The Effect of 3 or 6 Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the FREEDOM Extension.
; ; et al
in The Journal of clinical endocrinology and metabolism (2013)
Context:The FREEDOM extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years.Objective:Report results from the first 3 years of the extension, representing up to 6 years ... [more ▼]
Context:The FREEDOM extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years.Objective:Report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure.Design, Setting, and Participants: Multicenter, international, open-label study of 4550 women.Intervention:Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (cross-over).Main Outcome Measures:Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety.Results:Reductions in BTMs were maintained (long-term) or achieved rapidly (cross-over) following denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the cross-over group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below rates projected for a "virtual placebo" cohort. In the cross-over group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of ONJ confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture.Conclusion:Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low. [less ▲]Detailed reference viewed: 24 (2 ULg)
Erratum to: Vitamin D Status and Bone Mineral Density Changes During Alendronate Treatment in Postmenopausal Osteoporosis.
; ; et al
in Calcified tissue international (2013)Detailed reference viewed: 12 (1 ULg)
Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporotic women.
Hiligsmann, Mickaël ; ; et al
in Expert review of pharmacoeconomics & outcomes research (2013), 13(1), 19-28
Denosumab is a novel biological agent for the treatment of osteoporosis in postmenopausal women with increased risk of fractures. With limited healthcare resources, economic evaluations are increasingly ... [more ▼]
Denosumab is a novel biological agent for the treatment of osteoporosis in postmenopausal women with increased risk of fractures. With limited healthcare resources, economic evaluations are increasingly being used by decision-makers to optimize healthcare resource allocation. The cost-effectiveness of denosumab has been evaluated in various studies, and a systematic literature study was conducted up to April 2012 to identify all published research articles and research abstracts presented at various congresses. This article provides a systematic review of four articles and eight abstracts reporting on the cost-effectiveness of denosumab in the treatment of osteoporosis. In most economic evaluations, denosumab has been considered as a cost-effective treatment compared with first-line and second-line options (including generic alendronate) in the treatment of women with high risk of fractures. [less ▲]Detailed reference viewed: 16 (3 ULg)
Erratum to : Recommendations for the health economics analysis to be performed with a drug to be registered in prevention or treatment of osteoporosis
; ; et al
in Calcified Tissue International (2013), 93Detailed reference viewed: 22 (1 ULg)
What do we know about the safety of corticosteroids in rheumatoid arthritis?
Ethgen, Olivier ; De Lemos Esteves, Frédéric ; Bruyère, Olivier et al
in Current Medical Research & Opinion (2013), 29(9), 1147-60
Abstract Background: Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience. Scope: We performed a literature search in Ovid ... [more ▼]
Abstract Background: Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience. Scope: We performed a literature search in Ovid MEDLINE from January 2000 to December 2012. Our Population Intervention Comparator Outcomes (PICO) strategy search was: rheumatoid arthritis [Population], corticosteroids or glucocorticoids [Intervention], any comparison [Comparator], adverse effects [Outcome]. Studies were selected if they reported any measure of association between GCs intake and potential adverse effects in RA patients. Findings: We identified 1030 papers and selected for analysis 26 observational studies and six systematic reviews. The major side effects of GCs in RA are bone loss, risk of cardiovascular events and risk of infections as evidenced by large observational studies and not necessarily RCTs. Others associations were reported with herpes zoster, tuberculosis, hyperglycemia, cutaneous abnormalities, gastrointestinal perforation, respiratory infection and self-reported health problems such as cushingoid phenotype, ecchymosis, parchment-like skin, epistaxis, weight gain and sleep disturbance. Other potential adverse effects of GCs were studied but no association was found. These included psychological disorders, dermatophytosis, brain diseases, interstitial lung disease, memory deficit, metabolic syndrome, lymphoma, non-Hodgkin's lymphoma, renal function and cerebrovascular accidents. Most of the evidence emanates from observational researches and the inherent limitations of such data should be kept in mind. Conclusion: Recent observational data and systematic reviews suggest that GCs can lead to relatively alarming and burdensome side effects in RA. This is particularly true for patients who have longer term and higher dose therapies. GCs are largely used in RA and knowing their safety profile is essential to improve patients care. The design of new therapeutic strategies intended to minimize the daily dosing of GCs while conserving their beneficial effect should be encouraged. [less ▲]Detailed reference viewed: 31 (17 ULg)
Tools in the assessment of sarcopenia.
; ; et al
in Calcified Tissue International (2013), 93(3), 201-10
This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the ... [more ▼]
This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate end points for determining outcomes of clinical importance which might be utilized in intervention studies. We review current approaches to the definition of sarcopenia and the methods used for the assessment of various aspects of physical function in older people. The potential end points of muscle mass, muscle strength, muscle power, and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these end points in clinical trials. Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomized clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area. [less ▲]Detailed reference viewed: 18 (4 ULg)
Cost-effectiveness of bazedoxifene compared with raloxifene in the treatment of postmenopausal osteoporotic women.
