Osteoporosis is a very common disease, and data on its epidemiology is important for health care strategy implementation. Brazil is a developing country; its population is aging, leading to an expected increase in hip fractures and their undesirable consequences. Assess the incidence of osteoporotic hip fractures and subsequent mortality in Southern Brazil as part of a large epidemiological study aiming to reinforce the data for FRAX Brazil. This study evaluated all admissions for fragility hip fractures between April 1, 2010, and March 31, 2012, in the city of Joinville, including both genders of patients 50 years old or older, which corresponded to 19.2% of the local population. Joinville was chosen because it is the third largest city in the south of Brazil, with a representative population predominantly composed of descendants of European immigrants. There were 213 cases of hip fractures, predominantly in Caucasians (n = 204, 96.7%) whose mean age was 77.7, ± 10.5, of which 143 (67.1%) were women (79.5 ± 9.6 years) and 70 (32.9%) were men (74 ± 11.3 years). The annual incidence of hip fractures was 268.8 for women and 153.0 for men/100,000 inhabitants. In the 60 to 64-year group, the overall incidence was 92.1/100,000, with an age-related increase of 1410.1/100,000 in the 80 to 84-year group. The mortality rate during hospitalization was 7.5%, and 25% died during the 12 months following their fractures. The incidence of hip fractures among the oldest in this predominantly Caucasian population living in Southern Brazil was similar to that of European populations from the northern hemisphere. The annual incidence of fragility hip fractures among people in their 80s was 59 times higher than that among people in their 50s. The mortality rate was 4.3 times higher in the first year after hip fracture than in the age-related local population.

Hip fracture incidence rates in three representative geographic areas in Brazil over a period of 2 years (2010–2012) were assessed for the first time. Estimated incidence rates varied regionally, and markedly differed from those previously reported. Thus, national guidelines as well as FRAX Brazil should be revised in light of this new data. To determine the annual incidence of hip fractures in individuals aged 50 years and over, living in 3 cities located in different regions of the country. To investigate the age, gender, and regional differences in fracture rates. Based on the obtained data, to estimate the national incidence of hip fractures resulting from osteoporosis, in order to improve prevention strategies. Retrospective, observational study including all patients aged ≥ 50 years admitted in hospitals because of a hip fracture in three cities (Belem, Joinville, and Vitoria) from representative geographic areas in Brazil from 2010 to 2012. Data were obtained from medical records in those cities. We analyzed incidence rates (crude and age- and gender-standardized rates) for hip fractures. There were 1025 (310 in men and 715 in women) hip fractures in the over 50-year-old merged population from the three cities. The crude incidence rate for hip fracture was 103.3/100,000 (95% confidence interval [CI = 97.0; 109.7), in men 77.4/100,000 (95% CI = 68.8; 86.0), and in women 125.2/100,000 (95% CI = 116.0; 134.4). Incidence standardized for age and gender was 105.9 cases per 100,000 persons per year (95% CI = 99.4; 112.4); 78.5 cases per 100,000 (95% CI = 69.8; 87.3) in men and 130.6 cases 100,000 in women (95% CI = 121.0, 140.2) per year. Belem, located in the equatorial region (latitude 1° 27′ S), had significantly lower crude and age-adjusted incidence than Joinville (latitude 26° 18′ S) and Vitoria (latitude 20° 19′ S), which were no different from each other. The incidence of fractures increased exponentially with age, and women had about twice the risk of fractures than men. Hip fracture mainly affects elderly women and presents great variability in incidence between the different regions in Brazil. The incidence of hip fractures in Brazil differed markedly from that reported previously, so that national guidelines and the FRAX model for Brazil should be revised.

