Assessment of bone quality with trabecular bone score in type 2 diabetes mellitus: A study from the FRISBEE cohort.

OBJECTIVE: The purpose of our study was to compare bone mineral density (BMD) and trabecular bone score (TBS) values between patients with type 2 diabetes (T2D) and control subjects with similar FRAX scores in order to evaluate TBS as an additional tool for assessing fracture risk in diabetic subjects. METHODS: A cross-sectional analysis was performed using BMD results from 260 subjects participating in the FRISBEE study (Fracture RISk Brussels Epidemiological Enquiry), an ongoing prospective epidemiological study in a population-based cohort (Brussels, Belgium) of 3560 postmenopausal women aged 60-85 years. TBS measurement was possible in 1108 subjects from the FRISBEE cohort. Among these 1108 subjects, 65 had known T2D at inclusion. For each diabetic case we selected 3 controls from our database. (n = 195). Diabetic subjects and controls were matched for age and baseline FRAX score for major osteoporotic fractures. RESULTS: BMD (g/cm2 ) tended to be higher in T2D than in control subjects, significantly so at the total hip 0.90 ± 0.13 versus 0.87 ± 0.12 (P = 0.015). On the contrary, TBS was significantly lower in the T2D group (mean = 1.19 ± 0.17) compared with the control group (mean = 1.27 ± 0.13) (P = 0.005). Mean TBS remained significantly lower in T2D (1.22 ± 0.17) compared with the control group (1.27 ± 0.13) (P = 0.02) after adjustment for body mass index. CONCLUSION: Our data suggest that TBS complements BMD at the total hip, in demonstrating the "diabetes-associated bone disease".

Effects of Dairy Products Consumption on Health: Benefits and Beliefs--A Commentary from the Belgian Bone Club and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.

Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.

Health state utilities for skeletal-related events secondary to bone metastases.

INTRODUCTION: Patients with bone metastases often experience skeletal-related events (SREs). Although cost-utility models are used to examine treatments for metastatic cancer, limited information is available on utilities of SREs. The purpose of this study was to estimate the disutility of four SREs: spinal cord compression, pathological fracture, radiation to bone, and surgery performed to stabilize a bone. METHODS: General population participants from the UK and Canada completed time trade-off (TTO) interviews to assess the utility of health states drafted based on literature review, clinician interviews, and patient interviews. Respondents first rated a health state describing cancer with bone metastases. Then, the SREs were added to this health state. RESULTS: Interviews were completed with 187 participants (50.8 % male, 80.2 % white). Cancer with bone metastases without an SRE had a mean utility of 0.47 (SD = 0.43) on a standard utility scale (1 = full health, 0 = death). Of the SREs, spinal cord compression was associated with the greatest disutility (i.e., the utility decrease): -0.32 with paralysis and -0.22 without paralysis. Surgery had a disutility of -0.07. Leg, arm, and rib fractures had disutilities of -0.06, -0.04, and -0.03. Two weeks of daily radiation treatment had a disutility of -0.06, while two radiation appointments had the smallest impact on utility (-0.02). CONCLUSION: All SREs were associated with statistically significant utility decreases, suggesting a perceived impact on quality of life beyond the impact of cancer with bone metastases. The resulting disutilities may be used in cost-utility models examining treatments to prevent SREs secondary to bone metastases.

Reducing the burden of bone metastases: current concepts and treatment options.

BACKGROUND: Bone metastases occur frequently in patients with solid tumours such as those of the prostate, breast and lung, and are associated with an increased risk of skeletal-related events (SREs). This article reviews the personal, social and economic burdens of bone metastases and SREs, and approaches to treatment. METHODS: PubMed searches were conducted using a broad range of search terms. Articles identified were refined by author review of abstracts. Additional material was identified by searching recent relevant congress abstracts. RESULTS: Bone metastases often decrease quality of life, but quantitative data on the extent of this effect are limited. Data from the USA demonstrate a significant financial burden associated with bone metastases; similar trends are now being uncovered in Europe as the number of assessments of health economics and healthcare resource utilisation in the region increases. The bisphosphonate zoledronic acid reduces the incidence of SREs compared with placebo. Recent phase 3 studies have shown that therapy with the RANK ligand inhibitor denosumab is superior to zoledronic acid for preventing or delaying SREs in patients with bone metastases from solid tumours. Denosumab also has a comparable safety profile to bisphosphonates, with reduced risk of renal toxicity and acute phase reactions. Data from Europe suggest that denosumab is cost-effective for the prevention of SREs compared with zoledronic acid. Additionally, several new experimental bone-targeted agents show promise. CONCLUSION: Recent progress may help to reshape evidence-based guidelines to improve patient care and reduce the economic burden of bone metastases.

Health technology assessment in osteoporosis.

We review the various aspects of health technology assessment in osteoporosis, including epidemiology and burden of disease, and assessment of the cost-effectiveness of recent advances in the treatment of osteoporosis and the prevention of fracture, in the context of the allocation of health-care resources by decision makers in osteoporosis. This article was prepared on the basis of a symposium held by the Belgian Bone Club and the discussions surrounding that meeting and is based on a review and critical appraisal of the literature. Epidemiological studies confirm the immense burden of osteoporotic fractures for patients and society, with lifetime risks of any fracture of the hip, spine, and forearm of around 40 % for women and 13 % for men. The economic impact is also large; for example, Europe's six largest countries spent €31 billion on osteoporotic fractures in 2010. Moreover, the burden is expected to increase in the future with demographic changes and increasing life expectancy. Recent advances in the management of osteoporosis include novel treatments, better fracture-risk assessment notably via fracture risk algorithms, and improved adherence to medication. Economic evaluation can inform decision makers in health care on the cost-effectiveness of the various interventions. Cost-effectiveness analyses suggest that the recent advances in the prevention and treatment of osteoporosis may constitute an efficient basis for the allocation of scarce health-care resources. In summary, health technology assessment is increasingly used in the field of osteoporosis and could be very useful to help decision makers efficiently allocate health-care resources.