Hiligsmann, Mickaël ; Ben Sedrine, Wafa ; REGINSTER, Jean-Yves
in Journal of Bone and Mineral Research (2013), 28(4), 807-15
Bazedoxifene is a novel selective estrogen receptor modulator (SERM) for the prevention and treatment of osteoporosis. In addition to the therapeutic value of a new agent, evaluation of the cost ... [more ▼]
Bazedoxifene is a novel selective estrogen receptor modulator (SERM) for the prevention and treatment of osteoporosis. In addition to the therapeutic value of a new agent, evaluation of the cost-effectiveness compared with relevant alternative treatment(s) is an important consideration to facilitate healthcare decision making. This study evaluated the cost-effectiveness of bazedoxifene compared with raloxifene for the treatment of postmenopausal women with osteoporosis. The cost-effectiveness of treatment for 3 years with bazedoxifene was compared with raloxifene using an updated version of a previously validated Markov microsimulation model. Analyses were conducted from a Belgian healthcare payer perspective and, the base-case population was women (aged 70 years) with bone mineral density T-score </= -2.5. The effects of bazedoxifene and raloxifene on fracture risk were derived from the 3-year results of a randomized, double-blind, placebo-controlled and active-controlled study, including postmenopausal women with osteoporosis. The cost-effectiveness analysis based on efficacy data from the overall clinical trial indicated that bazedoxifene and raloxifene were equally cost-effective. When the results were examined based on the subgroup analysis of women at higher risk of fractures, bazedoxifene was dominant (lower cost for higher effectiveness) compared with raloxifene in most of the simulations. Sensitivity analyses confirmed the robustness of the results, which were largely independent of starting age of treatment, fracture risk, cost, and disutility. In addition, when the cost of raloxifene was reduced by one-half or when incorporating the raloxifene effects on reducing breast cancer, bazedoxifene remained cost-effective, at a threshold of euro35,000 per quality-adjusted life-years gained, in 85% and 68% of the simulations, respectively. Under the assumption of improved antifracture efficacy of bazedoxifene over raloxifene in women with high risk of fractures, this study suggests that bazedoxifene can be considered cost-effective, and even dominant, when compared with raloxifene in the treatment of postmenopausal osteoporotic women. [less ▲]Detailed reference viewed: 19 (4 ULg)
Nutrition and bone health : turning beliefs into knowledge for healthy behaviour
; Reginster, Jean-Yves
in Osteoporosis International (2013), 24(1), 388-389Detailed reference viewed: 21 (3 ULg)
Inhibition of sclerostin with romosozumab in postmenopausal women with low BMD : phase 2 trial results
; ; et al
in Osteoporosis International (2013), 24(1), 38-39Detailed reference viewed: 95 (3 ULg)
Patients' preferences for osteoporosis drug therapy : a discrete choice experiment
Hiligsmann, Mickaël ; ; et al
in Osteoporosis International (2013), 24(1), 53Detailed reference viewed: 11 (3 ULg)
Pharmacological management : osteoporosis and osteoarthritis, similarities and differences
in Osteoporosis International (2013), 24(1), 75-76Detailed reference viewed: 5 (2 ULg)
The general approach to the patient with osteoarthritis : is a treatment algorithm feasible ?
in Osteoporosis International (2013), 24(1), 385Detailed reference viewed: 7 (2 ULg)
Strontium ranelate effect on knee osteoarthritis progression : a MRI analysis
; ; et al
in Osteoporosis International (2013), 24(1), 312-313Detailed reference viewed: 33 (2 ULg)
Strontium ranelate prevents radiological progression in patients with primary knee osteoarthritis
; ; et al
in Osteoporosis International (2013), 24(1), 306-307Detailed reference viewed: 19 (2 ULg)
Indirect comparison of bazedoxifene vs. oral bisphosphonates for the prevention of vertebral fractures in postmenopausal osteoporotic women
Reginster, Jean-Yves ; ; et al
in Osteoporosis International (2013), 24(1), 37Detailed reference viewed: 45 (7 ULg)
ACP Journal Club: supplementation with vitamin D did not reduce cartilage volume loss or pain in knee osteoarthritis.
REGINSTER, Jean-Yves ;
in Annals of Internal Medicine (2013), 158(8), 9Detailed reference viewed: 14 (5 ULg)
Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).
