Romosozumab in Postmenopausal Women with Low Bone Mineral Density.
; ; et al
in The New England journal of medicine (2014), 370
Background Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. Methods In a phase 2, multicenter ... [more ▼]
Background Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. Methods In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator - oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 mug daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. Results All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. Conclusions In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532 .). [less ▲]Detailed reference viewed: 38 (6 ULg)
Vitamin D status and bone mineral density changes during alendronate treatment in postmenopausal osteoporosis.
; ; et al
in Calcified tissue international (2014), 94(2), 153-7
Vitamin D supplementation is recommended for women with osteoporosis. In the FOCUS-D trial comparing the combination tablet alendronate plus vitamin D3 5,600 IU (ALN/D) with standard care (SC) prescribed ... [more ▼]
Vitamin D supplementation is recommended for women with osteoporosis. In the FOCUS-D trial comparing the combination tablet alendronate plus vitamin D3 5,600 IU (ALN/D) with standard care (SC) prescribed by patients' personal physicians, ALN/D was more effective in improving serum 25(OH)D and bone turnover markers by 6 months and increasing spine and hip bone mineral density (BMD) after 1 year than SC. This post hoc analysis examined the relationship between BMD gain and 25(OH)D in women in SC receiving alendronate (SC/ALN, n = 134, 52% of the SC group) and in the ALN/D group (n = 257). At baseline, participants were of mean age 73 years and 72% were Caucasian, with a mean 25(OH)D of 14.9 ng/mL. In the SC/ALN group, most received vitamin D, although intake of vitamin D varied extensively (51% received <400 mug/day). In this group, end-of-study 25(OH)D correlated positively with mean percent increases from baseline in lumbar spine and femoral neck BMD [Pearson correlation coefficients (95% CI) = 0.23 (0.02-0.41) and 0.24 (0.03-0.41), respectively]. Baseline 25(OH)D correlated with increases in only lumbar spine BMD [Pearson correlation coefficient (95% CI) = 0.22 (0.01-0.40)]. No correlations between mean BMD change and 25(OH)D were seen with ALN/D. In conclusion, in postmenopausal women with osteoporosis and low 25(OH)D receiving alendronate and a wide range of vitamin D doses, the increase in lumbar spine and femoral neck BMD was positively correlated with serum 25(OH)D achieved by the end of the study and, to some extent, with 25(OH)D concentrations at baseline. The degree of success of alendronate therapy for osteoporosis may depend on the vitamin D status of patients. [less ▲]Detailed reference viewed: 16 (2 ULg)
Quality of life in sarcopenia and frailty
; Reginster, Jean-Yves ; et al
in Calcified Tissue International (2013), 93
The reduced muscle mass and impaired muscle performance that define sarcopenia in older individuals are associated with increased risk of physical limitation and a variety of chronic diseases. They may ... [more ▼]
The reduced muscle mass and impaired muscle performance that define sarcopenia in older individuals are associated with increased risk of physical limitation and a variety of chronic diseases. They may also contribute to clinical frailty. A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities. This review and report of an expert meeting presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarizes QoL concepts and specificities in older populations and examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability, argues that a disease-specific QoL instrumentfor sarcopenia/frailty would be an asset for future research, and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade-off study could be appropriate. [less ▲]Detailed reference viewed: 36 (15 ULg)
Health Technology Assessment in Osteoporosis.
Hiligsmann, Mickaël ; ; et al
in Calcified Tissue International (2013)
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 ... [more ▼]
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 <euro>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. [less ▲]Detailed reference viewed: 23 (10 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)
Nécessité de nouveaux critères de remboursement pour traiter l'ostéoporose en Belgique
Bruyère, Olivier ; ; et al
in Ortho-Rhumato (2012), 10(5), 3Detailed reference viewed: 28 (4 ULg)
Weekly alendronate plus vitamin D3 5,600 IU vs. standard care: effect on serum 25(OH) vitamin D, bone turnover markers, and BMD in osteoporotic postmenopausal women with vitamin D inadequacy - 1 year results of a randomized trial
Reginster, Jean-Yves ; ; et al
in Osteoporosis International (2011, March), 22(Suppl.1), 291-292Detailed reference viewed: 101 (4 ULg)
Antifracture efficacy and safety of once-yearly Zoledronic acid 5mg in men with osteoporosis: a prospective, randomized, controlled trial
; ; et al
in Osteoporosis International (2011, March), 22(Suppl.1), 112Detailed reference viewed: 58 (1 ULg)
Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis.
