Farnesyl Diphosphate Synthase Gene Associated with Loss of Bone Mass Density and Alendronate Treatment Failure in Patients with Primary Osteoporosis.

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; p = 0.026) and TH (CC = -2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.

The Relationship between Bone Mineral Densitometry and Visceral Adiposity Index in Postmenopausal Women / A relação entre a densitometria mineral óssea e o índice de adiposidade visceral em mulheres na pós-menopausa

Abstract Objective It was aimed to compare visceral adiposity index (VAI) levels in patients with normal bone mineral density (BMD), osteopenia, and osteoporosis. Methods One hundred twenty postmenopausal women (40 with normal BMD, 40 with osteopenia, and 40 with osteoporosis) between the ages of 50 to 70 years were included in the study. For females, the VAI was calculated using the formula (waist circumference [WC]/[36.58 + (1.89 x body mass index (BMI))]) x (1.52/High-density lipoprotein [HDL]-cholesterol [mmol/L]) x (triglyceride [TG]/0.81 [mmol/L]). Results The time of menopause from the beginning was similar in all groups. Waist circumference was found to be higher in those with normal BMD than in the osteopenic and osteoporotic groups (p = 0.018 and p < 0.001, respectively), and it was also higher in the osteopenic group than in the osteoporotic group (p = 0.003). Height and body weight, BMI, blood pressure, insulin, glucose, HDL-cholesterol, and homeostasis model assessment-insulin resistance (HOMA-IR) levels were similar in all groups. Triglyceride levels were found to be higher in the normal BMD group, compared with the osteoporotic group (p = 0.005). The level of VAI was detected as higher in those with normal BMD, compared with the women with osteoporosis (p = 0.002). Additionally, the correlation analysis showed a positive correlation between dual-energy X-ray absorptiometry (DXA) spine T-scores, WC, VAI, and a negative correlation between DXA spine T-scores and age. Conclusion In our study, we found higher VAI levels in those with normal BMD, compared with women with osteoporosis. We consider that further studies with a larger sample size will be beneficial in elucidating the entity.

Resumo Objetivo O objetivo foi comparar os níveis de índice de adiposidade visceral (IVA) em pacientes com densidade mineral óssea (DMO) normal osteopenia e osteoporose. Métodos Cento e vinte mulheres na pós-menopausa (40 com DMO normal 40 com osteopenia e 40 com osteoporose) com idades entre 50 e 70 anos foram incluídas no estudo. Para o sexo feminino o VAI foi calculado pela fórmula (circunferência da cintura [CC]/[36 58 + (1 89 x índice de massa corporal (IMC))]) x (1 52/lipoproteína de alta densidade [HDL]-colesterol [mmol/L]) x (triglicerídeo [TG]/0 81 [mmol/L]). Resultados O tempo de menopausa desde o início foi semelhante em todos os grupos. A circunferência da cintura foi maior naqueles com DMO normal do que nos grupos osteopênicos e osteoporóticos (p = 0 018 e p < 0 001 respectivamente) e também foi maior no grupo osteopênico do que no grupo osteoporótico (p = 0 003) . Altura e peso corporal IMC pressão arterial insulina glicose HDL-colesterol e os níveis de avaliação do modelo de homeostase-resistência à insulina (HOMA-IR) foram semelhantes em todos os grupos. Os níveis de triglicerídeos foram maiores no grupo DMO normal em comparação com o grupo osteoporótico (p = 0 005). O nível de VAI foi detectado como maior naquelas com DMO normal em comparação com as mulheres com osteoporose (p = 0 002). Além disso a análise de correlação mostrou uma correlação positiva entre a absorciometria de raios-X de dupla energia (DXA) nas pontuações T da coluna CC VAI e uma correlação negativa entre as pontuações T da coluna DXA e a idade. Conclusão Em nosso estudo encontramos níveis mais elevados de VAI naquelas com DMO normal em comparação com mulheres com osteoporose. Consideramos que novos estudos com maior tamanho amostral serão benéficos na elucidação da entidade.

