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A relevância e a abordagem consistente dos temas reunidos no Guia Prático em Osteometabolismo asseguraram a publicação dessa nova edição. Preparada pelos membros do Departamento de Metabolismo Ósseo e Mineral da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) e por seus colaboradores, oferece uma visão ainda mais detalhada sobre condições enfrentadas diariamente por clínicos e especialistas, como diabetes mellitus, osteoporose, hipertireoidismo e hipoparatireoidismo. Com isso, o guia mantém a sua condição como material de consulta e referência para profissionais da Endocrinologia e áreas relacionadas.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with a decline in quality of life and high morbidity and mortality. The presence of a VF is a significant risk factor for developing another fracture; however, most VFs are not clinically recognized and diagnosed. Vertebral fracture assessment by dual-energy X-ray absorptiometry is a low cost, low radiation, convenient, and reliable method to identify VFs. The finding of a previously unrecognized VF may change the assessment of fracture risk, diagnostic classification, and treatment strategies. Vertebral fracture assessment or radiographic lateral spine imaging should be repeated in patients with continued high risk for fracture (e.g., historical height loss >4 cm [>1.5 inches], self-reported but undocumented vertebral fracture, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent per day for greater than or equal to 3 months).

Latin America and the Caribbean region account for 8% of the world's total population. Experts from 18 countries were invited to contribute to this article to provide the best available data on the number, types, and quality of densitometry, DXA experts, the local/national incidence and prevalence of osteoporosis and fragility fractures, and other uses and information on the challenges and opportunities for quality densitometry with examples of local initiatives. Osteoporosis is the primary reason for densitometry in our region, which is not a priority for public health in most countries. Access and quality are major challenges, and there is a clear trend to concentrate on densitometry services in the largest cities. Urgent action is needed to face the rapidly increasing burden of osteoporosis in our region, including robust and up to date epidemiology, access to health professionals, and quality densitometry. Health professionals require better access to training, courses, and other activities at a more local or regional level.

INTRODUCTION/BACKGROUND: Hypophosphatasia is a rare inborn error of metabolism that presents with important foot and thigh pain due to stress fractures. The diagnose of the adult form is routinely neglected, even though it presents symptomatic and with persistent low serum alkaline phosphatase (ALP). CLINICAL CASE (DIAGNOSTIC EVALUATION, TRATMANET AND FUP): A 43-year-old amateur athlete woman presented with pain in the right femur without any local trauma. Physical examination evidenced prolonged right tight pain and no other findings. Bone mineral density evaluated by dual-energy x-ray absorptiometry was unremarkable. Biochemical investigations showed normal inorganic phosphate, calcium, zinc, and magnesium, but low ALP. The patient had six previous ALP measurements and all of them were below the lower limit of normality (46 a 116 U/L). These measurements were done in regular ob-gyn checkups with no further investigation or follow-up. In light of the hypophosphatasemia and pathologic fracture, the serum pyridoxal 5’-phosphate concentration was measured and found to be elevated 35,8 mcg/L (normal 5,0 a 30,0 mcg/L). CLINICAL LESSONS/CONCLUSION: Hypophosphatasia occurs due to a deactivating mutation (or mutations) of the gene encoding Tissue-Nonspecific Alkaline Phosphatase (TNSALP), leading to a global deficiency of TNSALP activity and inadequate skeletal mineralization and fractures. The adult form presents during middle age with stress fractures. The first complaints maybe foot pain, which is due to stress fractures of the metatarsals, and thigh pain, due to pseudo fractures of the femur. Our patient illustrates the importance of low serum ALP activity in the assessment of these patients. The correct diagnosis should help to avoid the use of traditional therapies for osteoporosis or osteomalacia, which would be ineffective or potentially harmful.

Aims We assessed the change from baseline in vitamin E, steroid hormones, adrenocorticotropic hormone (ACTH), and gonadotropins, overall and by lowest achieved low‐density lipoprotein‐cholesterol (LDL‐C) level, in patients with type 2 diabetes and dyslipidaemia after 12 weeks of treatment with evolocumab. Materials and Methods This was a prespecified analysis of vitamin E, cortisol, ACTH, gonadal hormones and gonadotropins in the 12‐week, placebo‐controlled BERSON trial of evolocumab in patients with type 2 diabetes and dyslipidaemia. In BERSON, 981 (451 in China) patients on daily atorvastatin 20 mg were randomized to placebo or one of two doses of evolocumab. We measured analyte levels at baseline and week 12 (vitamin E in all patients; steroid/gonadal hormones only in Chinese patients). Results In both the global and Chinese populations, absolute vitamin E levels decreased from baseline to week 12 by approximately 6 μmol/L (P, In this prespecified analysis of the BERSON study in Chinese and global patients with type 2 diabetes and dyslipidaemia, we assessed the change from baseline in vitamin E, steroid hormones, adrenocorticotropic hormone (ACTH), and gonadotropins, overall and by lowest achieved low‐density lipoprotein‐cholesterol (LDL‐C) level after 12 weeks of treatment with evolocumab. We found that evolocumab did not adversely affect vitamin E, steroid hormone or gonadotropin levels in the Chinese or global type 2 diabetic populations.

