Long-term consequences of osteoporosis therapy with bisphosphonates

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO)

ABSTRACT Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.

Use of aromatase inhibitors in patients with breast cancer is associated with deterioration of bone microarchitecture and density

ABSTRACT Objective: To evaluate changes in bone density and architecture in postmenopausal women with breast cancer (BC) and use of aromatase inhibitor (AI). Subjects and methods: Thirty-four postmenopausal women with BC, without bone metastasis, renal function impairment and who were not receiving bone-active drugs were selected from a population of 523 outpatients treated for BC. According to the presence of hormonal receptors, HER2 and Ki67, seventeen had positive hormonal receptors and received anastrozole (AI group), and seventeen were triple-negative receptors (non-AI group), previously treated with chemotherapy. Areal bone mineral density (aBMD) and vertebral fracture assessment (VFA) analyses were performed by DXA; vBMD and bone microarchitecture were evaluated by HR-pQCT. Fracture risk was estimated using the FRAX tool. Results: No patient referred previous low-impact fracture, and VFA detected one moderate vertebral fracture in a non-AI patient. AI patients showed lower aBMD and BMD T-scores at the hip and 33% radius and a higher proportion of osteoporosis diagnosis on DXA (47%) vs non-AI (17.6%). AI group had significantly lower values for vBMD at the entire, cortical and trabecular bone compartments, cortical and trabecular thickness and BV/TV. They also had a higher risk for major fractures and for hip fractures estimated by FRAX. Several HR-pQCT parameters evaluated at distal radius and distal tibia were significantly associated with fracture risk. Conclusion: AI is associated with alterations in bone density and microarchitecture of both the cortical and trabecular compartments. These findings explain the overall increase in fracture risk in this specific population.

Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC)

ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL

Consensus - reference ranges of vitamin D [25(OH)D] from the Brazilian medical societies. Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC/ML) and Brazilian Society of Endocrinology and Metabolism (SBEM) / Posicionamento oficial da Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML) e da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) sobre intervalos de referência da vitamina D [25(OH)D]

ABSTRACT Introduction: Vitamin D is considered a pre-hormone and plays a crucial role in calcium homeostasis and, consequently, in bone health. The best source of vitamin D is the skin in response to sunlight. Only small amounts of this vitamin are found in some foods (especially fatty fish), which makes availability of vitamin D in the diet limited. Brazilian population studies show that the prevalence of hypovitaminosis D in our country is high. Objective: To define the reference intervals for vitamin D [25(OH)D]. Discussion: Consensus of specialists - literature review. Conclusion: The standardization of reference intervals is fundamental for the correct diagnosis and treatment of hypovitaminosis D.

RESUMO Introdução: A vitamina D é considerada um pré-hormônio e apresenta papel crucial na homeostase do cálcio e, consequentemente, na saúde óssea. A maior fonte de vitamina D é a pele, em resposta à luz solar. Apenas pequenas quantidades dessa vitamina são encontradas em alguns alimentos (especialmente peixes gordurosos), o que faz com que a disponibilidade da vitamina D na dieta seja limitada. Estudos populacionais brasileiros demonstram que a prevalência da hipovitaminose D no nosso país é elevada. Objetivo: Definição dos intervalos de referência para vitamina D [25(OH)D]. Discussão: Consenso de especialistas - revisão da literatura. Conclusão: A padronização dos intervalos de referência é fundamental para o correto diagnóstico e tratamento da hipovitaminose D.

Calcium intake: good for the bones but bad for the heart? An analysis of clinical studies

ABSTRACT The proper dietary calcium intake and calcium supplementation, when indicated, are important factors in the acquisition of peak bone mass during youth and in the prevention of fractures in old age. In addition to its deposition in bone, calcium confers an increase in its resistance and exhibits important activities in different enzymatic pathways in the body (e.g., neural, hormonal, muscle-related and blood clotting pathways). Thus, calcium supplementation can directly or indirectly affect important functions in the body, such as the control of blood pressure, plasma glucose, body weight, lipid profile and endothelial function. Since one publication reported increased cardiovascular risk due to calcium supplementation, many researchers have studied whether this risk actually exists; the results are conflicting, and the involved mechanisms are uncertain. However, studies that have evaluated the influence of the consumption of foods rich in calcium have reported no increase in the cardiovascular risk, which suggests that nutritional intake should be prioritized as a method for supplementation and that the use of calcium supplements should be reserved for patients who truly need supplementation and are unable to achieve the recommended daily nutritional intake of calcium.

