Quality of life after hip, vertebral, and distal forearm fragility fractures measured using the EQ-5D-3L, EQ-VAS, and time-trade-off: results from the ICUROS.

INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study is a multinational observational study set up to describe the costs and quality of life (QoL) consequences of fragility fracture. This paper aims to estimate and compare QoL after hip, vertebral, and distal forearm fracture using time-trade-off (TTO), the EuroQol (EQ) Visual Analogue Scale (EQ-VAS), and the EQ-5D-3L valued using the hypothetical UK value set. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months after fracture. Health state utility values (HSUVs) were derived for each fracture type and time-point using the three approaches (TTO, EQ-VAS, EQ-5D-3L). HSUV were used to estimate accumulated QoL loss and QoL multipliers. RESULTS: In total, 1410 patients (505 with hip, 316 with vertebral, and 589 with distal forearm fracture) were eligible for analysis. Across all time-points for the three fracture types, TTO provided the highest HSUVs, whereas EQ-5D-3L consistently provided the lowest HSUVs directly after fracture. Except for 13-18 months after distal forearm fracture, EQ-5D-3L generated lower QoL multipliers than the other two methods, whereas no equally clear pattern was observed between EQ-VAS and TTO. On average, the most marked differences between the three approaches were observed immediately after the fracture. CONCLUSIONS: The approach to derive QoL markedly influences the estimated QoL impact of fracture. Therefore the choice of approach may be important for the outcome and interpretation of cost-effectiveness analysis of fracture prevention.

Osteoporosis in Spain: map of resources for diagnosing.

The World Health Organization has warned that osteoporosis (OP) is one of the leading health problems in the Western world because of its high prevalence and social and health implications. Densitometry using dual-energy X-ray absorptiometry (DXA) is the procedure of choice to diagnose OP before fragility fractures occur. The purpose of this study is to quantify and establish the distribution of resources for diagnosis and management of OP in Spain. A secondary objective is to ascertain the available means and the unmet needs of physicians involved in equipment use. The existence and location of central DXA machines both in and out of hospitals was investigated. Their use and performance, as well as current availability and unmet needs by physicians involved in their use were analyzed. Peripheral DXA machines were not included in the census because they can be multicenter and itinerants. Information was obtained from 232 central DXA machines throughout the Spanish territory, of which 43 were for public use, 42 in officially approved hospitals, and 147 in private institutions. The national population coverage was 5.4/million inhabitants. Most of the publicly owned DXAs are in big hospitals (>500 beds) and mainly attend requests from the hospitals themselves. Use of such equipment is mainly clinical in 87%, 88%, and 96% of public, officially approved, and private institutions, respectively. The daily number of densitometries is higher in the public health system compared with private institutions, because equipment is used on average 7h daily, 5d/wk. If only public DXAs are considered, there is an inadequate coverage with territorial differences. The needs expressed by the physicians involved in OP management are not adequately met. Resources should be increased or their efficiency should be modified.

Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate.

UNLABELLED: A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy. INTRODUCTION: Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease. MATERIALS AND METHODS: This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n = 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion. RESULTS: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers. CONCLUSIONS: ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.

Clinical evaluation of novel bisphosphonate dosing regimens in osteoporosis: the role of comparative studies and implications for future studies.

BACKGROUND: Daily nitrogen-containing bisphosphonates have shown antifracture efficacy in many studies of postmenopausal osteoporosis. However, current dosing schedules are often inconvenient or impractical for patients. Efforts to reduce dosing frequency to improve adherence (ie, compliance and persistence), and therefore treatment outcomes, are ongoing. Although a number of trial designs can be used to consider the efficacy of therapy, comparing the efficacy of different regimens should only be undertaken in purposefully designed head-to-head studies. OBJECTIVE: This article summarizes the design and conduct of clinical studies that have investigated alternative bisphosphonate regimens and those that have directly compared different approved bisphosphonates. It also explores the implications for future studies of postmenopausal osteoporosis treatment. METHODS: Using the terms bisphosphonate, daily, weekly, and monthly, a search (completed in 2006) of the PubMed database was conducted to identify primary English-language publications of pertinent studies comparing either novel with established regimens of the same bisphosphonates or different established bisphosphonates. RESULTS: The first option is the equivalence or noninferiority bridging study for comparison of new treatment regimens versus the established regimen of the same bisphosphonate, known as the active comparator. Four such studies have led to the registration of novel bisphosphonate dosing regimens designed to provide easier dosing alternatives for patients. The second option is the active comparator study, which compares one bisphosphonate with the most prescribed weekly bisphosphonate. Weekly dosed oral alendronate has previously been shown to be superior (for bone mineral density gains) to daily and weekly dosed oral risedronate. An ongoing noninferiority study, Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention, is comparing weekly alendronate with ibandronate, a monthly oral bisphosphonate. CONCLUSIONS: The exploration of new dosing schedules and formulations aims to identify the optimal bisphosphonate regimen for postmenopausal osteoporosis. To achieve this, careful consideration must be given to the choice of a scientifically valid study design that effectively, and ethically, meets the study objectives. Given the concerns regarding placebo-controlled antifracture studies, 2 alternative study designs should be considered, both using validated surrogate end points (bone mineral density and biochemical markers of bone turnover) as the principal mode of assessment.