BACKGROUND: DXA is an accessible, non-invasive method, also used for body composition assessment, standing out for regional composition analysis. In clinical practice, the analysis of body composition is relevant by differentiating lean (fat-free) mass from fat mass. The higher the fat to lean mass ratio, the greater the obesity-related comorbidities. CLINICAL CASE: Case 1: A 22-year-old male, BMI 21kg/m2, with rheumatoid arthritis (RA) and on chronic glucocorticoid (GC) performed a DXA to evaluated body composition. The first analysis, during GC use, showed 26.1% fat (14.6kg) despite the low BMI. The patient, evolved stable from RA, and was able to stay out of GC for 2 years, with no other interventions. A new DXA showed a decrease in fat percentage to 12.6% (6.2kg), a reduction in total body weight (-7kg) and an increase in lean mass (+1.2kg). Within 16 months of GC reintroduction, the fat percentage increased up to 36.8% (23.8kg), the total weight increased by 15.6kg and the lean mass decreased by 2.1kg. Case 2: A 40-year-old male with hypogonadism showed 37% fat (33.8kg) on ​​first DXA evaluation. Testosterone replacement was started, and a new DXA was performed after 10 weeks, and although the total weight increased by 3.1kg, there was a decrease in fat mass to 33.5% (31.6kg) and an increase of 5.3kg in lean mass. After 3 years, there was a reduction to 27.1% of fat (24.5kg) and, after 4 years of therapy initiation, the percentage of fat was 26.9% (24.5kg). There was no change in diet or exercise. CONCLUSION: The exposed cases highlight the importance of body composition assessment in patients with conditions that interferes with energy metabolism. The patient on chronic GC use, after medication withdrawal, presented a significant decrease in fat mass, more pronounced in the android percentage. The reintroduction of the CG showed an increase in fat percentage, with android predominance. The patient with hypogonadism, in the second evaluation performed with only 10 weeks of treatment with testosterone, evolved with a reduction in fat mass associated with an increase in lean mass, besides a reduction in the android percentage. The reported cases illustrate everyday clinical situations in which disease vs. treatment significantly changes body composition. Assessment of body composition is essential in patients exposed to conditions that interfere with energy metabolism since obesity is associated with chronic comorbidities and cardiovascular outcomes.

Bisphosphonates (BPs) are the pioneer and gold standard drugs for osteoporosis treatment. The development of BPs started decades ago. There are four bisphosphonates in the osteoporosis market: alendronate, risedronate, ibandronate, and zolendronate. Pamidronate, an important BP, is used for the treatment of osteogenesis imperfecta ( ). shows the evolution of BPs discovery and approval for osteoporosis treatment. […] Osteoporosis treatment: the battle to be won

Background Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO’s clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg). Methods In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12—baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was Results HbA1c mean reductions were − 1.26% (90% CI − 1.7%, − 0.8%), − 1.12% (90% CI − 1.4%, − 0.8%), − 1.29% (90% CI − 1.6%, − 1.0%), and − 1.15% (90% CI − 1.5%, − 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of − 18.94 mg/dL, − 21.17 mg/dL, and − 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO’s “target” dose (5 mg) was confirmed. No safety concerns were identified. Conclusions These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg). Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).

Ethnicity is a known factor for DPP-4 inhibitors (DPP-4i)response in type 2 diabetes mellitus (T2DM). A bridging study was conducted to confirm the approved dosage of Evogliptin (EVO), in Korea (once daily 5mg) and the safety for the Brazilian population. In this randomized, double-blind, double-dummy, parallel trial, 146 T2DM patients (male: 50.7%; age: 51.5 ± 10.2 years; time from T2DM diagnosis: 1.7 ± 3.5 years; baseline HbA1c: 8.9 ± 0.9%) with inadequate glycemic control on diet and exercise were randomly assigned to a 12-week once daily treatment with EVO 2,5 mg, EVO 5 mg, EVO 10 mg or sitagliptin (SITA) 100 mg.T2DM patients aged 20 to 75 years, with 7.5% ≤ HbA1c ≤ 10.5% at screening, and who have not been on any hypoglycemic agent within 12 weeks prior to screening were eligible for the study. Subjects with fasting plasma glucose ≥ 300 mg/dL at screening in the presence of severe signs/symptoms of T2DM were excluded. Sample size was estimated to identify a clinically relevant HbA1c mean reduction ≥ 0,5% within each treatment group. Change from baseline to Week 12 (mean; 90% CI) in HbA1c (%) and, fasting plasma glucose levels (mg/dL) was calculated. Treatment effects on HbA1c and fasting glucose levels adjusted by baseline HbA1c, fasting plasma glucose and BMI were also estimated. The results confirmed the clinical benefit of a daily EVO 5,0 mg regimen in the Brazilian population. Disclosure A.C. Forti: None. J.S. Felício: None. L.A. Russo: None. J. Borges: None. A.R. Chacra: None. J.E. Salles: Board Member; Spouse/Partner; AstraZeneca, Merck & Co., Inc., Novo Nordisk A/S. Other Relationship; Spouse/Partner; Eurofarma Laboratórios S.A. C. Cercato: Board Member; Self; Novo Nordisk Inc. Research Support; Self; Eurofarma, Novo Nordisk Inc. Funding Eurofarma Laboratórios S.A.

