Strontium ranelate in the treatment of knee osteoarthritis: new insights and emerging clinical evidence.
REGINSTER, Jean-Yves ; Beaudart, Charlotte ; et al
in Therapeutic advances in musculoskeletal disease (2013), 5(5), 268-276
Osteoarthritis is a primary cause of disability and functional incapacity. Pharmacological treatment is currently limited to symptomatic management, and in advanced stages, surgery remains the only ... [more ▼]
Osteoarthritis is a primary cause of disability and functional incapacity. Pharmacological treatment is currently limited to symptomatic management, and in advanced stages, surgery remains the only solution. The therapeutic armamentarium for osteoarthritis remains poor in treatments with an effect on joint structure, that is, disease-modifying osteoarthritis drugs (DMOADs). Glucosamine sulfate and chondroitin sulfate are the only medications for which some conclusive evidence for a disease-modifying effect is available. Strontium ranelate is currently indicated for the prevention of fracture in severe osteoporosis. Its efficacy and safety as a DMOAD in knee osteoarthritis has recently been explored in the SEKOIA trial, a 3-year randomized, double-blind, placebo-controlled trial. Outpatients with knee osteoarthritis, Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) of 2.5-5 mm received strontium ranelate 1 g/day (n = 558) or 2 g/day (n = 566), or placebo (n = 559). This sizable population was aged 62.9 years and had a JSW of 3.50 +/- 0.84 mm. Treatment with strontium ranelate led to significantly less progression of knee osteoarthritis: estimates for annual difference in joint space narrowing versus placebo were 0.14 mm [95% confidence interval (CI) 0.05-0.23 mm; p < 0.001] for 1 g/day and 0.10 mm (95% CI 0.02-0.19 mm; p = 0.018) for 2 g/day, with no difference between strontium ranelate groups. Radiological progression was less frequent with strontium ranelate (22% with 1 g/day and 26% with 2 g/day versus 33% with placebo, both p < 0.05), as was radioclinical progression (8% and 7% versus 12%, both p < 0.05). Symptoms also improved with strontium ranelate 2 g/day only in terms of total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score (p = 0.045), and its components for pain (p = 0.028) and physical function (p = 0.099). Responder analyses using a range of criteria for symptoms indicated that the effect of strontium ranelate 2 g/day on pain and physical function was clinically meaningful. Strontium ranelate was well tolerated. The observation of both structure and symptom modification with strontium ranelate 2 g/day makes SEKOIA a milestone in osteoarthritis research and treatment. [less ▲]Detailed reference viewed: 17 (9 ULg)
Impact of chondroitin sulphate on health utility in patients with knee osteoarthritis: towards economic analysis.
Bruyère, Olivier ; ; et al
in Journal of Medical Economics (2009), 12(4), 356-360
Abstract Objectives: The first objective was to assess the effect of the chondroitin 4 and 6 sulphate (CS) on health-related quality of life using utility values in patients with knee osteoarthritis (OA ... [more ▼]
Abstract Objectives: The first objective was to assess the effect of the chondroitin 4 and 6 sulphate (CS) on health-related quality of life using utility values in patients with knee osteoarthritis (OA) during a 24-month treatment course. The second objective was, using these data, to conduct economic analyses. Methods: Data from the STOPP study was used. This study was a randomised, double-blind, placebo (PL) -controlled trial of 2-year duration. In the STOPP study, authors assessed quality of life using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). WOMAC scores were translated into Health Utility Index (HUI) scores using a specific formula. Incremental cost effectiveness ratio (ICER) was calculated taking into account the cost of CS and its effect on HUI scores, compared to PL. Results: At baseline, the mean (SD) HUI scores were 0.59 (0.17), and 0.59 (0.18) for the PL and CS groups, respectively (p=0.31 between the two groups). The mean (SD) HUI scores changes from baseline to 6 months were 0.02 (0.02), and 0.05 (0.01) for the PL and CS groups, respectively (p=0.03). After 24 months of follow-up, HUI score increases by 0.04 (0.02) in the PL group and by 0.05 (0.02) in the CS group (p=0.37). Using the price bracket of CS in Europe, ICER assessment always resulted in a cost below euro30,000 per QALY gained, after 6, 12 and 24 months of treatment. Conclusion: CS treatment increases health utilities in patients with knee OA compared to PL over the first 6 months of treatment. Economic evaluation based on these data suggests that CS treatment could be considered as cost-effective in patients with knee OA up to a period of 24 months. A limitation in this study is the absence of direct utility assessment as well as the absence of effective treatment as comparator. [less ▲]Detailed reference viewed: 58 (17 ULg)
Strontium ranelate: new data on fracture prevention and mechanisms of action.