Anogenital index and bone mineral density associations after natural and surgical menopause: a preliminary study

SUMMARY OBJECTIVE: The aim of this study was to evaluate postmenopausal women to determine whether an anogenital index (AGI) is associated with bone mineral density (BMD) based on the hypothesis that the effects of menopause are similar for both. METHODS: A total of 338 generally healthy postmenopausal women who were referred for a routine annual check and 140 women who met the inclusion criteria were enrolled in the study. Based on the menopausal status, the women were classified into natural menopause and surgical menopause. AGI was calculated by dividing anogenital distance by body mass index. The BMD of the femoral neck, body of the femur, and lumbar spine (L1 and L2) was measured using dual-energy x-ray absorptiometry. RESULTS: There was a statistically significant and same-directional correlation between age and AGI for all cases (r=0.234 and p=0.005). The AGI level decreased as the parity increased (r=-0.582 and p<0.001). The AGI level decreased significantly as the menopause duration was prolonged (r=0.288 and p<0.001). While there was no statistically significant correlation between L2-L4 BMD and AGI (p=0.128), as the femur and femoral neck BMD levels increased, the AGI level increased statistically significantly (r=0.330 and p<0.001, r=0.292 and p<0.001). CONCLUSION: The AGI levels in healthy postmenopausal women give preliminary information about their BMD status. A decrease in AGI levels may predict lower BMD in postmenopausal women. Further larger and well-controlled studies may be required to determine the relationship between AGI and BMD in the future.

Clinical impact of misinterpretation of dual-energy X-ray absorptiometry during the evaluation of osteoporotic patients.

Osteoporosis is a highly prevalent systemic skeletal disorder leading to decreased bone strength and increased susceptibility to fragility fracture. The global burden of osteoporosis negatively impacts health systems around the world, and the estimation of millions of individuals at high risk for fracture in 2010 will double by the year 2040. There are many techniques to evaluate bone mineral density, but the preferred method in clinical practice is dual-energy X-ray absorptiometry (DXA). This method, despite offering multiple advantages, can lead us to a wrong diagnosis if we do not take into account certain clinical and technical considerations. The objective of this review is to analyze the different aspects that we must consider when, as clinicians, we have to evaluate a densitometric report. These aspects are presented as technical factors influencing DXA results and patients' conditions limiting DXA interpretation.

Mandibular cortical index in the screening of postmenopausal at low mineral density risk: a systematic review.

OBJECTIVES: This systematic literature review addressed the use of mandibular cortical index (MCI), assessed by panoramic radiography, for the identification of postmenopausal women at risk of osteoporosis. METHODS: Databases were searched for original research studies published from September 2010 to September 2020 using the following keywords: "postmenopausal osteoporosis" and synonyms combined with "panoramic radiography" and synonyms. Only English language manuscripts and studies pertaining to the MCI were selected. RESULTS: A total of 24 studies were included. The publications were highly heterogeneous in terms of the subject of interest, i.e. the MCI, with some studies comparing the usefulness of the MCI using panoramic radiography and using cone beam computed tomography, and others comparing different radiomorphometric indexes developed for panoramic radiography. CONCLUSIONS: Based on the literature included in this systematic review, we conclude that the MCI is useful as an auxiliary tool for identifying postmenopausal females at risk of low bone mineral density (BMD), as it correlates with skeletal BMD measured by dual X-ray absorptiometry. Nevertheless, other radiomorphometric indexes obtained from panoramic radiographs, such as panoramic mandibular index, mental index, and mandibular cortical width, are also valuable as auxiliary tools in the identification of postmenopausal females at risk, as they also correlate with BMD. Thus, it is not possible to affirm which index is the most reliable for the identification of postmenopausal females considering the literature screened. PROSPERO registration systematic review CRD42020208152.