RESUMOAs fraturas vertebrais são o tipo mais comum de fratura osteoporótica. As mulheres na pós-menopausa têm um risco aumentado de fraturas vertebrais osteoporóticas em comparação com as mulheres em idade fértil. As fraturas vertebrais estão associadas a um aumento na morbidade e mortalidade e à elevação do risco de fratura vertebral subsequente, independentemente da densidade mineral óssea. Apesar da ocorrência comum e das graves consequências das fraturas vertebrais, elas muitas vezes passam despercebidas ou são erroneamente diagnosticadas pelos radiologistas. Além disso, as fraturas vertebrais podem ser descritas com uma terminologia variável, que pode confundir em vez de esclarecer o médico solicitante. Foi feito um levantamento dos laudos das radiografias de coluna vertebral de um grupo de mulheres na pós-menopausa selecionadas para participar de um estudo de osteoporose no Centro de Pesquisa Clínica do Brasil. A análise descritiva avaliou a variabilidade dos laudos em sete pacientes. Quatro radiologistas gerais independentes emitiram laudos de avaliação das fraturas vertebrais por meio de uma análise cega. O objetivo deste estudo foi avaliar a consistência desses laudos. A análise descobriu uma acentuada variabilidade no diagnóstico das fraturas vertebrais e na terminologia usada para descrevê-las. Na prática clínica da comunidade, essa variabilidade poderia levar a diferenças no tratamento de pacientes com osteoporose, com o potencial de subtratamento ou tratamento exagerado, a depender das circunstâncias clínicas. Laudos precisos e inequívocos de fraturas vertebrais são susceptíveis de estar associados a melhores desfechos clínicos. ABSTRACTVertebral fractures are the single most common type of osteoporotic fracture. Postmenopausal women are at increased risk for osteoporotic vertebral fractures compared with women of childbearing age. Vertebral fractures are associated with an increase in morbidity, mortality, and high risk of a subsequent vertebral fracture, regardless of bone mineral density. Despite the common occurrence and serious consequences of vertebral fractures, they are often unrecognized or misdiagnosed by radiologists. Moreover, vertebral fractures may be described by variable terminology that can confuse rather than enlighten referring physicians. We conducted a survey of spine X-ray reports from a group of postmenopausal women screened for participation in a study of osteoporosis at Centro de Pesquisa Clínica do Brasil. A descriptive analysis evaluated the variability of reports in 7 patients. Four independent general radiologists issued reports assessing vertebral fractures through a blinded analysis. The objective of this study was to evaluate for consistency in these reports. The analysis found marked variability in the diagnosis of vertebral fractures and the terminology used to describe them. In community medical practices, such variability could lead to differences in the management of patients with osteoporosis, with the potential for undertreatment or overtreatment depending on clinical circumstances. Accurate and unambiguous reporting of vertebral fractures is likely to be associated with improved clinical outcomes.

Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with diminished quality of life and high morbidity and mortality. The presence of a VF, especially a recent one, is an important risk factor for developing another fracture. However, most VFs are not clinically recognized. VF assessment by dual-energy X-ray absorptiometry is a convenient, low-cost, low-radiation, reliable method to identify VFs during bone mineral density measurement. The finding of a previously unrecognized VF may change the diagnostic classification, assessment of fracture risk, and treatment strategies. This paper focuses on the utility of VF assessment in clinical practice.

Objetivo Apresentar uma atualização sobre o diagnóstico e tratamento da hipovitaminose D baseada nas mais recentes evidências científicas. Materiais e métodos O Departamento de Metabolismo Ósseo e Mineral da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) foi convidado a conceber um documento seguindo as normas do Programa Diretrizes da Associação Médica Brasileira (AMB). A busca dos dados foi realizada por meio do PubMed, Lilacs e SciELO e foi feita uma classificação das evidências em níveis de recomendação, de acordo com a força científica por tipo de estudo. Conclusão Foi apresentada uma atualização científica a respeito da hipovitaminose D que servirá de base para o diagnóstico e tratamento dessa condição no Brasil.