; Reginster, Jean-Yves ; et al
in Calcified Tissue International (2011), 89(2), 91-104
The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review ... [more ▼]
The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture. [less ▲]Detailed reference viewed: 19 (6 ULg)
Randomized trial of alendronate plus vitamin D3 versus standard care in osteoporotic postmenopausal women with vitamin D insufficiency.
; ; et al
in Calcified Tissue International (2011), 88(6), 485-94
Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D(3) 5,600 IU in a single tablet (ALN/D5600, n = 257 ... [more ▼]
Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D(3) 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients' personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score </=2.5 or </=1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8-20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took >/=800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (-57% vs. -46%, P < 0.001) and bone-specific alkaline phosphatase (-47% vs. -40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D-insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women. [less ▲]Detailed reference viewed: 29 (3 ULg)
Five years treatment with strontium ranelate reduces vertebral and nonvertebral fractures and increases the number and quality of remaining life-years in women over 80 years of age.
; ; et al
in BONE (2010), 46(4), 1038-42
INTRODUCTION: Longevity has resulted in a greater proportion of the population entering a time of life when increasing bone fragility and falls predispose to fractures, particularly nonvertebral fractures ... [more ▼]
INTRODUCTION: Longevity has resulted in a greater proportion of the population entering a time of life when increasing bone fragility and falls predispose to fractures, particularly nonvertebral fractures. Women over 80 years of age constitute 10% of the population but contribute 30% of all fractures and 60% of all nonvertebral fractures. Despite this, few studies have examined antifracture efficacy of treatments in this high-risk group and none has provided evidence for benefits beyond 3 years. MATERIALS AND METHODS: To determine whether strontium ranelate reduces the risk of vertebral and nonvertebral fractures during 5 years, we analyzed a subgroup of 1489 female patients over 80 years of age (mean 83.5+/-3.0 years) with osteoporosis from the SOTI (spinal osteoporosis therapeutic intervention) and TROPOS (treatment of peripheral osteoporosis) studies randomized to strontium ranelate 2 g/d or placebo. All received a supplement of calcium plus vitamin D. RESULTS: By intention to treat, vertebral fracture risk was reduced by 31% (relative risk, RR=0.69; 95% confidence interval, CI 0.52-0.92), nonvertebral fracture risk by 27% (RR=0.73; 95% CI 0.57-0.95), major nonvertebral fracture risk by 33% (RR=0.67; 95% CI 0.50-0.89) and hip fracture risk by 24% (RR=0.76; 95% CI 0.50-1.15, not significant). Treatment was cost-saving as it decreased cost and increased QALYs and life-years. DISCUSSION: Strontium ranelate safely produced a significant reduction in vertebral and nonvertebral fracture risk during 5 years in postmenopausal women over 80 years of age and was cost saving. [less ▲]Detailed reference viewed: 11 (1 ULg)
The effectiveness of inpatient geriatric evaluation and management units: a systematic review and meta-analysis.
; ; et al
in Journal of the American Geriatrics Society (2010), 58(1), 83-92
OBJECTIVES: To examine how geriatric evaluation and management units (GEMUs) are organized and to examine the effectiveness of admission on a GEMU. DESIGN: Systematic review and meta-analysis based on ... [more ▼]
OBJECTIVES: To examine how geriatric evaluation and management units (GEMUs) are organized and to examine the effectiveness of admission on a GEMU. DESIGN: Systematic review and meta-analysis based on literature search of multiple databases and the references lists of all identified articles and by contacting authors. SETTING: GEMUs. PARTICIPANTS: Elderly people admitted to a GEMU. MEASUREMENTS: Quality of the studies was assessed on 10 criteria. The outcome parameters were mortality, institutionalization, functional decline, readmission, and length of stay at different follow-up points. A random-effects meta-analysis was performed using Hedges' gu and variance of relative risk (RR). RESULTS: GEMUs are organized in a heterogeneous way and the included studies gave no thorough description of comprehensive geriatric assessment (CGA). Involvement of a multidisciplinary team was a key element in all GEMUs. The individual trials showed that admission to a GEMU has one or more favorable effects on the outcomes of interest, with two significant effects in the meta-analysis: less functional decline at discharge from the GEMU (RR=0.87, 95% confidence interval (CI)=0.77-0.99; P=.04) and a lower rate of institutionalization 1 year after discharge (RR=0.78, CI=0.66-0.92; P=.003). For the other outcomes in the meta-analysis, a GEMU did not induce significantly different outcomes than usual care. CONCLUSION: This meta-analysis shows a significant effect in favor of the GEMU group on functional decline at discharge and on institutionalization after 1 year. There is heterogeneity between the studies, poor quality of some randomized controlled trials, and shortage of information about CGA. Multidisciplinary CGA offered in a GEMU may add value to the care for frail older persons admitted to the hospital, but the limitations confirm the need for well-designed studies using explicit CGA and more-structured and -coherent assessment instruments such as the Minimum Data Set Resident Assessment Instrument. [less ▲]Detailed reference viewed: 46 (5 ULg)
Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club.