Importance of bone assessment and prevention of osteoporotic fracture in patients with prostate cancer in the gonadotropic hormone analogues use / Importância da avaliação óssea e da prevenção da fratura osteoporótica em pacientes com câncer de proìstata em uso de anaìlogos do hormônio gonadotrófico

The antiandrogenic therapy (ADT) for prostate cancer represents an additional risk factor for the development of osteoporosis and fragility fractures. Still, bone health of patients on ADT is often not evaluated. After literature research we found that simple preventive measures can prevent bone loss in these patients, resulting in more cost-effective solutions to the public health system and family when compared to the treatment of fractures.

A terapia antiandrogênica (TAD) para câncer de próstata representa um fator de risco adicional para o desenvolvimento de osteoporose e fraturas de fragilidade. Mesmo assim, a saúde óssea dos pacientes sob TAD frequentemente não é avaliada. Após pesquisa na literatura, observamos que medidas preventivas simples podem prevenir a perda de massa óssea nestes pacientes, resultando em soluções mais custo-efetivas para o Sistema Público de Saúde e familiares quando comparadas ao tratamento das fraturas.

Análise de idosos ambulatoriais quanto ao estado nutricional, sarcopenia, função renal e densidade óssea / Analysis of elderly outpatients in relation to nutritional status, sarcopenia, renal function, and bone density

Objetivo : Avaliar relações entre estado nutricional, sarcopenia e osteoporose em idosas.Sujeitos e métodos : Estudamos 44 mulheres, 67-94 anos, mediante miniavaliação nutricional (MAN), filtração glomerular (FG) corr. 1,73 m2, índice de massa corporal (IMC), circunferência da panturrilha e braquial (CP e CB), densidade mineral óssea e composição corporal, DXA (massa gorda – MG; massa magra – MM). Aferimos sarcopenia: IMM = MM MSS + MIS/altura2. Utilizamos o coeficiente de correlação de Pearson, e p < 0,05 como significativo.Resultados : MNA e IMM se correlacionaram positivamente com IMC, CP, CB e MG. A idade influenciou negativamente FG corr., IMC, MG, IMM e CP. Quatorze tinham história de fraturas osteoporóticas. O mais baixo T-score foi diretamente relacionado a MAN e MG.Conclusões : O envelhecimento acarretou o declínio da FG, MG e massa muscular; a circunferência da panturrilha e braquial refletiu estado nutricional e composição corporal; e as grandes influências na DMO foram estado nutricional e MG. Arq Bras Endocrinol Metab. 2014;58(3):226-31.

Objectives : To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women.Subjects and methods : We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m2, body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height2. We used the Pearson correlation coefficient, p < 0.05 as significant.Results : MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG.Conclusions The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.Arq Bras Endocrinol Metab. 2014;58(3):226-31.

Localizaçäo dos aferentes primários que inervam a articulaçäo temporomandibular do macaco Cebus Apella / Localization of primary afferent neurons that innervate the temporomandibular joint in Cebus monkey

A origem da inervaçäo sensitiva da articulaçäo temporomandibular (ATM) é motivo de controvérsia. Livros clássicos de anatomia indicam que os corpos neuronais responsáveis por essa inervaçäo estariam localizados no núcleo mesencefálico do nervo trigêmeo. Entretanto, estudos realizados em mamíferos inferiores indicam que esses neurônios estariam localizados no gânglio trigeminal. Neste trabalho, empregando a técnica de traçado de vias nervosas mediante a utilizaçäo de peroxidase do rábano silvestre (HRP), estudou-se a inervaçäo da ATM do primata Cebus apella. Os resultados mostram que os corpos neuronais responsáveis pela inervaçäo sensitiva da ATM nesses animais se localizam apenas no gânglio trigeminal

Estudo radiográfico da incidência de bifurcaçöes do canal radicular de incisivos inferiores / Radiographic study of the incidence of bifurcations in the root canal of mandibular incisors