The technique of body composition by dual-energy X-ray absorptiometry (DXA) has been used for several years in the research environment. Its ability to accurately and precisely measure lean, fat, and mineral composition in various body compartments has been well validated. Furthermore, the technique is widely available to clinical patients on existing DXA instruments throughout the world through the use of specific software packages and scanning algorithms. There have been few clear statements regarding the clinical indications for body composition measurement in patients outside the research setting. This is in part because of the lack of specific documented interventions that would be affected by body composition test results, beyond usual clinical advice. We have examined a few of the most common, specific scenarios (HIV therapy, sarcopenia, bariatric surgery, obesity) and proposed indications for body composition assessment. We have also discussed contraindications to body composition testing.

Satisfactory healing of the osteoporotic fracture is critically important to functional recovery, morbidity, and quality of life. Some therapies for osteoporosis may affect the processes associated with bone repair. For example, bisphosphonates in experimental models are associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. For the osteoanabolic agent teriparatide, case reports and a randomized trial have produced mixed results, but they are consistent with a positive impact of teriparatide on fracture healing. Some of the agents currently being developed for osteoporosis, notably sclerostin and DKK1 antibodies have shown a beneficial effect on fracture healing. At this point, therefore, there is no evidence that osteoporosis therapies are detrimental to fracture healing with some promising experimental evidence for positive effects on healing, notably for those agents whose actions are primarily anabolic. A consolidação adequada da fratura osteoporótica é essencial para recuperação funcional, morbidade e qualidade de vida. Alguns tratamentos para osteoporose podem afetar os processos associados ao reparo ósseo. Por exemplo, os bisfosfonatos, em modelos experimentais, estão associados com aumento do tamanho do calo e a mineralização, reduzindo o remodelamento do calo e melhorando a força mecânica. Tratamento com bisfosfonato, local ou sistêmico, pode melhorar a fixação de implantes. Não foi observado impacto negativo na consolidação da fratura, mesmo após uma cirurgia maior ou quando administrado imediatamente após a fratura. Relatos e um estudo randomizado com o osteoanabólico teriparatida produziram resultados mistos, mas que são consistentes com o impacto positivo da teriparatida na consolidação da fratura. Algumas das drogas que estão sendo desenvolvidas no momento para osteoporose, como anticorpos para esclerotina e DKK1, têm mostrado efeito benéfico na consolidação da fratura. No estágio atual, portanto, não há evidência de que terapias para osteoporose impeçam a consolidação da fratura, mas existem algumas evidências experimentais promissoras de efeito positivo na consolidação, especialmente daqueles agentes cuja ação é primariamente anabólica.

INTRODUÇÃO: Há um grande número de estudos mostrando que o treinamento de força tem um efeito positivo sobre a densidade mineral óssea (DMO). Porém, existem poucos estudos comparando a DMO entre praticantes de hidroginástica e treinamento de força. OBJETIVO: Comparar, em uma análise transversal, a DMO de mulheres praticantes de treinamento de força com mulheres praticantes de hidroginástica, na pós-menopausa. MÉTODOS: A amostra foi composta de 63 mulheres, divididas em três grupos: treinamento de força (FORÇA: n = 15; 51,4 ± 2,7 anos), hidroginástica (HIDRO: n = 22; 54,5 ± 3,3 anos) e controles não treinadas (CONTROLE: n = 26; 52,0 ± 3,3 anos). Todas as voluntárias estavam em terapia de reposição hormonal há no mínimo um ano. Os grupos FORÇA e HIDRO treinavam há pelo menos um ano antes do início do estudo (média de anos de treinamento - FORÇA: 4,5 ± 2,0; HIDRO: 4,2 ± 2,2). RESULTADOS: O grupo FORÇA apresentou maior DMO de corpo total, colo femoral e coluna lombar L2-L4 quando comparado ao grupo-controle (todos P < 0,05). O grupo HIDRO apresentou maior DMO no corpo total, quadril total e coluna lombar L2-L4 quando comparado ao grupo-controle (todos P < 0,05). Entretanto, não foram observadas diferenças entre os grupos FORÇA e HIDRO em nenhum dos sítios avaliados. CONCLUSÕES: Estes achados sugerem que não apenas o treinamento de força, mas também a hidroginástica podem ser estratégias não farmacológicas para prevenção da perda de DMO em mulheres na pós-menopausa. INTRODUCTION: Many studies have shown that resistance training has a positive effect on bone mineral density (BMD). However, few studies have compared the BMD of individuals undergoing resistance training and those training aquatic weight-bearing exercises. OBJECTIVE: To compare, in a cross-sectional study, the BMD of postmenopausal women undergoing resistance training and postmenopausal women training aquatic weight-bearing exercises. METHODS: The sample comprised 63 women divided into the following three groups: resistance training (STRENGTH: n = 15; 51.4 ± 2.7 years); aquatic weight-bearing exercises (WA-TER: n = 22; 54.5 ± 3.3 years); and non-trained controls (CONTROL: n = 26; 52.0 ± 3.3 years). All volunteers were on hormone replacement therapy for at least one year. The STRENGTH and WATER groups were training for at least one year prior to study beginning (mean years of training - STRENGTH: 4.5 ± 2.0; WATER: 4.2 ± 2.2). RESULTS: The STRENGTH group had higher BMD of total body, femoral neck, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). The WATER group had higher BMD of total body, total hip, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). However, no difference was observed between the STRENGTH and WATER groups regarding the sites assessed. CONCLUSIONS: Those findings suggest that not only the resistance training, but also aquatic weight-bearing exercises might be a non-pharmacological strategy to prevent BMD loss in postmenopausal women.