; ; et al
in Current Medical Research & Opinion (2013), 29(4), 305-13
Abstract Background: Vitamin D insufficiency has deleterious consequences on health outcomes. In elderly or postmenopausal women, it may exacerbate osteoporosis. Scope: There is currently no clear ... [more ▼]
Abstract Background: Vitamin D insufficiency has deleterious consequences on health outcomes. In elderly or postmenopausal women, it may exacerbate osteoporosis. Scope: There is currently no clear consensus on definitions of vitamin D insufficiency or minimal targets for vitamin D concentrations and proposed targets vary with the population. In view of the potential confusion for practitioners on when to treat and what to achieve, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) convened a meeting to provide recommendations for clinical practice, to ensure the optimal management of elderly and postmenopausal women with regard to vitamin D supplementation. Findings: Vitamin D has both skeletal and extra-skeletal benefits. Patients with serum 25-hydroxyvitamin D (25-(OH)D) levels <50 nmol/L have increased bone turnover, bone loss, and possibly mineralization defects compared with patients with levels >50 nmol/L. Similar relationships have been reported for frailty, nonvertebral and hip fracture, and all-cause mortality, with poorer outcomes at <50 nmol/L. Conclusion: The ESCEO recommends that 50 nmol/L (i.e. 20 ng/mL) should be the minimal serum 25-(OH)D concentration at the population level and in patients with osteoporosis to ensure optimal bone health. Below this threshold, supplementation is recommended at 800 to 1000 IU/day. Vitamin D supplementation is safe up to 10,000 IU/day (upper limit of safety) resulting in an upper limit of adequacy of 125 nmol/L 25-(OH)D. Daily consumption of calcium- and vitamin-D-fortified food products (e.g. yoghurt or milk) can help improve vitamin D intake. Above the threshold of 50 nmol/L, there is no clear evidence for additional benefits of supplementation. On the other hand, in fragile elderly subjects who are at elevated risk for falls and fracture, the ESCEO recommends a minimal serum 25-(OH)D level of 75 nmol/L (i.e. 30 ng/mL), for the greatest impact on fracture. [less ▲]Detailed reference viewed: 18 (11 ULg)
Effects of 3 months of short sessions of controlled whole body vibrations on the risk of falls among nursing home residents
Beaudart, Charlotte ; Maquet, Didier ; et al
in BMC Geriatrics (2013), 13(42),
Background: Fatigue, lack of motivation and low compliance can be observed in nursing home residents during the practice of physical activity. Because exercises should not be too vigorous, whole body ... [more ▼]
Background: Fatigue, lack of motivation and low compliance can be observed in nursing home residents during the practice of physical activity. Because exercises should not be too vigorous, whole body vibration could potentially be an effective alternative. The objective of this randomized controlled trial was to assess the impact of 3-month training by whole body vibration on the risk of falls among nursing home residents. Methods: Patients were randomized into two groups: the whole body vibration group which received 3 training sessions every week composed of 5 series of only 15 seconds of vibrations at 30 Hz frequency and a control group with normal daily life for the whole study period. The impact of this training on the risk of falls was assessed blindly by three tests: the Tinetti Test, the Timed Up and Go test and a quantitative evaluation of a 10-second walk performed with a tri-axial accelerometer. Results: 62 subjects (47 women and 15 men; mean age 83.2 ± 7.99 years) were recruited for the study. No significant change in the studied parameters was observed between the treated (n=31) and the control group (n=31) after 3 months of training by controlled whole-body-vibrations. Actually, the Tinetti test increased of + 0.93 ± 3.14 points in the treated group against + 0.88 ± 2.33 points in the control group (p = 0.89 when adjusted). The Timed Up and Go test showed a median evolution of - 1.14 (− 4.75-3.73) seconds in the treated group against + 0.41 (− 3.57- 2.41) seconds in the control group (p = 0.06). For the quantitative evaluation of the walk, no significant change was observed between the treated and the control group in single task as well as in dual task conditions. Conclusions: The whole body vibration training performed with the exposition settings such as those used in this research was feasible but seems to have no impact on the risk of falls among nursing home residents. Further investigations, in which, for example, the exposure parameters would be changed, seem necessary [less ▲]Detailed reference viewed: 30 (15 ULg)
Relationship between use of antidepressants and risk of fractures: a meta-analysis
Rabenda, Véronique ; Nicolet, Delphine ; Beaudart, Charlotte et al
in Osteoporosis International (2013), 24
Summary It has been shown that antidepressants would have a direct action on bone metabolism and would be associated with increased fracture risk. Results from this large meta-analysis show that both ... [more ▼]
Summary It has been shown that antidepressants would have a direct action on bone metabolism and would be associated with increased fracture risk. Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types. Introduction This study seeks to investigate the relationship between use of antidepressants and the risk of fracture. Methods An exhaustive systematic research of case–control and cohort studies published or performed between 1966 and April 2011 that reported risk estimates of fracture associated with use of antidepressants was performed using MEDLINE, PsycINFO, and the Cochrane Systematic Review Database, manual review of the literature, and congressional abstracts. Inclusion, quality scoring, and data abstraction were performed systematically by three independent reviewers. Results A total of 34 studies (n01,217,464 individuals) were identified. Compared with non-users, the random effects pooled RR of fractures of all types, among antidepressant users, were 1.39 (95%CI 1.32–1.47). Use of antidepressants were associated with a 42 %, 47 %, and 38 % risk increase in non-vertebral, hip, and spine fractures, respectively ([For non-vertebral fractures: RR01.42, 95%CI 1.34–1.51]; [For hip fractures: RR01.47, 95%CI 1.36–1.58]; [For spine fractures: RR01.38, 95%CI 1.19–1.61]). Studies examining SSRI use showed systematically a higher increase in the risk of fractures of all types, non-vertebral, and hip fractures than studies evaluating TCA use. Conclusions Results from this large meta-analysis show that both SSRIs and TCAs are associated with a moderate and clinically significant increase in the risk of fractures of all types. [less ▲]Detailed reference viewed: 46 (23 ULg)