients were included, average age in years (standard deviation) 78 (10.4), 74.8% women. Postmenopausal osteoporosis (61.2%) and unspecified osteoporosis (20.4%), both with or without pathological fracture, were the main diagnoses. In 36.9%, the use of teriparatide and zoledronic acid was accord with the guidelines recommendations revised. The use of these drugs in diagnoses different to postmenopausal osteoporosis (43.7%) or initial pharmacotherapy (36.9%) were the main causes for concordance absence. Conclusions: Only 36.9% of the reviewed cases, the use of teriparatide or zoledronic acid was accord with international organizations guideliness. Concordance absence is due especially both to the use in diagnoses different to postmenopausal osteoporosis and initial pharmacotherapy.

New Antiresorptive Therapies for Postmenopausal Osteoporosis

Osteoporosis is a systemic skeletal disease whose risk increases with age and it is common among postmenopausal women. Currently, almost all pharmacological agents for osteoporosis target the bone resorption component of bone remodeling activity. Current antiresorptive agents are effective, but the effectiveness of some agents is limited by real or perceived intolerance, longterm adverse events (AEs), coexisting comorbidities, and inadequate long-term adherence. New antiresorptive therapies that may expand options for the prevention and treatment of osteoporosis include denosumab, combination of conjugated estrogen/bazedoxifene and cathepsin K inhibitors. However, the long-term efficacy and AEs of these antiresorptive therapies need to be confirmed in studies with a longer follow-up period.

Intravenous Zoledronate for a Patient with Paget's Disease

Paget's disease (PD) of bone is characterized by increase of bone resorption by atypical osteoclasts, followed by rapid new bone formation resulting in a disorganized mosaic bone. Although the pathophysiology is not fully understood, bisphosphonate, which is a potent anti-resorptive agent for treatment of osteoporosis, have been the most effective agents available for the treatment of PD. We report a case of PD of bone in a 49-year-old woman patient, who was treated with intravenous zoledronate.

Bone Biology and Anabolic Therapies for Bone: Current Status and Future Prospects

Bone is continuously remodelled at many sites asynchronously throughout the skeleton, with bone formation and resorption balanced at these sites to retain bone structure. Negative balance resulting in bone loss and osteoporosis, with consequent fractures, has mainly been prevented or treated by anti-resorptive drugs that inhibit osteoclast formation and/or activity, with new prospects now of anabolic treatments that restore bone that has been lost. The anabolic effectiveness of parathyroid hormone has been established, and an exciting new prospect is presented of neutralising antibody against the osteocyte protein, sclerostin. The cellular actions of these two anabolic treatments differ, and the mechanisms will need to be kept in mind in devising their best use. On present evidence it seems likely that treatment with either of these anabolic agents will need to be followed by anti-resorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for safe, effective anti-resorptive drugs.

Undertreatment of Osteoporosis Following Hip Fractures in Jeju Cohort Study

BACKGROUND: Osteoporosis treatment following hip fracture is well known to not enough. We previously performed intervention study for orthopaedic surgeon's education and reported twofold increase in osteoporosis detection and treatment rate observed between 2005 and 2007. This follow-up observational study was conducted to find out the rate in which a diagnostic workup and treatment for osteoporosis were done in patients with hip fracture. METHODS: Medical records and radiographs in patients who were older than 50 years and diagnosed as having femoral neck or intertrochanteric fractures at 8 hospitals in Jeju island, South Korea from 2008 to 2011 were reviewed. The numbers of patients who were studied with bone densitometry and who were treated for osteoporosis after the diagnosis of hip fracture were analyzed. RESULTS: Nine hundred forty five hip fractures (201 in 2008, 257 in 2009, 265 in 2010, and 304 in 2011) occurred in 191 men and 754 women during the study periods. The mean age of the patients was 79.7 years. The mean rate of osteoporosis detection using dual energy X-ray absorptiometry was 36.4% (344/945 hips) (ranged from 24.2% in 2009 to 40.5% in 2011). The mean initiation rate of osteoporosis treatment was 23.1% (218/945 hips) (ranged from 20% in 2009 to 29% in 2008). CONCLUSIONS: Detection and treatment rate of osteoporosis following hip fracture during follow-up periods was still not enough. Additional intervention studies are required to further improvement of osteoporosis treatment rates after hip fracture.