The high prevalence of obesity is a worldwide problem associated with multiple comorbidities, including cardiovascular diseases. Vitamin D deficiency with secondary hyperparathyroidism is common in obese individuals and can be aggravated after bariatric surgery. Moreover, there is no consensus on the optimal supplementation dose of vitamin D in postbariatric surgical patients. We present new data on the variability of 25(OH)D response to supplementation in postmenopausal obese women. It is important to recognize and treat vitamin D deficiency before bariatric surgery to avoid postoperative complications, such as metabolic bone disease with associated high fracture risk. The objective of this article is to discuss the bone metabolism consequences of vitamin D deficiency after bariatric surgery.

Background: Daily nitrogen-containing bisphosphonates have shown antifracture efficacy in many studies of postmenopausal osteoporosis. However, current dosing schedules are often inconvenient or impractical for patients. Efforts to reduce dosing frequency to improve adherence (ie, compliance and persistence), and therefore treatment outcomes, are ongoing. Although a number of trial designs can be used to consider the efficacy of therapy, comparing the efficacy of different regimens should only be undertaken in purposefully designed head-to-head studies. Objective: This article summarizes the design and conduct of clinical studies that have investigated alternative bisphosphonate regimens and those that have directly compared different approved bisphosphonates. It also explores the implications for future studies of postmenopausal osteoporosis treatment. Methods: Using the terms bisphosphonate, daily, weekly , and monthly , a search (completed in 2006) of the PubMed database was conducted to identify primary English-language publications of pertinent studies comparing either novel with established regimens of the same bisphosphonates or different established bisphosphonates. Results: The first option is the equivalence or noninferiority bridging study for comparison of new treatment regimens versus the established regimen of the same bisphosphonate, known as the active comparator. Four such studies have led to the registration of novel bisphosphonate dosing regimens designed to provide easier dosing alternatives for patients. The second option is the active comparator study, which compares one bisphosphonate with the most prescribed weekly bisphosphonate. Weekly dosed oral alendronate has previously been shown to be superior (for bone mineral density gains) to daily and weekly dosed oral risedronate. An ongoing noninferiority study, Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention, is comparing weekly alendronate with ibandronate, a monthly oral bisphosphonate. Conclusions: The exploration of new dosing schedules and formulations aims to identify the optimal bisphosphonate regimen for postmenopausal osteoporosis. To achieve this, careful consideration must be given to the choice of a scientifically valid study design that effectively, and ethically, meets the study objectives. Given the concerns regarding placebo-controlled antifracture studies, 2 alternative study designs should be considered, both using validated surrogate end points (bone mineral density and biochemical markers of bone turnover) as the principal mode of assessment.

The diagnosis of osteoporosis and monitoring of treatment is a challenge for physicians due to the large number of available tests and complexities of interpretation. Bone mineral density (BMD) testing is a non-invasive measurement to assess skeletal health. The "gold-standard" technology for diagnosis and monitoring is dual-energy X-ray absorptiometry (DXA) of the spine, hip, or forearm. Fracture risk can be predicted using DXA and other technologies at many skeletal sites. Despite guidelines for selecting patients for BMD testing and identifying those most likely to benefit from treatment, many patients are not being tested or receiving therapy. Even patients with very high risk of fracture, such as those on long-term glucocorticoid therapy or with prevalent fragility fractures, are often not managed appropriately. The optimal testing strategy varies according to local availability and affordability of BMD testing. The role of BMD testing to monitor therapy is still being defined, and interpretation of serial studies requires special attention to instrument calibration, acquisition technique, analysis, and precision assessment. BMD is usually reported as a T-score, the standard deviation variance of the patient's BMD compared to a normal young-adult reference population. BMD in postmenopausal women is classified as normal, osteopenia, or osteoporosis according to criteria established by the World Health Organization. Standardized methodologies are being developed to establish cost-effective intervention thresholds for pharmacological therapy based on T-score combined with clinical risk factors for fracture.

