Trabecular bone score and quantitative ultrasound measurements in the assessment of bone health in breast cancer survivors assuming aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AIs) represent the first-line adjuvant therapy for hormone receptor-positive breast cancer (BC) women. AIs have been associated with an increased rate of fractures. The aim of our study was to investigate trabecular bone score (TBS) and bone quantitative ultrasound (QUS) measurements as bone quality surrogates in AIs users. METHODS: Sixty postmenopausal BC women starting AIs and forty-two controls (mean age 61.64 ± 8.33 years) were considered. Bone mineral density (BMD) at lumbar spine and femoral neck and TBS were measured by DXA; QUS-derived Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), and Ultrasound Bone Profile Index (UBPI) were assessed at phalangeal site; morphometric vertebral fractures (Vfx) by X-ray, serum bone-specific alkaline phosphatase (BSAP), and C-telopeptide of type 1 collagen (CTX) were also evaluated. RESULTS: After 18 months, changes of TBS vs baseline were significantly different between AIs group and controls [Δ TBS - 2.2% vs - 0.4%, respectively, p = 0.001]. AD-SoS, BTT and UBPI values decreased only in AIs' group (- 3.7%, - 6.45%, -8.5%, vs baseline, respectively, pall < 0.001). 3 Vfx occurred in AIs users and were associated with the greater TBS and AD-SoS modifications. In the AIs' group, ΔTBS was associated with ΔAD-SoS (r = 0.58, p < 0.001) and ΔUBPI (r = 0.415, p = 0.001), but not with ΔBMD. Moreover, ΔTBS was independently predicted by ΔAD-SoS, after correcting for BMD, CTX and BSAP level changes (ß = 0.37, SE = 2.44, p < 0.001). CONCLUSIONS: TBS and phalangeal QUS provide useful information related to bone quality in AI-treated BC survivors and could be considered for fracture risk evaluation.

Cost-effectiveness of implementing guidelines for the treatment of glucocorticoid-induced osteoporosis in Japan.

A model-based cost-effectiveness analysis was performed to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO). The treatment indication for GIO in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture. INTRODUCTION: The purpose of this study was to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO) from the perspective of the Japanese healthcare system. METHODS: A patient-level state transition model was developed to predict lifetime costs and quality-adjusted life years (QALYs) in postmenopausal Japanese women with osteopenia or osteoporosis using glucocorticoid (GC). An annual discount rate of 2% for both costs and QALYs was applied. The incremental cost-effectiveness ratio (ICER) of 5-year alendronate therapy compared with no therapy was estimated with different combinations of the risk factors such as starting age (45, 55, or 65), femoral neck BMD (% young adult mean (YAM) of 70%, 75%, or 80%), dose of GC (2.5, 5, or 10 mg per day), and the presence of previous fracture (yes or no). RESULTS: For 55-year-old women using GC with a BMD of 75% of YAM, the ICER ranged from $10,958 to $ 29,727 per QALY. Scenario analyses indicated that the lower age, the lower BMD, the higher dose of GC, and the presence of previous fracture associated with lower ICER. The best-case scenario was 45-year-old women with a BMD of 70% of YAM, GC dose of 10 mg per day, and previous fracture, and resulted in healthcare cost-savings. The worst-case scenario was 65-year-old women with a BMD of 80% of YAM, GC dose of 2.5 mg per day, and no previous fracture, and resulted in the ICER of $66,791 per QALY. Sensitivity analyses in the worst-case scenario showed that the annual discount rate for costs and health benefit had the strong influence on the estimated ICER. Although the ICER was influenced by other parameters such as disutility due to vertebral fracture, efficacy of alendronate, and so on, the ICERs remained more than $50,000 per QALY. CONCLUSIONS: The cost-effectiveness of preventive alendronate therapy for postmenopausal women with osteopenia or osteoporosis using GC is sensitive to age, BMD, GC dose, and the presence of previous fracture. Our analysis suggested that the treatment indication for postmenopausal women with osteopenia or osteoporosis using GC in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture.