Background/Aims: Osteoporosis is a bone metabolic disease that affects mostly post-menopausal women. There has been shown that vitamin K (VK) supplementation during menopause may decrease bone loss as well as risk of bone breaking. Aiming to clarify the beneficial role of VK in bone metabolism during menopause, we investigated mineral metabolism and bone ultrastructure of ovariectomized (OVX) mice. Methods: To determine the effects chronic use of VK in bone structure and mineral metabolism in OVX mice, we used several methods, such as DXA, µCTScan, and SEM as well as biomolecular techniques, such as ELISA and qRT-PCR. In addition, complete analysis of serum hormonal and other molecules associated to bone and lipid metabolism were evaluated overview the effects of VK in menopause murine model. Results: VK treatment significantly affects Pi metabolism independently of OVX, changing Pi plasma, urinary output, balance, and Pi bone mass. Interestingly, VK also increased VLDL in mice independently of castration. In addition, VK increased compact bone mass in OVX mice when we evaluated it by DXA, histomorphometry, µCTScanning. VK increased bone formation markers, osteocalcin, HYP- osteocalcin, and AP whereas it decreased bone resorption markers, such as urinary DPD/creatinine ratio and plasmatic TRAP. Surprisingly, SEM images revealed that VK treatment led to amelioration of microfractures observed in OVX untreated controls. In addition, SHAM operated VK treated mice exhibited higher number of migrating osteoblasts and in situ secretion of AP. OVX led to decreased to in situ secretion of AP that was restored by VK treatment. Moreover, VK treatment increased mRNA expression of bone Calbindin 28KDa independently of OVX. Conclusion: VK treatment in OVX mice exhibited beneficial effects on bone ultrastructure, mostly by altering osteoblastic function and secretion of organic bone matrix. Therefore, VK could be useful to treat osteopenic/osteoporotic patients.

Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010–2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations associated to SNP XbaI c454-351A>G on ESR1 gene is enhanced in both obese (higher BMI) and elder women. Taken together, these results suggested that XbaI c454-351A>G SNP is associated to changes in lipid profile, particularly in serum TG and TL, in this cohort of post-menopausal woman. Also, this paper shows another link between obesity and BC corroborating the current thesis that both diseases are interlinked.

OBJECTIVE:This open, randomized and blinded parallel-group multicenter study evaluated the efficacy of Actonel(®) (35 mg) plus calcium/vitamin D versus calcium/vitamin D alone for preserving bone mineral density (BMD) in postmenopausal women with Colles fractures.METHODS:Patients with a Colles fracture for seven days were randomized to receive either Actonel(®) (35 mg) once a week plus calcium/vitamin D (ACD group) or calcium/vitamin D alone (CD group). The patients were evaluated after 90 and 180 days of treatment.RESULTS:59 ACD patients and 56 CD patients completed all the evaluations. At the end of the study, the BMD of the radius at the fracture location showed a negative change in the CD group (32.8%). The loss of BMD in the ACD group (20.8%) was slightly less than that in the CD group. There was a difference in the proportions of patients with BMD losses at the end of the study period in the two treatment groups, in favor of the ACD group, although this was not statistically significant. There was no significant difference in radiological identification of callus formation between the treatment groups. In the majority of the patients, the callus could be radiologically identified after 90 days.CONCLUSION:Postmenopausal women with Colles fractures who received risedronate sodium plus calcium/vitamin D did not show any significant difference in BMD loss in forearm fractures, in comparison with those who received calcium/vitamin D alone. Risedronate presented a tendency toward a protective effect regarding BMD loss due to immobilization. The time taken for fracture consolidation to be achieved was unaffected.