Osteoporose é uma doença caracterizada pela baixa massa óssea e alterações de micro arquitetura do tecido ósseo, levando ao aumento da fragilidade óssea e aumento do risco de fratura. Apesar da pesquisa em osteoporose ter focalizado principalmente no papel da perda óssea na população idosa, está começando a ficar claro que a quantidade de osso que é ganho durante o crescimento é também um determinante importante de resistência futura para fraturas. Portanto, interesse considerável está sendo colocado na definição de estratégias preventivas que otimizam o ganho de massa óssea durante a infância e adolescência. O conhecimento dos determinantes responsáveis pelas variações fisiológicas e genéticas, na acumulação óssea nas crianças, irá levar aos melhores meios para o diagnóstico precoce e tratamento da osteoporose. Este artigo revê as técnicas disponíveis para a medida da massa óssea em crianças e os maiores determinantes e doenças que influenciam a aquisição óssea durante a infância e adolescência. Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence. Universidade Catolica de Brasilia Federal University of São Paulo EPM Division of Endocrinology Fleury - Diagnostic Medicine UNIFESP, EPM, Division of Endocrinology SciELO

Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes a person to increased fracture risk. Fractures are often associated with increased morbidity, higher mortality, loss of function and even psychological consequences. Pharmacotherapeutic interventions (e.g., bisphosphonates, selective estrogen receptor modulators, calcitonin, and teriparatide) in women with postmenopausal osteoporosis provide substantial reduction in fracture risk over and above risk reduction with calcium and vitamin D supplementation alone. The importance of nutritional support along with an appropriate exercise regimen, avoiding smoking and excessive alcohol use is to be emphasized along with the pharmacologic approach to osteoporosis. Despite the effectiveness of therapy with pharmacologic agents, most patients who start therapy do not remain on treatment for more than 1 year.

O objetivo deste estudo foi comparar a densidade mineral ossea (DMO) em mulheres praticantes de hidroginastica e mulheres sedentarias. Fizeram parte da amostra 48 mulheres, sendo 22 praticantes de hidroginastica (54,5 ± 3,3 anos), e 26 sedentarias (52,0 ± 3,3). Todas as participantes do estudo estavam na pos-menopausa e fazendo terapia de reposicao hormonal ha, no minimo, um ano. A densitometria ossea foi feita por um aparelho da marca lunar, modelo DPX-IQ. Foi obtida a DMO da coluna lombar (L2-L4), do femur (colo do femur e quadril total) e antebraco. Para a analise dos dados utilizou-se, como tratamento estatistico, a analise de variância (one-way ANOVA) para amostras independentes. Nas praticantes de hidroginastica comparadas com as sedentarias, a DMO foi mais elevada (p

25 Sergio was known to everyone as Sergio. He did not need a last name because his first name was always enough. Sergio was a beacon for excellence, dedication, accomplishment, friendship, humor, and all else that truly counts in life. It is with those thoughts that we pay tribute to Sergio who passed away too early, at the age of 49 yr, but who left us with remembrances that will last our lifetimes and beyond. Sergio received his medical degree from the Fundac~ao T ecnico Educacional Souza Marques in Rio de Janeiro and trained in orthopedics. Soon thereafter, he dedicated his career to further the development of bone densitometry in Brazil and throughout the world. In 1990, Sergio founded and directed the Osteoporosis Diagnosis and Research Center of Esp irito Santo (CEDOES). As a founding member of the Brazilian Society for Clinical Densitometry, he was elected President in 1995 and again in 2007. As a founding member of the Latin American Society for Clinical Densitometry, SOLAD, he served as President from 2001 to 2003. With an iron will but a gentle hand, an indomitable spirit, a twinkle of the eye, and a good jokedin any languagedSergio brought together several disparate elements of the Brazilian bone community. He masterfully conceived a single entity that would officially bring them all together. Initially, it was BRADOO, a national meeting of the Sociedade Brasileira de Densitometria Clinica (SBDens), Sociedade Brasiliera de Osteoporose (SOBRAO), and Sociedade Brasileira para o Estudo do Metabolismo Osseo e Mineral (SOBEMOM). But, a single consolidated meeting was not enough for Sergio. By sheer will that overcame any and all objections, Sergio forged the 3 societies (SBDens, SOBRAO, and SOBEMOM) into a single organization, Associac~ao Brasileira de Avaliac~ao Ossea e Osteometabolismo (ABRASSO), which now features 1500 members. It is one of his crowning achievements. The first meeting of ABRASSO in Belo Horizonte, November, 2011, was the last meeting that Sergio organized. It was a spectacular success. At the most recent meeting of the International Society for Clinical Densitometry (ISCD) in Los Angeles, March, 2012, we honored Sergio by wearing ABRASSO caps.

Objective: To conduct a literature review on the diagnosis and management of Paget’s disease of bone. Materials and methods: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including “D”, are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. Conclusion: We present a scientific statement on Paget’s disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment. Arq Bras Endocrinol Metab. 2014;58(6):587-99 Objetivo: Conduzir uma atualização das últimas evidências científicas a respeito da apresentação, diagnóstico e manejo clínico da doença de Paget óssea. Materiais e métodos: Este documento foi concebido pelo Departamento de Metabolismo Ósseo da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) a partir daquele oriundo do Programa de Diretrizes da Associação Médica Brasileira (AMB). Realizamos uma revisão dos artigos mais relevantes obtidos nos bancos de dados PubMed e Cochrane, além de abstracts apresentados nos encontros anuais da Endocrine Society, Sociedade Brasileira de Endocrinologia e da American Society for Bone and Mineral Research dos últimos cinco anos e classificamos as evidências em níveis de recomendações de acordo com a força científica por tipo de estudo, adaptando o primeiro relato do “Oxford Centre for Evidence-based Medicine”. Todos os graus de recomendação, incluindo-se o “D”, foram baseados em evidência científica, sendo as diferenças entre o A, B, C e D devidas exclusivamente ao desenho empregado na geração da evidência. Conclusão: Apresentamos uma atualização científica a respeito da doença de Paget óssea, classificando e graduando em níveis de recomendações as principais evidências científicas sobre as suas causas, as variadas formas de apresentação, seu diagnóstico e tratamento.