The economic burden associated with skeletal-related events in patients with bone metastases secondary to solid tumors in Belgium.

OBJECTIVES: More than 1.5 million patients worldwide are affected by bone metastases. Patients with bone metastases frequently develop skeletal-related events (SREs, including radiation to bone, non-vertebral fracture, vertebral fracture, surgery to bone, and spinal cord compression) that are associated with high healthcare costs. This study aims to provide an estimate of the cost per SRE in both the inpatient and outpatient settings in Belgian patients with bone metastases secondary to solid tumors (breast, prostate, and lung cancers). METHODS: Patients were retrieved from the IMS Hospital Disease database from 2005-2007. Inclusion was based on the International Classification of Diseases and Related Health Problems Version 9 (ICD-9) diagnosis and/or procedure codes covering patients with breast, prostate, or lung cancer with bone metastases who were hospitalized for one or more SREs. All costs were extrapolated to 2010 using progression in hospitalization costs since 2001. Additional outpatient costs resulting from radiation to bone and diagnostic tests performed in ambulatory settings were estimated by combining published unit costs with resource use data obtained from a Delphi panel. RESULTS: The average cost per SRE across solid tumor types based on the weighted average of inpatient and outpatient costs was €2653 for radiation to bone, €5015 for a vertebral fracture, and €7087 for a non-vertebral fracture. Costs were €12,885 and €15,267 for surgery to bone and spinal cord compression, respectively. LIMITATIONS: No patient follow-up across calendar years could be done. Also, details regarding the exact anatomic sites of SREs were not always available. CONCLUSIONS: SREs add a substantial cost to the management of patients with bone metastases. Avoiding SREs can lead to important cost-savings for the healthcare payer.

Assessment of circulating Dickkopf-1 with a new two-site immunoassay in healthy subjects and women with breast cancer and bone metastases.

The aim of our study was to investigate the sex- and age-related changes of serum Dickkopf-1 (Dkk-1), a soluble inhibitor of the Wnt signaling pathway, in healthy individuals and in patients with breast cancer (BC) and bone metastases (BM) using a new ELISA. Association of serum Dkk-1 with markers of bone turnover was also investigated. Serum Dkk-1 measurements were performed using a commercial sandwich ELISA in 150 healthy men, 175 healthy pre- and postmenopausal women (20-65 years), 22 women with BC and BM (mean age 63 years), and 16 women with BC and metastases at sites other than bone (mean age 53 years). Intra- and interassay coefficients of variation were below 7% and 12%, respectively. The detection limit was determined to be 0.018 microg/L. In healthy women and men, Dkk-1 did not change with age. Serum Dkk-1 modestly correlated with serum bone alkaline phosphatase (r = 0.19, P = 0.013) and serum C-terminal cross-linking telopeptide of type I collagen (r = 0.19, P = 0.014) in women but not in men. Dkk-1 levels were higher in women with BC and BM (5.57 +/- 5.50 microg/L) than in healthy age-matched controls (3.47 +/- 1.47 microg/L, P < 0.0001) and women with metastases at sites other than bone (3.57 +/- 1.66 microg/L, P = 0.0003). In conclusion, serum Dkk-1 is stable with age in healthy women and men and increases in patients with BC and BM. Measurements of circulating Dkk-1 with this new ELISA may be useful for the clinical investigation of patients with malignant bone diseases.

Effectiveness and cost of bisphosphonate therapy in tumor bone disease.

BACKGROUND: Tumor-induced osteolysis due to breast carcinoma and myeloma is responsible for a considerable morbidity that severely impairs patients'quality of life. Osteoclast-mediated bone resorption is reported to be increased markedly in patients with tumor bone disease and can be inhibited by bisphosphonate therapy. METHODS: The incidence of skeletal complications and the effectiveness of bisphosphonate therapy in patients with breast carcinoma metastatic to bone or in those with myeloma were derived from large-scale, long-term, placebo-controlled trials with clodronate or pamidronate. To the authors' knowledge, there are few studies published to date evaluating the cost-effectiveness of bisphosphonate therapy, and the majority that do exist often are based on models and are applicable only to a particular health care system. RESULTS: From the placebo groups of the above-mentioned trials, one can estimate that approximately 25-40% of the patients with breast carcinoma metastatic to bone will require radiotherapy for bone pain and approximately 17-50% will sustain incident vertebral fractures yearly. The incidence of complications is reported to be lower in myeloma patients. The prolonged administration of bisphosphonates reportedly can reduce the frequency of skeletal-related events by approximately 25-50%. Maximal efficacy appears to have been achieved with the current therapeutic schemes based on monthly intravenous infusions. Beneficial effects appear to be obtained more readily using the intravenous route rather than the oral route. The costs of bisphosphonate therapy appear to be higher than the cost savings from the prevention of skeletal-related events. The costs per quality of life-adjusted year have been estimated to be > $100,000, but more research is needed. Limited data suggest that zoledronic acid will not reduce treatment costs but the short infusion time will lead to substantial time savings for patients and for outpatient oncology facilities. CONCLUSIONS: As is the case for many agents used in oncology, bisphosphonates remain a relatively expensive therapy. More studies are needed to evaluate their cost-effectiveness ratio correctly. A ceiling effect has been reached with current therapeutic schemes and tailoring therapy to the individual patient needs to be evaluated correctly to increase therapeutic effectiveness and improve quality of life further without increasing treatment costs.