Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study.

A Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (mu FEA), over 2 years, in postmenopausal osteoporotic women.Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.Results In the intention-to-treat population (n = 83, age: 64 +/- 8 years; lumbar T-score: -2.8 +/- 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (-0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

A retrospective case-control study assessing the role of trabecular bone score in postmenopausal Caucasian women with osteopenia: analyzing the odds of vertebral fracture.

This case-control study assessed whether the trabecular bone score (TBS), determined from gray-level analysis of DXA images, might be of any diagnostic value, either alone or combined with bone mineral density (BMD), in the assessment of vertebral fracture risk among postmenopausal women with osteopenia. Of 243 postmenopausal Caucasian women, 50-80 years old, with BMD T-scores between -1.0 and -2.5, we identified 81 with osteoporosis-related vertebral fractures and compared them with 162 age-matched controls without fractures. Primary outcomes were BMD and TBS. For BMD, each incremental decrease in BMD was associated with an OR = 1.54 (95% CI = 1.17-2.03), and the AUC was 0.614 (0.550-0.676). For TBS, corresponding values were 2.53 (1.82-3.53) and 0.721 (0.660-0.777). The difference in the AUC for TBS vs. BMD was statistically significant (p = 0.020). The OR for (TBS + BMD) was 2.54 (1.86-3.47) and the AUC 0.732 (0.672-0.787). In conclusion, the TBS warrants a closer look to see whether it may be of clinical usefulness in the determination of fracture risk in postmenopausal osteopenic women.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

Adhésion thérapeutique et maladies chroniques: l'exemple de l'ostéoporose [Adherence and chronic disease: what's about osteoporosis].

Osteoporosis is a silent chronic disease. The human, medical and economic impacts, as well as the easy access to the screening and specific treatments incite us to introduce a treatment as soon as this one is justified. The maximal efficiency of treatments is possible only if the therapeutic adherence (which includes compliance and persistence) is good. Regrettably, as frequently in the chronic diseases, this one is often bad. It can be strengthened by a better patient's education and information, a better follow-up, but also by a today available variety of treatments.

Impact de la prophylaxie hormonale sur les fractures du fémur proximal des femmes postménopausiques: une étude de simulation. [Impact of hormonal prevention on fractures of the proximal femur in postmenopausal women: a simulation study].

A simulation model of the effects of hormone replacement therapy (HRT) on hip fractures and their consequences is based on a population of 100,000 post-menopausal women. This cohort is confronted with literature derived probabilities of cancers (endometrium or breast, which are contra-indications to HRT), hip fracture, disability requiring nursing home or home care, and death. Administration of HRT for life prevents 55,5% of hip fractures, 22,6% of years with home care and 4,4% of years in nursing homes. If HRT is administered for 15 years, these results are 15,5%, 10% and 2,2%, respectively. A slight gain in life expectancy is observed for both durations of HRT. The net financial loss in the simulated population is 222 million Swiss Francs (cost/benefit ratio 1.25) for lifelong administration of HRT, and 153 million Swiss Francs (cost/benefit ratio 1.42) if HRT is administered during 15 years.

The role of teriparatide in sequential and combination therapy of osteoporosis.

Osteoporosis is complicated by the occurrence of fragility fractures. Over past years, various treatment options have become available, mostly potent antiresorptive agents such as bisphosphonates and denosumab. However, antiresorptive therapy cannot fully and rapidly restore bone mass and structure that has been lost because of increased remodelling. Alternatively recombinant human parathyroid hormone (rhPTH) analogues do increase the formation of new bone material. The bone formation stimulated by intermittent PTH analogues not only increases bone mineral density (BMD) and bone mass but also improves the microarchitecture of the skeleton, thereby reducing incidence of vertebral and nonvertebral fractures. Teriparatide, a recombinant human PTH fragment available in Switzerland, is reimbursed as second-line treatment in postmenopausal women and men with increased fracture risk, specifically in patients with incident fractures under antiresorptive therapy or patients with glucocorticoid-induced osteoporosis and intolerance to antiresorptives. This position paper focuses on practical aspects in the management of patients on teriparatide treatment. Potential first-line indications for osteoanabolic treatment as well as the benefits and limitations of sequential and combination therapy with antiresorptive drugs are discussed.