OBJETIVO: Conduzir uma atualização das últimas evidências científicas a respeito da apresentação, do diagnóstico e do manejo clínico e cirúrgico do hiperparatireoidismo primário clássico e normocalcêmico. MATERIAIS E MÉTODOS: Este documento foi concebido pelo Departamento de Metabolismo Ósseo da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) a partir daquele oriundo do Programa de Diretrizes da Associação Médica Brasileira (AMB) da SBEM. Realizamos uma revisão dos artigos mais relevantes obtidos nos bancos de dados PubMed e Cochrane, além de abstracts apresentados nos encontros anuais da Endocrine Society, da Sociedade Brasileira de Endocrinologia e da American Society for Bone and Mineral Research dos últimos cinco anos, e classificamos as evidências em níveis de recomendações de acordo com a força científica por tipo de estudo, adaptando o primeiro relato do Oxford Centre for Evidence-based Medicine. Todos os graus de recomendação, incluindo-se o D, foram basea-dos em evidência científica, sendo as diferenças entre o A, B, C e D devidas exclusivamente ao desenho empregado na geração da evidência. CONCLUSÃO: Apresentamos uma atualização científica a respeito do hiperparatireoidismo primário, classificando e graduando em níveis de recomendações as principais evidências científicas sobre as suas causas, as variadas formas de apresentação, seu diagnóstico e tratamento. OBJECTIVE: To conduct a literature review on the diagnosis and management of primary hyperparathyroidism including the classical hipercalcemic form as well as the normocalcemic variant. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society for Endocrinology as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including D, are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on primary hyperparathyroidism providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment. University of Pernambuco Medical School Ministry of Health Federal University of São Paulo Medical School Federal University of Parana Medical School University of Brasilia Medical School Catholic University of Brasilia Columbia University College of Physicians & Surgeons UNIFESP, Medical School SciELO