Uma das principais razöes do insucesso da terapia endodôntica dos incisivos inferiores é a falta de conhecimento da anatomia da cavidade pulpar. A morfologia dos canais radiculares dos incisivos inferiores tem sido estudada por muitos autores. Há uma divergência de resultados que varia entre 53 por cento de canais duplos encontrados por Fischer e 11 por cento encontrados por Madeira & Hetem. A origem dessas discrepâncias está relacionada com os diferentes métodos utilizados. No presente trabalho foram usados 1081 incisivos centrais e 1034 incisivos laterais. Os dentes foram dispostos lado a lado sobre filmes para radiografias panorâmicas e radiografados no sentido vestíbulo-lingual e mésio-distal. As radiografias foram analisadas sobre um negatoscópio onde encontramos 11,3 por cento de canais duplos nos incisivos centrais e 9,3 por cento nos incisivos laterais inferiores. Concluímos que 10,3 por cento dos incisivos inferiores apresentaram duplicaçäo de seu canal radicular. O clínico deve realizar sempre um exame radiográfico em várias angulaçöes para detectar a duplicaçäo do canal dos incisivos inferiores, antes de iniciar a terapia endodôntica

Ruídos articulares e o tratamento das desordens temporomandibulares / Joint sounds and the treatment of temporomandibular disorders

O ruído articular é um dos sinais da DTM que indica alteraçäo na ATM e permite estabelecer o diagnóstico clínico da patologia articular. A avaliaçäo de 34 pacientes indicou que 70,58 por cento apresentavam algum tipo de ruído, sendo o estalido o mais comum (54,16 por cento). A persistência dos ruídos articulares é o principal fator relacionado ao insucesso do tratamento da DTM

Organizaçäo morfológica e morfométrica do núcleo motor do nervo trigêmeo do macaco Cebus / Morphological and morphometric organization of the trigeminal motor nucleus in the Cebus monkey

As características morfológicas e morfométricas dos neurônios do núcleo motor do nervo trigêmeo foram estudadas em cinco macacos Cebus apella. Os motoneurônios trigeminais foram identificados pela injeçäo de horseradish peroxidase (HRP) nos músculos masséter, temporal, pterigoideo medial e ventre anterior do músculo digástrico. Do ponto de vista citoarquitetônico, o núcleo motor do nervo trigêmeo foi subdividido numa porçäo lateral e outra, menor, ventromedial. O diâmetro dos motoneurônios, corados pela técnica de Nissl, variou entre 16,15 e 52,73 µm, sendo a média de 32,89 µm. A distribuiçäo de parâmetros como área, diâmetro mínimo e diâmetro médio foi unimodal, o que impossibilitou uma diferenciaçäo morfométrica entre motoneurônios alfa e gama

Avaliaçäo clínica e radiográfica da articulaçäo temporomandibular em indivíduos com perda de dentes posteriores e interferências oclusais, antes e após o tratamento oclusal / Clinical and radiographic evaluation of changes in the temporomandibular joint following loss of posterior teeth and occlusal interference

A sintomatologia, o tipo mais eficiente de tratamento, e a posiçäo final do côndilo após o tratamento oclusal foram verificados em um grupo de 67 pacientes, por meio de questionário e exames clínico e radiográfico. A posiçäo condilar obtida pelas radiografias foi avaliada pelas medidas realizadas com um analisador de imagem computadorizado (Minimop). Os resultados permitiram concluir que: 1) a dor na cabeça foi a queixa principal dos pacientes com disfunçäo temporomandibular; 2) a placa de mordida e ajuste oclusal säo as modalidades mais eficientes de tratamento; 3) a posiçäo final do côndilo na fossa mandibular é ligeiramente à frente do centro da fossa mandibular para a maioria das articulaçöes examinadas

Anatomia da face: bases anátomo-funcionais para a prática odontológica / Anatomy of the face: functional anatomical bases for the dental practice

Este livro é dirigido principalmente aos estudantes de Odontologia e também de grande valor aos profissionais da área. Seu conteúdo volta-se näo apenas para princípios anatômicos, mas também para alguns aspectos de aplicaçäo clínica. Juntos, eles compöem indispensável base científica para a prática odontológica. Os capítulos säo escritos na sequência: a cabeça, os músculos faciais, TMJ, boca, vasos sanguíneos e nervos da face. As 138 ilustraçöes säo fotografias e desenhos feito diretamente dos modelos