Association between bile acid metabolism and bone mineral density in postmenopausal women

OBJECTIVES: Previous studies have not shown any correlation between bile acid metabolism and bone mineral density (BMD) in women with postmenopausal osteoporosis. Thus, the current study evaluated the association between bile acid levels as well as BMD and bone turnover marker levels in this group of women. METHODS: This single-center cross-sectional study included 150 postmenopausal Chinese women. According to BMD, the participants were divided into three groups: osteoporosis group, osteopenia group, and healthy control group. Serum bile acid, fibroblast growth factor 19 (FGF19), and bone turnover biomarker levels were assessed. Moreover, the concentrations of parathyroid hormone, 25-hydroxy vitamin D [25(OH)D], procollagen type I N-peptide (P1NP), and beta-CrossLaps of type I collagen containing cross-linked C-terminal telopeptide (β-CTX) were evaluated. The BMD of the lumbar spine and proximal femur were examined via dual-energy X-ray absorptiometry. RESULTS: The serum total bile acid levels in the osteoporosis and osteopenia groups (5.28±1.56 and 5.31±1.56 umol/L, respectively) were significantly lower than that in the healthy control group (6.33±2.04 umol/L; p=0.002 and 0.018, respectively). Serum bile acid level was positively associated with the BMD of the lumbar spine, femoral neck, and total hip. However, it negatively correlated with β-CTX concentration. Moreover, no correlation was observed between bile acid and P1NP levels, and the levels of the other biomarkers that were measured did not differ between the groups. CONCLUSION: Serum bile acid was positively correlated with BMD and negatively correlated with bone turnover biomarkers reflecting bone absorption in postmenopausal women. Thus, bile acid may play an important role in bone metabolism.

Comparative efficacy of bone anabolic therapies in women with postmenopausal osteoporosis: A systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis. METHODS: Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome. RESULTS: Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments. CONCLUSIONS: Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.

The 17ß-oestradiol treatment minimizes the adverse effects of protein restriction on bone parameters in ovariectomized Wistar rats: Relevance to osteoporosis and the menopause.

OBJECTIVES: Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17ß-oestradiol. METHODS: Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17ß-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy. RESULTS: The results showed that protein restriction negatively affected body chemical composition and bone metabolism by the sex hormone deficiency condition in the OVX group. The association between undernutrition and hormone deficiency led to bone and muscle mass loss and increased the fragility of the bone (as well as decreasing relative femoral weight, bone mineral density, femoral elasticity, peak stress, and stress at offset yield). Although protein restriction induced more severe adverse effects compared with the controls, the combination with HRT showed an improvement in minimizing these damaging effects, as it was seen that HRT had some efficacy in maintaining muscle and bone mass, preserving the bone resistance and minimizing some deleterious processes during the menopause. CONCLUSION: Protein restriction has adverse effects on metabolism, leading to more severe menopausal symptoms, and HRT could minimize these effects. Therefore, special attention should be given to a balanced diet during menopause and HRT.Cite this article: Bone Joint Res 2019;8:573-581.

Functioning of active postmenopausal women with osteoporosis / Funcionalidade de mulheres ativas com osteoporose pós-menopausa

Abstract Introduction: The multiple aspects of disability in patients with osteoporosis require comprehensive tool for their assessment. The International Classification of Functioning, Disability and Health (ICF) is designed to describe the experience of such patients with theirs functioning. Objective: This study aimed to describe the functioning in a sample of active postmenopausal women with osteoporosis according to the brief ICF core set for osteoporosis. Methods: This cross-sectional study was conducted among active community-dwelling older adults in a southern Brazilian city. Participants were enrolled by convenience sampling from a group conducting supervised aquatic and land-based exercises. Active postmenopausal women with osteoporosis were included. Thirty-two women (mean age 68.0 ± 5.1 years old) participated in the evaluation. The brief ICF core set for osteoporosis was used to establish functional profiles. The categories were considered valid when ≥20% of participants showed some disability (according to ICF qualifiers). Results: No category showed a high level of disability, as >50% of women rated by qualifiers .3 or .4. Only the category e580 was considered by all participants as a facilitator. Conclusion: The brief ICF core set for osteoporosis results demonstrated that this classification system is representative to describe the functional profile of the sample. Active postmenopausal women with osteoporosis presented few impairments related to body functions and structures, activities and participation and environmental factors.