Osteoporosis is a common skeletal disease that increases the risk of fracture, with serious clinical and economic consequences. It can be diagnosed by dual-energy X-ray absorptiometry (DXA), even before a fracture has occurred, using the World Health Organization (WHO) criteria according to the patient's T-score. The WHO has also developed a fracture risk assessment tool (FRAX) to estimate the 10-year probability of major osteoporotic fracture (clinical spine, hip, proximal humerus, and distal forearm) and hip fracture, using clinical risk factors for fracture and femoral neck bone mineral density (BMD), if available. Cost-effective pharmacological agents that have been proven to reduce fracture risk in patients at high risk for fracture are now widely available. However, despite great progress in the management of osteoporosis, it remains a disease that is underrecognized and undertreated; if treatment is started, persistence is often poor, with only about 50% of patients who are prescribed medication for osteoporosis still taking it 1 year later. Even when treatment is taken correctly and for a sufficient length of time for the patient to benefit from reduction in fracture risk, there may nevertheless be limitations in effectiveness (note the lack of evidence for reduction in the risk of hip fractures or other nonvertebral fractures with some agents), limitations in the duration of therapy (e.g., no more than 24 months of lifetime teriparatide in the US), and concerns regarding long-term safety, such as atypical femur fractures and osteonecrosis of the jaw with bisphosphonates. For all of these reasons, the goal of reducing the global burden of osteoporotic fractures is not being fully achieved. This special issue of the Journal of Osteoporosis describes new and emerging approaches to treatment that offer the potential to reduce the risk of fractures or manage their consequences better than what is currently observed in clinical practice. In recent years, our understanding of the pathophysiology of osteoporosis and the regulation of bone remodeling at the molecular level have undergone tremendous advances, leading to the investigation of drugs that target specific molecules in order to modulate the bone remodeling process. For example, the discovery that receptor activator of nuclear factor kappa B ligand (RANKL) is the principal regulator of osteoclastic bone resorption led to the development of denosumab, a fully human monoclonal antibody to RANKL. This potent antiresorptive agent, administered as a 60 mg subcutaneous injection every 6 months, recently received regulatory approval for the treatment of women with postmenopausal osteoporosis (PMO) at high risk for fracture. It has been shown to increase BMD, reduce bone turnover marker levels, and reduce the risk of vertebral fractures, hip fractures, and nonvertebral fractures in women with PMO. Wnt signaling initiated by the binding of Wnt proteins to the low density lipoprotein-related protein (LRP5/6)-frizzled receptor complex has recently been recognized as an important upregulator of osteoblastic bone formation; sclerostin and Dickkopf-1 (DKK-1) are natural inhibitors of Wnt signaling. In this issue, J. J. Mason and B. O. Williams describe a rare genetic disorder, sclerosteosis, resulting from a mutation of the SOST gene that encodes for sclerostin, and van Buchem disease, a related disorder caused by a mutation closely linked to SOST on chromosome 17q11.2. Patients with sclerosteosis and van Buchem disease have high bone mass due to downregulation of sclerostin, suggesting that a therapeutic agent that downregulates sclerostin in a controllable fashion might be a potent osteoanabolic treatment for patients with osteoporosis. Mason and Williams review many of the studies that have enhanced our understanding of the regulators of Wnt signaling and lead to the investigation of compounds with potential therapeutic applications through their effects on sclerostin or DKK1. A fascinating new finding, yet to be fully elucidated, is that serotonin produced by enterochromaffin cells in the duodenum also downregulates Wnt signaling, raising the possibility that modulation of serotonin production or activity might also be an effective treatment for patients with osteoporosis. In a related paper by S. Silverman in this issue, the preclinical and clinical studies of sclerostin inhibition are presented. The drugs used to treat osteoporosis are generally considered to be in 1 of 2 categories—antiresorptive (e.g, bisphosphonates) or osteoanabolic (e.g., teriparatide). Interestingly, some drugs may “uncouple,” at least in part, the closely related processes of bone resorption and formation. Strontium ranelate may be such a drug. Another, perhaps, is odanacatib, an investigational agent that inhibits cathepsin K, a protease produced by osteoclasts that is largely responsible for the degradation of the bone collagen matrix. J. L. Perez-Castrillon et al. review what is now known about the role of cathepsin K in health and disease, followed by data from phase 1 and phase 2 clinical trials with odanacatib. This drug is currently under investigation in a large phase 3 clinical trial to evaluate antifracture efficacy in women with PMO. Other papers in this issue cover new developments concerning skeletal heath in areas as diverse as bisphosphonate nanoparticles, melatonin, and thalassemia. The papers in the issue were selected from many excellent submissions. We give our thanks to all authors of these submissions and to the numerous reviewers who kindly donated their time and expertise in helping select and revise those published here. E. Michael Lewiecki Manuel Diaz Curiel Joao Lindolfo Borges Annie Kung Maria Luisa Brandi Hans Peter Dimai

The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported.This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events.MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, noninferiority study in postmenopausal women aged 55 to85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed.A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were -75.5% with monthly ibandronate and -81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported inor=30% of patients per group during this 1-year study.The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.

Descrevemos as posições oficiais da Sociedade Brasileira de Densitometria Clínica (SBDens) para a realização e o relato do exame de densitometria óssea. Essas posições foram obtidas por consenso em encontro realizado em São Paulo no ano de 2006. A SBDens contou com o apoio de várias sociedades científicas descritas no texto. We describe the official positions of the Brazilian Society for Clinical Densitometry (SBDens) for the performance and report of the bone mineral density testing. These positions were obtained by consensus in a meeting at São Paulo in 2006. SBDens positions were supported by other scientific societies described in the text.

The use of placebo control groups (e.g., subjects using calcium and vitamin D) in osteoporosis trials with subjects at high risk for fracture has been systematically questioned by institutional review boards (IRBs). Regulatory agencies, on the other hand, continue to not only recommend but also require that placebo-controlled trials be presented for the registration of new drugs for osteoporosis treatment. The Declaration of Helsinki and its updates have upheld the principle that protection of research subjects' rights is of primary concern. Nevertheless, even the Declaration keeps clearly opening the possibility of using placebo-control designs if it is justified for "compelling and scientifically sound methodological reasons." The use of intermediary endpoints or surrogates to establish the efficacy or safety of new medications in the management of osteoporosis is currently considered scientifically insufficient. This concept has led regulatory agencies, such as the Food and Drug Administration in the United States and the European Medicines Agency in the European Union, to require "fragility fracture reduction" as the primary endpoint in clinical trials for the registration of new drugs. Superiority or noninferiority trials are alternatives to placebo-controlled designs. However, factors such as sample size, cost, and statistical limitations render these models impractical for the registration of new medications for osteoporosis. We recommend collaboration among regulatory agencies, IRBs, scientists, and ethicists on the design of clinical trials for the registration of new medications for reduction of fracture risk. Delay in developing mutually acceptable models may impair scientific development in the field and possibly deprive patients of potentially beneficial treatments.

On December 2, 2013, it was called our attention that the case report () contained few paragraphs that bear a likeness to a further review (). This occurred inadvertently when we entrusted the literature and a draft of this review () to others co-authors. Although we were not aware of theses similarities between the case report and this review. We nevertheless take full responsibility for this error. The primary objective of our case report () is to describe a accelerated [...]