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.

Radio 33 comparado con el patrón de oro para diagnóstico de osteoporosis

Introducción: la medición de la densidad mineral ósea en el fémur y columna lumbar es considerada la prueba de oro para el diagnóstico de osteoporosis en mujeres postmenopáusicas, sin tener suficiente evidencia de la utilidad al medir de manera individual o simultanea el radio 33 con este mismo propósito. Metodología Se realizó un estudio de pruebas diagnósticas, valorando concordancia anidada para determinar el valor diagnóstico del radio 33 comparado con los resultados por dual fémur y columna, actualmente patrón de oro el en diagnóstico. Se incluyeron mujeres mayores de 50 años entre el periodo de 2008 y 2011. Resultados Se incluyeron 3241 osteodensitometrias de pacientes femeninas con columna AP, dual fémur, radio ultradistal y radio 33. Tomando como estándar de oro la medición en columna y/o femur, el radio-33 obtuvo una sensibilidad de 95.5% y especificidad de 91% (p= 0,000) para osteoporosis, y una sensibilidad de 76.5% y especificidad de 54.9% p=0,000 para el diagnóstico de osteopenia. El radio 33 permite diagnosticar un 35% adicional de casos que no son captados con la medición en fémur y columna lumbar. Discusión La osteodensitometría en los sitios usados comúnmente, predice únicamente el 40% del riesgo de fractura (1). Si se incluye la medición de radio 33, la sensibilidad de la osteodensitometría sube en un 35.66% adicional, logrando detectar más pacientes con este riesgo y generando un impacto en la oportunidad del tratamiento y quizás reducción en la morbi-mortalidad secundaria a fracturas en esta población susceptible.

Association between dietary phyto-oestrogens and bone density in men and postmenopausal women

Phyto-oestrogens have been associated with a decreased risk for osteoporosis, but results from intervention and observational studies in Western countries have been inconsistent. In the present study, we investigated the association between habitual phyto-oestrogen intake and broadband ultrasound attenuation (BUA) of the calcanaeum as a marker of bone density. We collected 7 d records of diet, medical history and demographic and anthropometric data from participants (aged 45–75 years) in the European Prospective Investigation into Cancer-Norfolk study. Phyto-oestrogen (biochanin A, daidzein, formononetin; genistein, glycitein; matairesinol; secoisolariciresinol; enterolactone; equol) intake was determined using a newly developed food composition database. Bone density was assessed using BUA of the calcanaeum. Associations between bone density and phyto-oestrogen intake were investigated in 2580 postmenopausal women who were not on hormone replacement therapy and 4973 men. Median intake of total phyto-oestrogens was 876 (interquartile range 412) μg/d in postmenopausal women and 1212 (interquartile range 604) μg/d in men. The non-soya isoflavones formononetin and biochanin A were marginally significant or significantly associated with BUA in postmenopausal women (β = 1·2; P < 0·1) and men (β = 1·2; P < 0·05), respectively; enterolignans and equol were positively associated with bone density in postmenopausal women, but this association became non-significant when dietary Ca was added to the model. In the lowest quintile of Ca intake, soya isoflavones were positively associated with bone density in postmenopausal women (β = 1·4; P < 0·1). The present results therefore suggest that non-soya isoflavones are associated with bone density independent of Ca, whereas the association with soya or soya isoflavones is affected by dietary Ca.