Resumo Introdução: Os vários aspectos da incapacidade em pacientes com osteoporose requerem uma ferramenta completa para sua avaliação. A Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) considera os múltiplos aspectos da funcionalidade das pessoas. Objetivo: Este estudo objetivou descrever a funcionalidade de uma amostra de mulheres ativas com osteoporose pós-menopausa de acordo com a versão abreviada do core set da CIF para osteoporose. Métodos: Foi realizado um estudo transversal com mulheres com diagnóstico clínico de osteoporose e que participavam regularmente de um grupo de atividade física em solo e hidroginástica. Trinta e duas mulheres (idade média 68,0±5,1 anos) participaram da avaliação. Foi utilizada a versão abreviada do core set da CIF para osteoporose para estabelecer o perfil funcional da amostra. As categorias do core set foram consideradas válidas se ao menos 20% da amostra apresentassem algum grau de incapacidade (de acordo com os qualificadores da CIF). Resultados: Nenhuma categoria mostrou um alto grau de deficiência (>50% da amostra com qualificadores .3 ou .4). Apenas a categoria e380 foi considerada por todas as participantes como um facilitador. Conclusão: O uso da versão abreviada do core set da CIF para osteoporose demonstrou que este sistema de classificação é representativo para descrever a funcionalidade de mulheres ativas com osteoporose pós-menopausa, as quais apresentavam algumas deficiências relacionadas às funções e estruturas do corpo, atividade e participação e fatores ambientais.

Osteoporose: identificando o risco de fratura / Osteoporosis: targeting the risk of fracture

A osteoporose é a doença do metabolismo ósseo mais comum, afetando cerca de 200 milhões de pessoas em todo o mundo. As fraturas por fragilidade, sua consequência mais temida, são a maior causa da diminuição da qualidade de vida, morbidade e mortalidade feminina na pós-menopausa. Entretanto, identificar as mulheres com risco de fratura e que beneficia -se-ão do tratamento farmacológico é desafiado . Metodologias de seleção são falhas, sendo intenso o debate atual sobre o tratamento excessivo versus deficien e. A definição da probabilidade de fratura em termos absolutos, utilizando fatores de risco clínicos e avaliação da densidade óssea, com auxílio de ferramentas clínicas, é a forma utilizada atualmente na seleção de indivíduos para tratamento. O ginecologista precisa conhecer e dominar esta abordagem para realizar uma boa assistência a mulheres com osteoporose.

Osteoporosis is the most common disease of bone metabolism, affecting approximately 200 million people worldwide. The fragility fractures, his most feared consequence, are a major cause of decreased quality of life, morbidity and mortality in postmenopausal women. However, identifying women with high risk of fracture which will benefit from pharmacological treatment is challenging. Screening methodologies are not accurate leading to an intense debate about over versus sub treatment. Acquiring probability of fracture, using clinical risk factors and bone mass, with clinical tools assistance, is the best way to select individuals for treatment. The gynecologist must know and master this approach to make a good assistance to women with osteoporosis.

Evaluación de la respuesta densitométrica en pacientes con osteoporosis posmenopáusica tratadas con ranelato de estroncio o denosumab / Densitometric response in postmenopausal osteoporosis treated with strontium ranelate or denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr. (AU)

Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of "responders" was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR. (AU)

Publicaciones de artículos originales de autores cubanos sobre algunas afecciones endocrinas en la mujer de edad mediana / Publication of original papers on some endocrine illnesses in middle-aged women by Cuban authors

Introducción: en la posmenopausia se incrementa la morbilidad por afecciones endocrinas, cuya frecuencia varía en las diferentes regiones del mundo y que desconocemos en nuestro medio. Objetivo: identificar la frecuencia que en artículos originales autores cubanos hacen referencia sobre afecciones endocrinas frecuentes en la edad mediana de la mujer cubana, y reportar los artículos útiles. Métodos: estudio infométrico referido a las publicaciones de autores cubanos recuperados de las bases de datos (Lilacs, Medicc Review, Esbco, PubMed, Cochrane Library, Scielo Cuba y Cumed), repositorios de tesis, eventos médicos nacionales, relacionados con la osteoporosis posmenopausia, la diabetes mellitus tipo 2, el nódulo del tiroides, el hipo e hipertiroidismo y la tiroiditis autoinmune. Se incluyeron los artículos originales reportados entre 1995-2012, accesibles, con referencia a mujeres con edades 40-59 años, y en los que se especificara la metodología utilizada para establecer los diagnósticos de referencia. Resultados: se identificaron 7 703 trabajos que incluían al menos uno de los descriptores definidos. El 2,4 por ciento de los reportes de autores cubanos fueron útiles, y en todos se identificó una alta frecuencia de las afecciones referidas. La dificultad en el acceso virtual e impreso fue la principal causa de no utilidad de los artículos. Conclusiones: se evidencia la poca frecuencia o visibilidad de la morbilidad por afecciones endocrinas en la mujer de edad mediana(AU)