Hormone therapy and osteoporosis in breast cancer survivors: assessment of risk and adherence to screening recommendations.

The long-term impact of hormone therapy for breast cancer on risk of osteoporosis and the extent to which bone screening recommendations are implemented in daily practice remain unknown. We found that the aromatase inhibitor-induced risk of osteoporosis did not continue in the off-treatment follow-up. Adherence to screening recommendations was suboptimal. INTRODUCTION: A case-cohort study was undertaken to better understand the impact of hormone therapy on breast cancer patients' risk of osteoporosis, and to estimate the extent to which current bone mineral density screening recommendations are implemented in real-life daily practice. METHODS: This study is based on 1692 female breast cancer survivors recruited from "Leumit" healthcare fund, who were diagnosed with primary nonmetastatic invasive breast cancer between 2002 and 2012. A 20% random subcohort was sampled at baseline, and all osteoporosis cases were identified. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated by weighted Cox proportional hazards models. RESULTS: Of 1692 breast cancer survivors, 312 developed osteoporosis during a median follow-up of 5 years. The crude cumulative incidence of osteoporosis accounting for death as a competing risk was 25.7% (95% CI, 21.9-29.5%). In multivariable analyses, osteoporosis was positively associated with the aromatase inhibitor (AI) sequential treatment after tamoxifen (HR, 3.14; 95% CI, 1.44-6.88; P = .004) but was more pronounced with AI use as upfront monotherapy (HR, 5.53; 95% CI, 1.46-20.88; P = .012). This effect did not continue in the off-treatment follow-up. In subgroup analysis by menopausal status, tamoxifen did not seem to confer a protective effect on bone health in postmenopausal patients. Adherence to screening recommendations in AI-treated postmenopausal women was suboptimal, particularly at baseline and after 48 months of continuous AI use. CONCLUSIONS: The natural, age-related reduction in bone density is exacerbated by breast cancer active AI treatment. Future research should focus on investigating screening adherence-related barriers/facilitators and effective strategies to bring practice in line with agreed standards.

SERMs: meeting the promise of multifunctional medicines.

The successful development and clinical evaluation of the selective estrogen receptor modulators in the Study of Tamoxifen and Raloxifene trial provides an occasion to reflect on the milestone that has been achieved and the potential for further progress in the chemoprevention of breast cancer. The evolution of tamoxifen from a successful treatment for breast cancer to the first chemopreventive for any cancer took two decades. Clinicians gained an enormous amount of experience with the use of tamoxifen as a treatment, and, as a result, there were few surprises in terms of efficacy or the side effect profile when the medicine was used to prevent breast cancer in high-risk women. In contrast, raloxifene emerged via the novel path of the evidence-based hypothesis that a drug targeted at one disease, osteoporosis, could also prevent breast cancer. Changes in health care strategies to implement chemoprevention take time, but the evidence now suggests that chemoprevention has become a reality in clinical practice.

Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis.