Moduladores seletivos do receptor estrogênico: novas moléculas e aplicações práticas / Selective estrogen receptor modulators: new molecules and practical uses

Os moduladores seletivos do receptor de estrogênio são moléculas que se ligam ao receptor estrogênico com ações agonistas e antagonistas, em tecidos específicos. Eles apresentam efeitos estrogênicos e antiestrogênicos em vários órgãos, o que lhes permite diferentes atuações clínicas específicas. As diferenças nas estruturas moleculares conferem propriedades diferentes de ligação ao receptor-alvo, resultando em diferenças nos efeitos terapêuticos e adversos. Desde a descoberta dos primeiros compostos, há 50 anos, vários outros têm sido estudados e são usados frequentemente por ginecologistas, oncologistas e mastologistas. O raloxifeno é aprovado para a prevenção e o tratamento de osteoporose na pós-menopausa e para o câncer de mama receptor de estrogênio positivo; o tamoxifeno, para prevenção e tratamento do câncer de mama receptor de estrogênio positivo na pós-menopausa; e o clomifeno, primeiro modulador seletivo com receptor de estrogênio a ser estudado e empregado clinicamente, para infertilidade. Outras moléculas como bazedoxifeno, lasofoxifeno e arzoxifeno vêm sendo estudadas e vêm se mostrando como alternativas eficazes, algumas com menos efeitos colaterais

Selective estrogen receptor modulators are molecules that bind to estrogen receptor with agonistic and antagonistic actions in specific tissues. They exert estrogenic and anti-estrogenic effects in several organs, allowing them to perform differently in specific clinical situations. The differences in molecular structures provide different binding properties to the target receptor, resulting in differences in therapeutic and adverse effects. Since the discovery of the first compounds 50 years ago, several others have been studied and are often used by gynecologists and oncologists, and mastologists. Raloxifene is approved for preventing and treating osteoporosis in postmenopausal women and for treating estrogen receptor-positive breast cancer; tamoxifen is used for preventing and treating estrogen receptor-positive postmenopausal breast cancer; and clomiphene, the first selective estrogen receptor modulator to be studied and clinically employed, is used for infertility treatment. Other molecules such as bazedoxifene, lasofoxifene and arzoxifene have been studied and shown to be effective alternatives, some with fewer side effects

Effects of D-003 (10 mg/day) on Bone Mineral Density of the Lumbar Spine and Femoral Neck in Postmenopausal Women: A Randomized, Double-Blinded Study

BACKGROUND/AIMS: Increased osteoclast activity is a pivotal finding in osteoporosis. This increase is mediated via the mevalonate-to-cholesterol pathway, which is involved in producing the intermediates required for osteoclast activity. D-003, a mixture of high molecular weight sugarcane wax acids, has been shown to inhibit cholesterol synthesis prior to mevalonate production, resulting in a reduction of bone loss and resorption in ovariectomized rats. Moreover, previous studies have demonstrated that short-term D-003 treatment reduces urinary excretion of deoxypyridinoline/creatinine in postmenopausal women. METHODS: We performed a double-blinded, placebo-controlled study to investigate the effects of D-003 (10 mg/day) treatment for 3 years on bone mineral density (BMD) in 83 postmenopausal women with low BMD. RESULTS: Over 3 years, D-003 treatment increased lumbar spine BMD (5.1%, p < 0.01) and improved osteoporosis-related quality of life scores as compared with placebo-treated controls. D-003 was also well tolerated; the frequency of adverse events in the bone, joints, or muscle with D-003 treatment (p < 0.05) was lower than in the placebo group. CONCLUSIONS: D-003 treatment (10 mg/day) for 3 years increased lumbar spine BMD and produced clinical improvements in postmenopausal women with low BMD. Further studies, however, will be required to confirm these results.