Introduction: in the postmenopausal period, morbidity from endocrine illnesses increases and their frequency varies in different parts of the world, but knowledge about this topic is limited in our country. Objective: to determine the frequency of reference to common endocrine illnesses affecting Cuban middle-aged women in original papers by Cuban authors and to report on useful articles. Methods: informative study of the publication of Cuban papers retrieved in Lilacs, Medicc Review, Esbco, PubMed, Cochrane Library, Scielo Cuba and Cumed databases, thesis repositories and national medical events, which cover postmenopausal osteoporosis, type 2 diabetes mellitus, thyroid modes, hypo and hyperthyroidism and autoimmune thyroiditis. It included accessible original papers from the 1995 to 2012 period, making reference to 40-59 years-old women and specifying the used methodology to make diagnoses. Results: there were found 7 703 papers that comprised at least one of the defined subject headings. In the group, 2.4 percent of reports by Cuban authors were useful and all identified high frequency of the above-mentioned illnesses. The extent of difficulties in having access, either digital or printed, to these articles was the main cause of classifying them as useless. Conclusions: low frequency of visibility of morbidity from endocrine illnesses in the Cuban middle-aged women was demonstrated(AU)

Efeitos combinados do ácido zoledrônico e do propranolol sobre a densidade óssea e marcadores bioquímicos de remodelação óssea em ratas osteopênicas submetidas à ovariectomia / Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats

Objetivos: Este estudo foi desenvolvido para investigar a eficácia e a segurança do ácidozoledrônico (ZOL) e do propranolol (PRO) como monoterapia e terapia combinada em ummodelo de rato com osteoporose pós-menopáusica. Métodos: Ratas Wistar fêmeas foram ovariectomizadas (OVX) ou submetidas à cirurgia simulada (placebo) aos três meses de idade. Doze semanas depois da cirurgia, as ratas foram divididas em seis grupos: (1) placebo + veículo; (2) OVX + veículo; (3) OVX + ZOL (100 µg/kg, dose única intravenosa); (4) OVX + ZOL (50 µg/kg, dose única intravenosa); (5) OVX + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana); (6) OVX + ZOL (50 µg/kg, dose única intravenosa) + PRO (0,1 mg/kg, via subcutânea, cinco dias por semana) durante 12 semanas. Depois do tratamento, testou-se a densidade óssea, a porosidade e a microarquitetura tra-becular dos fêmures. Também foram avaliados marcadores bioquímicos séricos e urinários. Resultados: A terapia combinada com ZOL mais PRO foi mais eficaz em corrigir a diminuição do cálcio sérico e o aumento do nível sérico de fosfatase alcalina e fosfatase ácida resistenteao tartarato do que a monoterapia com ZOL ou PRO. Além disso, a terapia combinada comZOL mais PRO foi mais eficaz em corrigir o aumento dos níveis urinários de cálcio, fósforo ecreatinina do que a monoterapia com ZOL ou PRO. A terapia combinada com ZOL mais PRO também preservou a microarquitetura trabecular e a porosidade do osso cortical. Conclusão: Os resultados sugerem que a terapia combinada com ZOL mais PRO pode ser aabordagem mais eficaz para o tratamento da osteoporose grave em humanos. .

Objectives: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. Methods: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months ofage. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 뀅g/kg, i.v. single dose); (4) OVX + ZOL (50 뀅g/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 뀅g/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. Results: Combined treatment with ZOL plus PRO corrected the decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected the increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. Conclusion: These data suggest that combined treatment with ZOL plus PRO could be a more effective approach for treating severe osteoporosis in humans. .

Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats.