Este estudo multicêntrico, randomizado, aberto, grupo paralelo avaliou a eficácia de Actonel® 35 mg mais cálcio/vitamina D versus cálcio/vitamina D isoladamente na preservação da densidade mineral óssea (DMO) em mulheres pós‐menopausadas com fratura de Colles. Pacientes com fratura de Colles em sete dias foram aleatoriamente designadas para receber Actonel® 35 mg semanalmente mais cálcio/vitamina D (Grupo AO [GAO]) ou cálcio/vitamina D (grupo O [GO]) isoladamente. As pacientes foram avaliadas após 90 e 180 dias de tratamento. Completaram as avaliações 59 pacientes no GAO e 56 no OG. No fim do estudo, a DMO do rádio no local da fratura mostrou variação negativa no GO (32,8%) que foi discretamente menor no GAO (20,8%), assim como uma perda menor na DMO no GAO comparado com o OG. Houve diferença na proporção de paciente com perda da DMO no fim do estudo nos dois grupos de tratamento em favor do GAO, apesar de não estatisticamente significante. Não houve diferença significativa na identificação radiológica da formação do calo entre os grupos de tratamento. Na maioria das pacientes a identificação radiológica do calo ocorreu depois de 90 dias. Mulheres pós‐menopausadas com fratura de Colles que receberam risedronato sódico, além do cálcio/vitamina D, comparado com cálcio/vitamina D não mostraram diferença significativa na perda da DMO na fratura do antebraço, com tendência de efeito protetor do risedronato na perda da DMO devido à imobilização. O tempo até a consolidação da fratura não foi afetado. This open, randomized and blinded parallel‐group multicenter study evaluated the efficacy of Actonel® (35 mg) plus calcium/vitamin D versus calcium/vitamin D alone for preserving bone mineral density (BMD) in postmenopausal women with Colles fractures. Patients with a Colles fracture for seven days were randomized to receive either Actonel® (35 mg) once a week plus calcium/vitamin D (ACD group) or calcium/vitamin D alone (CD group). The patients were evaluated after 90 and 180 days of treatment. Completed all the evaluations 59 ACD patients and 56 CD patients. At the end of the study, the BMD of the radius at the fracture location showed a negative change in the CD group (32.8%). The loss of BMD in the ACD group (20.8%) was slightly less than in the CD group. There was a difference in the proportions of patients with BMD losses at the end of the study period in the two treatment groups, in favor of the ACD group, although this was not statistically significant. There was no significant difference in radiological identification of callus formation between the treatment groups. In the majority of the patients, the callus could be radiologically identified after 90 days. Postmenopausal women with Colles fractures who received risedronate sodium plus calcium/vitamin D did not show any significant difference in BMD loss in forearm fractures, in comparison with those who received calcium/vitamin D alone. Risedronate presented a tendency towards a protective effect regarding BMD loss due to immobilization. The time taken for fracture consolidation to be achieved was unaffected.

Baixa massa óssea medida pelo exame de densitometria óssea (T-score) é um dado objetivo importante para o diagnóstico de osteoporose em pacientes que não tiveram fratura. Baixa densidade mineral óssea (DMO) é, isoladamente, o melhor preditor do risco de fratura. Uma metanálise de 19 estudos com mais de 50 mil indivíduos mostrou que o risco de fratura aumenta de 1,5 a 3 vezes para cada diminuição do desvio padrão (DP) do T-score na DMO(1). Os valores obtidos na DMO para o T-score estimam fratura da mesma forma que a medida da pressão arterial estima o acidente vascular cerebral e com maior sensibilidade que a dosagem do colesterol sérico prediz infarto do miocárdio (1). Embora a determinação da DMO em um local do esqueleto possa também estimar fraturas em outros locais, a sensibilidade da DMO como estimador do risco de fratura em um determinado local (por exemplo, quadril, coluna, rádio distal) melhora se sua medição for feita no próprio local. O maior coeficiente de risco é demonstrado no quadril onde uma diminuição de 1 DP no T-score aumenta o risco de fratura em 2,6 vezes(1). Assim, um indivíduo com T-score de -2 no quadril terá um risco estimado de fratura no quadril de 2,6², ou seja, mais que seis vezes o risco em relação a um indivíduo com T-score de 0 DP. Para a coluna, este coeficiente de estimativa é menor (1,6) e se um indivíduo apresentar, por exemplo, um T-score de -3 na DMO de L1-L4, seu risco calculado para fraturas de quadril será de 1,6³ em relação a um indivíduo com T‑score de 0 DP no mesmo local. Os riscos avaliados nestas duas comparações são denominados riscos relativos (RR) sitioespecíficos, pois a comparação é feita entre a diferença nos riscos dos T-scores de dois pacientes (um relativo ao outro). Mesmo levando em conta que o T-score seja de grande auxílio na tomada da decisão clínica, seu papel como elemento para estimativas do risco de fraturas depende fortemente de como seus valores são interpretados. Embora a definição operacional densitométrica adotada pela Organização Mundial de Saúde (OMS) para o diagnóstico da osteoporose seja uma DMO menor que 2,5 desvios-padrão abaixo do pico estimado de massa óssea (T-score ≤ -2,5), a maioria das fraturas (número absoluto) ocorre em mulheres com T-score maior que – 2,5 (2). O T-score obtido na densitometria óssea pode ter também diferentes interpretações quando utilizado para avaliar o risco de fratura em pacientes com idades diversas. O valor do T-score obtido em uma mulher com 50 anos de idade tem implicações diferentes na avaliação do risco de fratura quando comparado ao mesmo valor em uma mulher de 80 anos. Para um mesmo valor de DMO, uma idade mais avançada torna-se um melhor preditor do risco de fratura. As razões pelas quais a idade aumenta o risco para fraturas ainda não estão bem definidas, porém, fatores contribuintes incluem uma maior probabilidade de quedas e alterações na qualidade óssea (por exemplo, maturação do colágeno, perda da organização da microarquitetura óssea). Uma fratura prévia por fragilidade também é um fator de risco independente da DMO para novas fraturas (3). Estudos populacionais e avaliações dos braços “placebo” dos ensaios clínicos farmacológicos demonstraram que uma fratura de quadril prévia dobra o risco de nova fratura de quadril e uma fratura vertebral prévia aumenta de 4 a 19 vezes o risco de nova fratura vertebral.