OBJECTIVES: To determine whether strategies can be devised for the assessment and treatment of glucocorticoid-induced osteoporosis (GIO). DATA SOURCES: Electronic databases were searched up to October 2002. REVIEW METHODS: A systematic review of interventions was undertaken of all randomised controlled trials in which fracture was measured as an outcome. Effectiveness was compared with effectiveness in postmenopausal osteoporosis. The risk of osteoporotic fractures at any given T-score for bone mineral density (BMD) was determined from published meta-analyses of the relationship between BMD and fracture risk. The risk of an osteoporotic fracture in the presence of a prior osteoporotic fracture was computed from a published meta-analysis of the relationship between the prior occurrence of fracture of each type and the risk of a future fracture of each type. The additional risk due to exposure to glucocorticoids was determined by meta-analysis of prospectively studied population-based cohorts. The consequences of fracture on mortality were assessed for each fracture type. Costs and utilities were determined for osteoporosis in the UK by updating systematic reviews of the literature. A model was prepared that comprised an individual patient-based approach that simulated whether or not events occurred in each subsequent year for each patient. Effectiveness was populated from a systematic review of interventions in GIO and postmenopausal osteoporosis. Treatments were given for 5 years using a 5-year offset time (in this context, offset time is the duration for which an effect on fracture persists after the treatment stops). The analytic framework was set at 10 years. Because of the many uncertainties, extensive sensitivity analysis was undertaken. RESULTS: Evidence of anti-fracture efficacy was confined to a minority of agents used in the management of GIO. Only risedronate (a bisphosphonate) and calcidiol (vitamin D) were shown to have significant effects on vertebral fracture risk, but neither had significant effects on non-vertebral fracture risk. In further meta-analyses, the effects of bisphosphonates in GIO were compared with effects combining all available data for bisphosphonates in GIO and in postmenopausal osteoporosis. Since calcidiol is not licensed for use in the UK, cost-effectiveness analysis was confined to risedronate and to a pooled bisphosphonate effect. Analysis of cost-effectiveness of risedronate using the empirical data in GIO showed better cost-effectiveness with increasing age, but at no age did cost-effectiveness ratios fall below the threshold value of 30,000 pounds per quality-adjusted life-year gained. When account was taken of BMD, cost-effectiveness was confined to less than 10% of patients with very low T-scores for BMD. Assuming that bisphosphonate efficacy on fracture risk was comparable to that observed with bisphosphonates in postmenopausal osteoporosis, cost-effectiveness was shown in patients with a prior fracture. In patients with no prior fracture, cost-effectiveness was observed in individuals aged 75 years or more. In younger patients without a prior fracture, cost-effective scenarios were found contingent upon a T-score for BMD that was 2.0 SD or less. CONCLUSIONS: Cost-effective scenarios for risedronate in the management of GIO were identified, but only at the extremes of age and T-score, such that less than 10% of patients aged 50 years or more would be eligible for treatment. Greater cost-effectiveness was observed assuming that the effects of bisphosphonate in GIO were similar to those observed in postmenopausal osteoporosis, an assumption tested by meta-analysis. An assessment algorithm is proposed based on age, the presence of a prior fragility fracture and BMD tests in individuals aged 50 years or more with no fracture. The conclusions derived are conservative, mainly because of the assumptions that were made in the absence of sufficient data. Thus, conclusions that treatment scenarios are cost-effective are reasonably secure. By contrast, scenarios shown not to be cost-effective are less secure. As information in these areas becomes available, the implications for cost-effectiveness of interventions should be reappraised. Health economic assessment based on probability of fracture is an important area for further research. Other areas for further research arise from gaps in empirical knowledge on utilities and side-effects that are amenable to primary research. Further secondary research is recommended to evaluate more closely the impact of all vertebral fractures (rather than clinically overt vertebral fractures) on cost-effectiveness and methods of monitoring treatment.

Valoración de una dieta hipercalórica en el desarrollo de osteoporosis en ratas Sprague-Dawley gonadectomizadas / Hypercalorific diet evaluation in the development of osteoporosis in gonadectomized Sprague-Dawley rats

El trabajo se inició con 34 ratas Sprague-Dawley de siete semanas de edad, de las cuales 26 se sometieron a gonadectomía bilateral para inducirles la menopausia. El grupo control quedó constituido por las restantes 8 ratas no gonadectomizadas. Para evaluar la influencia de la dieta hipercalórica en el desarrollo de osteoporosis, a 13 ratas gonadectomizadas se les suministró una dieta rica en grasa (grupo A), mientras que las otras 13 ratas (grupo B) y el grupo controlk recibieron una dieta regular. Cinco meses después de la ovariectomía, la dieta hipercalórica causó la disminución del contenido de calcio en vértebras lumbares (L3, L4 y L5), mostrándose el efecto de la dieta en cuanto a que, bajo la ingesta de los demás nutrientes, se modificó su utilización, causando una desnutrición generalizada y cooperando así con el proceso de génesis de la osteoporosis. La ovariectomía indujo cambios hormonales que favorecieron el proceso de desmineralización condicionante de osteoporosis, validándose así el modelo experimental