OBJECTIVES: The present study was designed to investigate further the efficacy and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and combination therapy in a rat model of postmenopausal osteoporosis. METHODS: Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post-surgery, rats were randomized into six groups: (1) sham + vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 µg/kg, i.v. single dose); (4) OVX + ZOL (50 µg/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per week); (6) OVX + ZOL (50 µg/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days per week) for 12 weeks. After treatment, femurs were tested for bone density, porosity and trabecular micro-architecture. Biochemical markers in serum and urine were also determined. RESULTS: Combined treatment with ZOL plus PRO corrected decrease in serum calcium and increase in serum alkaline phosphatase and tartarate resistant acid phosphatase level better than single-drug therapy using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected increase in urine calcium, phosphorous and creatinine level better than single-drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also preserved the trabecular micro-architecture and cortical bone porosity. CONCLUSION: These data suggest that combined treatment with ZOL plus PRO could be more effective approach for treating severe osteoporosis in humans.

Cost-minimization study comparing annual infusion of zoledronic acid or weekly oral alendronate in women with low bone mineral density.

Cost-minimization study to assess the annual direct costs of 2 antiresorptive strategies in postmenopausal women with low bone mineral densities (BMDs). Patients were randomly assigned to receive 70 mg of oral weekly alendronate or a 1-time 5mg of intravenous zoledronic acid. All medical and nonmedical direct costs were recorded for 1 yr. Student's t-test or the Chi-squared test was used. A total of 101 postmenopausal women were enrolled with a mean age of 58.3 ± 7.6 yr and a postmenopausal period of 13.5 ± 8.3 yr. A total of 50 patients completed 1 yr of alendronate and 51 patients received zoledronic acid. At baseline, no differences were seen between the 2 groups in anthropometric measures, comorbidities, and bone mineral density. The costs for medical attention for low bone mass were $81,532 (US Dollars) for the alendronate group and $69,251 for the zoledronic acid group; the cost per patient was $1631 in the alendronate group vs $1358 in the zoledronic acid group (p<0.0001). Therefore, zoledronic acid treatment provided an annual savings of 15% of the direct costs compared with oral alendronate treatment. Moreover, there was a significant increase in lumbar spine T-scores in the zoledronic acid group when compared with the alendronate group. Annual zoledronic acid infusion as an antiresorptive treatment in women with low BMD provides significant monetary savings when compared with weekly alendronate therapy for 1 yr. Zoledronic acid infusion is also linked to higher increase in BMD and compliance.

Costos de fracturas en mujeres con osteoporosis en Colombia / Costs of fractures in women with osteoporosis in Colombia

Resumen Introducción: la osteoporosis posmenopáusica (OPM) es una enfermedad que reduce la densidad yla calidad de los huesos, aumentando el riesgo de sufrir fracturas. En Colombia no existe información documentada sobre los costos, ni las frecuencias de uso de recursos para el diagnóstico y tratamiento de la OPM y las fracturas asociadas. Material y métodos: se realizó un consenso con 11 expertos, mediante una metodología Delphi modificada, se aplicaron los costos utilizando el manual tarifario ISS 2001, finalmente, se estimó para 2015 qué impacto económico tendría para el país el tratamiento de las fracturas de cadera, vertebrales y de radio distal. Resultados: el costo de diagnosticar y seguir adecuadamente a una paciente con OPM por un año, es de aproximadamente $622.588,15; el costo en el momento de presentarse una fractura de cadera que requiera manejo quirúrgico, es $8.687.829,21, el costo de manejar quirúrgicamente una fractura vertebral y de radio distal es $11.348.379,90 y $2.319.111,67 respectivamente. Los pacientes con fractura vertebral que no requieren manejo quirúrgico pueden costar $5.034.055,60 en un año de seguimiento. Para el 2015 el impacto económico de tratar las fracturas de cadera en el país sería de $205.602.914.414, para las vertebrales con manejo quirúrgico sería de $1.370.947.862, y con manejo no quirúrgico sería de $11.653.771.426 y para las fracturas de radio distal sería de $122.858.360.231. Conclusiones: Se hace evidente la necesidad de priorizar la enfermedad, gestionar los riesgos asociados a sus complicaciones y darle el manejo de una patología de alto impacto en la salud pública. (Acta Med Colomb 2014; 39: 46-56).