; ; et al
in International Journal of Clinical Practice (2009), 63(1), 19-26
OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate ... [more ▼]
OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency. METHODOLOGY: Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women. RESULTS: Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance. DISCUSSION: Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable. Conclusion: Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication. [less ▲]Detailed reference viewed: 37 (8 ULg)
Strontium ranelate decreases the risk of hip fracture over 3 and 5 years in post menopausal women at high risk
Reginster, Jean-Yves ; ; et al
in Annals of the Rheumatic Diseases (2008, June), 67(Suppl.II), 540Detailed reference viewed: 10 (2 ULg)
Utility audit of Belgian DXA centers
; ; et al
in Osteoporosis International (2008, April), 19(Suppl.1), 205Detailed reference viewed: 5 (1 ULg)
Strontium ranelate demonstrates efficacy against hip fracture over 3 and 5 years in postmenopausal women at high risk of hip fracture
Reginster, Jean-Yves ; ; et al
in Osteoporosis International (2008, April), 19(Suppl.1), 26-27Detailed reference viewed: 11 (1 ULg)
Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: Results of a five-year, randomized, placebo-controlled trial.
Reginster, Jean-Yves ; ; et al
in Arthritis and Rheumatism (2008), 58(6), 1687-95
OBJECTIVE: This study was undertaken to assess the effect of strontium ranelate on nonvertebral and vertebral fractures in postmenopausal women with osteoporosis in a 5-year, double-blind, placebo ... [more ▼]
OBJECTIVE: This study was undertaken to assess the effect of strontium ranelate on nonvertebral and vertebral fractures in postmenopausal women with osteoporosis in a 5-year, double-blind, placebo-controlled trial. METHODS: A total of 5,091 postmenopausal women with osteoporosis were randomized to receive either strontium ranelate at 2 gm/day or placebo for 5 years. The main efficacy criterion was the incidence of nonvertebral fractures. In addition, incidence of hip fractures was assessed, by post hoc analysis, in the subset of 1,128 patients who were at high risk of fractures (age 74 years or older with lumbar spine and femoral neck bone mineral density T scores -2.4 or less). The incidence of new vertebral fractures was assessed, using the semiquantitative method described by Genant, in the 3,646 patients in whom spinal radiography (a nonmandatory procedure) was performed during the course of the study. Fracture data were analyzed using the Kaplan-Meier survival method. RESULTS: Of the 5,091 patients, 2,714 (53%) completed the study up to 5 years. The risk of nonvertebral fracture was reduced by 15% in the strontium ranelate group compared with the placebo group (relative risk 0.85 [95% confidence interval 0.73-0.99]). The risk of hip fracture was decreased by 43% (relative risk 0.57 [95% confidence interval 0.33-0.97]), and the risk of vertebral fracture was decreased by 24% (relative risk 0.76 [95% CI 0.65-0.88]) in the strontium ranelate group. After 5 years, the safety profile of strontium ranelate remained unchanged compared with the 3-year findings. CONCLUSION: Our findings indicate that treatment of postmenopausal osteoporosis with strontium ranelate results in a sustained reduction in the incidence of osteoporotic nonvertebral fractures, including hip fractures, and vertebral fractures over 5 years. [less ▲]Detailed reference viewed: 17 (2 ULg)
Strontium ranelate reduces the risk of fracture in elderly women with osteoporosis in the first year of treatment
; ; et al
in Osteoporosis International (2006, June), 17(Suppl.2), 85-86Detailed reference viewed: 5 (2 ULg)