O emprego clínico da densitometria óssea confunde-se com o desenvolvimento dos conhecimentos científicos no campo da osteoporose. Até meados dos anos 1980, a osteoporose figurava unicamente entre as manifestações humanas vinculadas a uma longa existência. Já no início dos anos 1990, impulsionada pela possibilidade de estratificar indivíduos de acordo com o gradiente de risco para fraturas, a ciência lançou-se numa cruzada na busca de intervenções farmacológicas capazes de impedir as perdas de massa óssea características do processo de envelhecimento humano e, um pouco mais tarde, também para estimular a atividade osteogênica. Vias de regulação do balanço ósseo foram (e vêm sendo) identificadas e novos recursos terapêuticos e diagnósticos foram desenvolvidos, alavancados pela densitometria óssea. A definição operacional da osteoporose, ainda hoje utilizada em todo o mundo como variável insubstituível na prática médica, foi proposta em 1994 pela Organização Mundial da Saúde (OMS) (1). O critério da OMS baseia‑se em achados de densidade mineral óssea (DMO) por absorciometria de dupla emissão de raios X (DXA), limitados à coluna lombar, colo femoral, fêmur total ou rádio distal (33%). A Tabela 1 resume os critérios de estratificação propostos pela OMS. Desde então, várias são as iniciativas para padronizar o uso clínico, interpretação e prática da densitometria. No Brasil, a Sociedade Brasileira de Densitometria Clínica (SBDens), em estreita vinculação científica com a International Society for Clinical Densitometry (ISCD), vem, desde 1993, conduzindo programas de qualificação e certificação profissionais amplamente reconhecidos pela comunidade científica.

The Designed for intravenous (IV) Ibandronate reNal safety Evaluation (DIVINE) study was a 1-year prospective, randomized, open label, multi-center study that evaluated the renal safety of quarterly (every 3 months) ibandronate IV injection given over 15-30s compared with infusion given over 15 min, and weekly oral alendronate, in women with postmenopausal osteoporosis (PMO) at increased risk for renal disease. Both injection and infusion of IV ibandronate showed comparable safety to alendronate, with only small changes in serum creatinine (sCr) for each treatment group, and AEs were generally comparable between groups. All three treatments had similar effects on renal function, measured by change in baseline of the glomerular filtration rate; the ibandronate IV injection group was noninferior to the ibandronate IV infusion and weekly oral alendronate groups at 9 months, with similar results at 1 year. The results of this study demonstrate the profile of IV ibandronate, which allows it to be dosed as an IV injection in the primary care setting without the need for an infusion, even in patients with pre-existing hypertension or diabetes mellitus.

Low bone mineral density (BMD) has been described in human immunodeficiency virus (HIV)-infected patients, but data on associated factors are still unclear, and to our knowledge, no reports are available in Brazil. Our goal was to evaluate BMD in HIV patients attending an outpatient clinic in Vitoria, Brazil. A sectional study was performed in 300 HIV-infected patients to measure BMD by dual-energy X-ray absorptiometry (DXA). Age, gender, anthropometric parameters, nadir and current CD4 cell count, HIV viral load, smoking habit, and current antiretroviral therapy (ART) associations were investigated by multivariable analysis. Based on World Health Organization T-score ranges, low BMD (T-score <-1.0 standard deviation [SD] in postmenopausal women and men aged 50 and older or Z-score <- 2.0 SD in premenopausal women and men below the age of 50) was detected in 54.7% (95% confidence interval: 49.1-60.3%) of the 300 enrolled patients. The observed median age was 46 yr (interquartile range: 39-52), 58% were male, 88.5% were on ART, and 21.4% smoked. The following factors were identified, by multiple logistic modeling, as being independently associated with low BMD: (1) male gender (4.6 [1.28-16.39]), (2) body mass index lower than 25 kg/m(2) (2.9 [1.31-6.49]), (3) menopause (13.4 [2.53-71.12]), and (4) HIV-1 undetectable viral load (7.9 [1.96-32.25]). Conversely, zidovudine (0.2 [0.04-0.85]) and nevirapine (0.1 [0.02-0.38]) use were inversely associated with low BMD. Low BMD was frequently found in our cohort of about 300 Brazilian HIV-infected subjects. This study supports the need for periodic DXA testing in HIV outpatient clinics.