Abstract Introduction: postmenopausal osteoporosis (PMO) is a disease that reduces the density and quality of bones, increasing the risk of fractures. In Colombia there is no documented information on the costs and frequency of use of resources for the diagnosis and treatment of OPM and associated fractures. Materials and methods: a consensus with 11 experts was conducted using a Delphi modified methodology. Costs were applied using the tariff handbook ISS 2001 and in the end was estimated what economic impact would have in 2015 for the country the treatment of hip vertebral and distal radius fractures. Results: the cost to diagnose and properly follow a patient with PMO for one year is approximately $622,588.15. The cost at the time of a hip fracture that requires surgical management is $8,687,829.21. The cost of surgical management of a spinal fracture and distal radius is $11,348,379.90 and $2,319,111.67 respectively. Patients with spinal fractures that do not require surgical management can cost $5,034,055.60 in a one year follow up. By 2015, the economic impact of treating hip fractures in the country would be $205,602,914,414, for vertebral fractures with surgical management would be $1,370,947,862, and non-surgical management would be $11,653,771,426 and for distal radius fractures it would be $122,858,360,231. Conclusions: the need to prioritize the disease, manage the risks associated with its complications and offer the management of a pathology of high impact on public health, is evident. (Acta Med Colomb 2014; 39: 46-56).

Osteoporosis posmenopáusica: calidad de vida

Objetivo: Evaluar la calidad de vida en pacientes con osteoporosis posmenopáusica, comparando con un grupo de posmenopáusica sin osteoporosis. Métodos: Se incluyeron 112 pacientes con diagnóstico de osteoporosis posmenopáusica, comparado con 112 pacientes posmenopáusicas sin osteoporosis. Fueron excluidas pacientes con diagnóstico previo de patología psiquiátrica o que recibieran tratamiento hormonal, quimioterapia o radioterapia. Para recabar los datos se utilizó un instrumento validado internacionalmente (QUALEFFO-41) y se analizaron los resultados según el algoritmo especial para dicho instrumento, expresándose en media y desviación estándar las variables continuas, y las nominales en frecuencia y porcentajes. Resultados: El promedio de edad de las pacientes con osteoporosis fue de 60 ± 7 años y el de las mujeres sin osteoporosis fue de 57 ± 6 años (P=0,000). Al comparar grupos estudio y control se encontró diferencias estadísticamente significativas en la función física (P=0,000), quehaceres domésticos (P=0,000) y movilidad (P=0,001), El puntaje total del instrumento tuvo diferencia significativa (P=0,000). No hubo diferencias significativas en el puntaje en cuanto a actividades sociales y de tiempo libre, percepción de la salud general y función mental. Conclusión: Las pacientes con osteoporosis posmenopáusica tienen peor calidad de vida que las posmenopáusicas sin osteoporosis.

Objective: To evaluate the quality of life in patients with postmenopausal osteoporosis, compared to a group of postmenopausal women without osteoporosis. Methods: We included 112 patients with diagnosis of postmenopausal osteoporosis, compared with 112 patients postmenopausal women without osteoporosis. Patients with diagnosis of psychiatric pathology were excluded or who received hormone therapy, chemotherapy, or radiation therapy. To collect the data we used a validated instrument internationally (QUALEFFO-41) and analyzed the results according to the special algorithm for that instrument, expressed in average and standard deviation for continuous variables, and the nominal frequency and percentages. Results: The average age of patients with osteoporosis was 60 ± 7 years and that of women without osteoporosis was 57 ± 6 years (P= 0.000). Comparing both groups, was found statistically significant differences in physical function (P= 0.000), housework (P = 0.000) and mobility (P= 0.001), the total score of the instrument had significant difference (P= 0.000). There was no significant difference in score in terms of social activities and free time, perception of the general health and mental function. Conclusion: Patients with postmenopausal osteoporosis have poorer quality of life than the postmenopausal osteoporosis without it.