Reginster, Jean-Yves ; Deroisy, Rita ; et al
in Current Osteoporosis Reports (2009), 7(3), 96-102
Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile that optimizes therapeutic adherence ... [more ▼]
Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile that optimizes therapeutic adherence. Strontium ranelate is the first compound to simultaneously decrease bone resorption and stimulate bone formation. Its anti-fracture efficacy at various skeletal sites has been established for as long as 5 years through studies of the highest methodological standards. Increases in bone mineral density observed after 1 year of treatment are predictive of the long-term fracture efficacy, suggesting for the first time in osteoporosis that bone densitometry can be used as a monitoring tool. Due to a positive risk/benefit ratio, strontium ranelate is now considered as a first-line treatment in the management of osteoporosis. [less ▲]Detailed reference viewed: 35 (1 ULg)
Role of Biochemical Markers of Bone Turnover as Prognostic Indicator of Successful Osteoporosis Therapy
Reginster, Jean-Yves ; Collette, Julien ; et al
in BONE (2008), 42
Most of the currently available anti-osteoporosis medications promptly and significantly influence the rate of bone turnover. Biochemical markers of bone turnover now provide a high sensitivity to change ... [more ▼]
Most of the currently available anti-osteoporosis medications promptly and significantly influence the rate of bone turnover. Biochemical markers of bone turnover now provide a high sensitivity to change, allowing the detection of these bone turnover changes within a couple of weeks. Since the anti-fracture efficacy of inhibitors of bone resorption or stimulators of bone formation appears to be largely independent of baseline bone turnover, biochemical markers do not appear to play a significant role in the selection of one particular drug, for an individual patient. However, there are consistent data showing that short-term changes in biochemical markers of bone turnover may be significant predictors of future changes in bone mineral density or fracture reduction, hence suggesting that bone turnover markers play a significant role in the monitoring of anti-osteoporosis therapy. [less ▲]Detailed reference viewed: 63 (11 ULg)
Strontium ranelate: The first agent of a new therapeutic class in osteoporosis.
; Hiligsmann, Mickaël ; Scholtissen, Sophie et al
in Advances in Therapy (2008), 25(12), 1235-56
Strontium ranelate is a new agent developed for the management of post-menopausal osteoporosis. It has a unique mode of action, based on an uncoupling between bone formation (increased) and bone ... [more ▼]
Strontium ranelate is a new agent developed for the management of post-menopausal osteoporosis. It has a unique mode of action, based on an uncoupling between bone formation (increased) and bone resorption (decreased). To review its effectiveness we searched the MEDLINE database from 1985 to 2008, as well as databases such as the Cochrane controlled register, for citations or relevant articles. After this extensive search of the literature, a critical appraisal of the data was obtained through a consensus meeting (AN, MH, SS, OB, and J-YR). We found that strontium ranelate reduces vertebral, nonvertebral, major nonvertebral, and hip fractures over 1, 3, 4, and 5 years. Its spectrum of activity covers women with osteopenia, osteoporosis, and severe osteoporosis. Elderly subjects also show a reduction in vertebral and nonvertebral fractures. Bone mineral density may be used as a monitoring tool for strontium ranelate, since early changes are predictive of long-term fracture reduction. Biochemical markers of bone turnover reflect the uncoupling between resorption and formation. The safety profile of strontium ranelate compares favorably with the other currently marketed antiosteoporosis medications. Preliminary results suggest that strontium ranelate is able to reduce the progression of spine osteoarthritis. In conclusion, strontium ranelate has the potential to be a candidate for first-line treatment of osteopenia and osteoporosis. However, further research is needed before suggesting its widespread use in osteoarthritis. [less ▲]Detailed reference viewed: 34 (6 ULg)
Ibandronate in profile: drug characteristics and clinical efficacy.
Reginster, Jean-Yves ; ; Bruyère, Olivier
in Expert Opinion on Drug Metabolism & Toxicology (2008), 4(7), 941-51
BACKGROUND: Postmenopausal osteoporosis is a serious, chronic condition, for which nitrogen-containing bisphosphonates are now one of the treatments of choice. OBJECTIVE: To review the profile of ... [more ▼]
BACKGROUND: Postmenopausal osteoporosis is a serious, chronic condition, for which nitrogen-containing bisphosphonates are now one of the treatments of choice. OBJECTIVE: To review the profile of ibandronate, a monthly oral (150 mg) or quarterly intravenous injection (3 mg) of bisphosphonate. METHODS: The literature search was limited to publications of ibandronate data. RESULTS/CONCLUSION: Ibandronate is rapidly absorbed and distributed in the bone; it is not metabolised and is excreted in urine. Clinical trial data have demonstrated the efficacy of ibandronate in reducing fracture risk, increasing bone mineral density and reducing bone turnover. These data are supported by recent meta-analyses and a large database study that have demonstrated antifracture efficacy with the ibandronate regimens used in clinical practice. Overall, ibandronate has generally been well tolerated. Therefore, ibandronate is a useful treatment for postmenopausal osteoporosis. [less ▲]Detailed reference viewed: 36 (4 ULg)
Bone-forming agents in the management of osteoporosis.