In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain.

Bone disorders have been described in patients chronically infected with human immunodeficiency virus (HIV). A case of spontaneous supracondylar femoral fracture that occurred in a 58-year-old monk during meditation is reported. His AIDS disease was controlled with combination antiretroviral therapy. Vitamin D and calcium had been added 3yr before since osteoporosis was detected by dual-energy X-ray absorptiometry (DXA). At the time of the fracture, the patient was on treatment with 35mg every week of sodium risedronate, 1000mg of calcium, and 400IU of Vitamin D every day. Clinical use of DXA for HIV patients should be considered as a routine measure to help reducing risk for fractures.

The epidemiology of osteoporotic fractures varies widely among countries and is primarily related to differences in the population and utilization of public healthcare services. Since 1994, over 200 studies about osteoporosis and fractures have been conducted in Brazil, among which 60 have described the current epidemiological status. This work is a compilation of studies published in scientific journals (PubMed, MedLine, Lilacs, SciELO Database) with the respective highlights. Overall, these studies show moderate incidence of hip fracture in subjects over 50 years old. However, the prevalence of all types of bone fragility fracture is higher, ranging from 11% to 23.8%. In addition, there is a high incidence of recurrent falls, which are the main extra-skeletal factor associated with these fractures. According to the national studies, 12 months after femoral fractures, the mortality rate ranged between 21.5% and 30%, and there was also a high rate of physical impairment, deterioration of the quality of life and excessive burden to the healthcare system. Considering its high prevalence and associated mortality and physical impairment, osteoporosis and its main consequence, bone fragility fractures, must be considered a major public health problem in our country.

Background: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terns 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 a) weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previ ously reported.Objective: 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 with-drawal and gastrointestinal (GI) adverse events.Methods: 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 to <85 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 month, 6 months + 7 days, and 12 months, serum concentrations of makes of bone resorption (C-telopeptide of the a chain of type I collagen [sCTX]) and bone formation (Serum N-terminal propeptides of type I 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.Results: 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 in <= 30% of patients per group during this 1-year-study.Conclusion: The data front these postmenopausal women with osteoporosis suggest that once-monthly 1.50-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. (Clin Tber. 2009;31:751-761) (C) 2009 Excerpta Medica Inc.

With the evolution of bone densitometry, differences in technologies, acquisition techniques, reference databases, reporting methods, diagnostic criteria and terminology have developed and the International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences, the latest in 2007. The Brazilian Society for Clinical Densitometry (SBDens), with support from many Brazilian societies interested in bone health, gathered numerous specialists to discuss the ISCD proposals and to evaluate the validity of the extension of those norms to Brazilian population. The SBDens reunion of consensus made a very useful document to help the understanding and interpretation of bone densitometry and other methods of bone assessment.

Peripheral assessment of bone density using photon absorptiometry techniques has been available for over 40 yr. The initial use of radio-isotopes as the photon source has been replaced by the use of X-ray technology. A wide variety of models of single- or dual-energy X-ray measurement tools have been made available for purchase, although not all are still commercially available. The Official Positions of the International Society for Clinical Densitometry (ISCD) have been developed following a systematic review of the literature by an ISCD task force and a subsequent Position Development Conference. These cover the technological diversity among peripheral dual-energy X-ray absorptiometry (pDXA) devices; define whether pDXA can be used for fracture risk assessment and/or to diagnose osteoporosis; examine whether pDXA can be used to initiate treatment and/or monitor treatment; provide recommendations for pDXA reporting; and review quality assurance and quality control necessary for effective use of pDXA.