Influence of body composition on bone mass in postmenopausal osteoporotic women

We aimed at evaluating the relationship of lean and fat mass to bone mass in osteoporotic postmenopausal women. We invited 65 women who were being treated at the Sao Paulo Hospital osteoporosis outpatients` clinic to participate. Body composition and bone mineral density (BMD) measurements were performed using Dual-energy X-ray absorptiometry methodology (DXA). The mean age and weight were 69.7 +/- 6.4 years and 56.3 +/- 7.6 kg, respectively. Accordingly to the body mass index (BMI), 52.8% were of normal weight and 47.1% of the patients were overweight. Overweight women had significantly higher bone mass. Similarly, skeletal muscle index (SMI) showed a positive effect on BMD measurements and women with sarcopenia had significantly lower BMD measurements in total femur and femoral neck. In multiple regression analysis only lean mass and age, after adjustments to fat mass and BMI, were able to predict total body bone mineral content (BMC) (R(2) = 28%). Also lean mass adjusted to age and BMI were able to predict femoral neck BMD (R(2) = 14%). On the other hand, none of the components of the body composition (lean mass or fat mass) contributed significantly to explaining total femur BMD and neither body composition measurements were associated with spine BMD. These findings suggest that lean mass has a relevant role in BMC and BMD measurements. In addition, lower BMI and lean mass loss (sarcopenia) is associated to lower BMC and BMD of femoral neck and total femur and possible higher risk of osteoporotic fracture. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS)

The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.

Effect of raloxifene on the vaginal epithelium of postmenopausal women

Objective: The objective was to analyze the effect of raloxifene oil the vaginal epithelium of postmenopausal women.Study design: In this non-randomized clinical trial, 80 women (mean age = 60.6 years) were prospectively studied. Forty patients received 60 mg/day of raloxifene (RG), and 40 women constituted it non-treated control group (CG), paired by age and time since menopause. The treated group consisted of patients with osteoporosis of the lumbar spine. Those with a diagnosis of infection ill the lower genital tract and using hormone therapy (HT) up to 6 months prior to the study were excluded. Vaginal smears were collected at baseline and after 6 months of intervention. The vaginal maturation value (VMV) was determined, and counts of superficial, intermediate and parabasal cells were performed. Smears were analyzed by only one cytopathologist who was blinded to patient data. The t-test, Wilcoxon test, and Chi-Squared test were used in the statistical analysis.Results: The study groups were homogeneous regarding age, time since menopause, parity, HT use, smoking, and body mass index. No statistically significant differences were observed in VMV median values (RG, 39.7 and 35.7; CG, 50.0 and 50.0, respectively) or in the percentage of superficial, intermediate and parabasal cells between the groups at baseline and after 6 months (p > 0.05). There was no significant correlation between VMV and age, time since menopause, previous HT use, or body mass index, in either of the groups.Conclusion: Treatment with raloxifene for 6 months has no effect on the maturation of the vaginal epithelium ill postmenopausal women with osteoporosis. (C) 2008 Elsevier B.V. All rights reserved.

Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Factors that contribute to low bone density in postmenopausal women in different Amazonian communities

Background: The aim of this study was to verify socioeconomic differences, nutrition, body balance and quality of life (QoL) in postmenopausal women with low bone mineral density (BMD) in two Amazonian communities. Methods: A total of 42 female volunteers participated in the study. The volunteers were separated into two groups: Villa (n= 20; 53±5.5 years) and City (n= 22; 56±7.9 years). The following evaluation instruments were used: dual energy X-ray absorptiometry (DXA); a socioeconomic questionnaire; a QoL questionnaire; a dietary habits questionnaire; and a balance test. Parametric and nonparametric tests were used. Results: The data showed significant differences in socioeconomic level (Δ%=+15.9%, p=0.000),lumbar spine L2-L4 (Δ%=+0.10%,p=0.007), balance(Δ%=+4.3%,p=0.03)and some important aspects of nutrition, such as the consumption of milk (Δ%=+34%, p=0.01) and alcohol (+14.8%, p=0.0001). These significant differences also contributed to the total QoL score (Δ%=+76.2%, p=0.000) and the majority of the QoL-related functions. Conclusion: This study verified that socioeconomic level, nutritional status, physical activity levels and QoL can influence the BMD of postmenopausal women. The study suggests new strategies for official health organizations to use in order to prevent and treat osteoporosis. In addition, this study can provide an orientation to physical activity, nutrition and medical professionals. © The Author(s), 2011.