Factores de riesgo para osteoporosis en mujeres posmenopáusicas de Guadalajara, Jalisco / Risk factors for osteoporosis in postmenopausal women from Guadalajara, Jalisco

Objetivo. Conocer los factores de riesgo y la frecuencia de osteoporosis (OP) en mujeres posmenopáusicas. Material y métodos. Se midió la densidad mineral ósea de columna en 513 mujeres posmenopáusicas de un hospital de Guadalajara, Jalisco durante 2007-2008. Los puntos de corte de las variables asociadas se obtuvieron por curvas ROC y la razón de momios (RM) mediante regresión logística. Resultados. El 25.2% (IC95% 21.44-28.96) de las mujeres mostró OP. Las variables asociadas a OP y sus puntos de corte fueron: edad >60 años, peso <71kg, talla <1.54m e IMC <29.2kg/m², con RM mayores a 3.19 (p<0.0001). Conclusiones. Se recomienda establecer puntos de corte para estimar factores de riesgo para OP con mayor precisión en cada población.

Objective. To know risk factors and the frequency of osteoporosis (OP) in postmenopausal women. Materials and methods. Bone mineral density was measured in lumbar spine of 513 postmenopausal women from a hospital of Guadalajara, Jalisco during 2007-2008. The cutoff points of the associated variables were obtained by ROC curves and odds ratio (OR) by logistic regression. Results. The 25.2% (95%CI 21.44-28.96) of the women was OP. The variables associated with OP and cutoff points were age >60 years, weight <71kg, height <1.54m and BMI <29.2kg/m², with OR greater than 3.19 (p<0.0001). Conclusions. It is recommended setting cutoff points to estimate risk factors for OP more accurately in each population.

Necesidad de tratamiento periodontal en relación al consumo de alendronato en pacientes con osteoporosis posmenopáusica / Need for periodontal treatment in relation to consumption of alendronate in patients with postmenopausal osteoporosis

Objetivo: Determinar si existe relación entre tiempo de tratamiento con alendronato y necesidad de tratamiento periodontal en pacientes con osteoporosis posmenopáusica. Pacientes y Métodos: El estudio de corte transversal, descriptivo y observacional, incluyó un total de 112 pacientes con osteoporosis posmenopáusica atendidas en los Servicios de Gineco-Obstetricia o Reumatología del Hospital Belén de Trujillo, a las que se les realizó un examen clínico para determinar la necesidad de tratamiento periodontal y se registró el inicio de tratamiento con alendronato, según la historia clínica. Resultados: Se encontró relación significativa inversa entre tiempo de tratamiento con alendronato y necesidad de tratamiento periodontal en pacientes con osteoporosis posmenopáusica (p<0.05 y r=-0.533). Además, el 84.1 por ciento de pacientes presentó más de 6 meses de consumo de alendronato y el código 2 del Índice de Necesidad de Tratamiento Periodontal en la Comunidad fue el más frecuente para esta población. Conclusión: Los resultados permiten concluir que existe relación inversa entre tiempo de tratamiento con alendronato y necesidad de tratamiento periodontal en pacientes con osteoporosis posmenopáusica. Recomendación: Se recomienda realizar investigaciones sobre la utilidad que podría tener el alendronato como coadyuvante en el tratamiento de la enfermedad periodontal en mujeres con osteoporosis posmenopáusica.

Objective: To determine the correlation between the duration of alendronate’s treatment and the need for periodontal treatment in patients with postmenopausal osteoporosis. Patients and Methods: This cross-sectional, descriptive and observational study included a total of 112 patients with postmenopausal osteoporosis treated in Gyneco-Obstetric or Rheumatology Services at Hospital Belén de Trujillo, who underwent a clinical examination to determine the need for periodontal treatment. The start of the treatment with alendronate was registered, according to medical records. Results: We found significant inverse relationship between treatment duration with alendronate and periodontal treatment need in patients with postmenopausal osteoporosis (p<0.05 and r=-0.533). In addition, 84.1 percent of patients had more than 6 months of alendronate consumption and code 2 Community Periodontal Index of Need for Periodontal Treatment was the most frequent in this population. Conclusion: The results suggest that there is an inverse relationship between treatment duration with alendronate and periodontal treatment needs in patients with postmenopausal osteoporosis. Recommendation: it is suggested to carry out research about the utility that alendronate could have as an adjunct in the treatment of periodontal disease in women with postmenopausal osteoporosis.