; Reginster, Jean-Yves
in Best Practice & Research. Clinical Endocrinology & Metabolism (2008), 22(5), 869-83
Women often consult for the first time after osteoporosis has already become established. Medications have therefore been developed which can stimulate bone formation, with the ultimate goal of restoring ... [more ▼]
Women often consult for the first time after osteoporosis has already become established. Medications have therefore been developed which can stimulate bone formation, with the ultimate goal of restoring bone quantity and quality and reducing spinal and peripheral fractures to a greater extent than can be obtained with inhibitors of bone resorption. Peptides of the parathyroid hormone family, when given intermittently, increase the number and activity of osteoblasts, leading to an increase in bone mass and in an improvement in skeletal architecture. Teriparatide (1-34 parathyroid hormone, PTH) reduces vertebral and non-vertebral fractures at a dose of 20 microg/day given in subcutaneous daily injections. 1-84 PTH reduces vertebral fractures, but results on non-vertebral fractures are lacking. Strontium ranelate, suggested to uncouple bone formation from bone resorption, reduces vertebral, non-vertebral and hip fractures in osteoporotic patients aged >74 years. Reduction of a vertebral fracture has also been shown in osteopenic patients. Long-term (5-year) data are available on vertebral, non-vertebral, major non-vertebral and hip fractures in osteoporotic patients. Combination/sequential treatments using inhibitors of bone resorption and bone-forming agents have been assessed in a variety of regimens. Benefits from the use of bone-forming agents appear to be largely independent of previous treatment with inhibitors of bone resorption. After treatment with an anabolic agent, the use of anti-resorptive medications maintains the benefit of the former treatment. Concomitant use of an inhibitor of bone resorption and a stimulator of bone formation has not, so far, showed any additional benefit compared with each medication given alone. [less ▲]Detailed reference viewed: 27 (3 ULg)
Current role of glucosamine in the treatment of osteoarthritis
Reginster, Jean-Yves ; Bruyère, Olivier ;
in Rheumatology (2007), 46(5), 731-735
Objectives. To evaluate the interest of using the various preparations of glucosamine for symptomatic and structural management of osteoarthritis (OA). Methods. A critical analysis of the literature based ... [more ▼]
Objectives. To evaluate the interest of using the various preparations of glucosamine for symptomatic and structural management of osteoarthritis (OA). Methods. A critical analysis of the literature based on an exhaustive search (Medline, PubMed and manual search within the bibliography of retrieved manuscripts) from 1980 to 2005. Results. Despite multiple controlled clinical trials of the use of glucosamine in OA (mainly of the knee), controversy on efficacy related to symptomatic improvement continues. Differences in results originate from the differences in products, study design and study populations. Symptomatic efficacy described in multiple studies performed with glucosamine sulphate (GS) support continued consideration in the OA therapeutic armamentarium. The most compelling evidence of a potential for inhibiting the progression of OA is also obtain with GS. Conclusions. GS has shown positive effects on symptomatic and structural outcomes of knee OA. These results should not be extrapolated to other glucosamine salts [hydrochloride or preparations (over-the-counter or food supplements)] in which no warranty exists about content, pharmacokinetics and pharmacodynamics of the tablets. [less ▲]Detailed reference viewed: 12 (5 ULg)
Strontium ranelate in the prevention of osteoporotic fractures
Reginster, Jean-Yves ; Malaise, Olivier ; et al
in International Journal of Clinical Practice (2007), 61(2), 324-328
Osteoporosis results from a decrease in bone strength yielding increased susceptibility to fractures. Hip and spine fractures are a major cause of morbidity and mortality in the elderly population. With ... [more ▼]
Osteoporosis results from a decrease in bone strength yielding increased susceptibility to fractures. Hip and spine fractures are a major cause of morbidity and mortality in the elderly population. With an increasingly ageing world population, early prevention of bone loss is essential for adequate control of this condition. Strontium ranelate (PROTELOS (R)), an oral drug for postmenopausal osteoporosis, has been reported to decrease bone resorption and to stimulate bone formation. The efficacy in reducing vertebral fractures, non-vertebral including hip fractures, and the safety of strontium ranelate has been initially demonstrated over 3 years in the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (TReatment Of Peripheral OSteoporosis) studies and confirmed recently over up to 5 years. A preplanned analysis of a sub-group of patients aged 80 years and over showed that, currently, strontium ranelate is the only antiosteoporotic agent to reduce vertebral and non-vertebral fractures in this age group. [less ▲]Detailed reference viewed: 24 (4 ULg)