Antifracture Efficacy Of Strontium Ranelate Research Articles

The position of strontium ranelate in today's management of osteoporosis.

Osteoporosis accounts for about 3 % of total European health-care spending. The low proportion of costs for the pharmacological prevention of osteoporotic fracture means that it is highly cost saving, especially in patient with severe osteoporosis or patients who cannot take certain osteoporosis medications due to issues of contraindications or tolerability. Following recent regulatory changes, strontium ranelate is now indicated in patients with severe osteoporosis for whom treatment with other osteoporosis treatments is not possible, and without contraindications including uncontrolled hypertension, established, current or past history of ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. We review here today's evidence for the safety and efficacy of strontium ranelate. The efficacy of strontium ranelate in patients complying with the new prescribing information (i.e. severe osteoporosis without contraindications) has been explored in a multivariate analysis of clinical trial data, which concluded that the antifracture efficacy of strontium ranelate is maintained in patients with severe osteoporosis without contraindications and also demonstrated how the new target population mitigates risk. Strontium ranelate is therefore an important alternative in today's management of osteoporosis, with a positive benefit-risk balance, provided that the revised indication and contraindications are followed and cardiovascular risk is monitored. The bone community should be reassured that there remain viable alternatives in patients in whom treatment with other agents is not possible and protection against the debilitating effects of fracture is still feasible in patients with severe osteoporosis.

A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®

The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability. Two previous studies have suggested that the efficacy of intervention may be greater in the segment of the population at highest fracture risk as assessed by the FRAX(®) algorithms. The aim of the present study was to determine whether the anti-fracture efficacy of strontium ranelate was dependent of the level of fracture risk. The primary data of the two phase III studies (SOTI and TROPOS) of the effects of strontium ranelate in postmenopausal osteoporosis were combined. Country-specific probabilities were computed using the FRAX(®) tool (version 2.0). The primary outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.5% to 90.8%. FRAX(®)-based hip fracture probabilities ranged from 0.1% to 90.3%. The incidence of clinical osteoporotic fractures (vertebral fractures excluded) and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with strontium ranelate was associated with a 31% (95% CI = 20-39%) decrease in osteoporotic clinical fractures and a 40% decrease in vertebral fractures assessed by semiquantitative morphometry (95% CI = 31-48%) Hazard ratios for the effect of strontium ranelate on the fracture outcomes did not change significantly with increasing fracture probability. Strontium ranelate significantly decreased the risk of osteoporotic clinical fractures, non vertebral fractures and morphometric vertebral fractures in women. Overall, the efficacy of strontium ranelate was not dependent of the level of fracture risk assessed by FRAX.

Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis

The structural basis of the antifracture efficacy of strontium ranelate and alendronate is incompletely understood. We compared the effects of strontium ranelate and alendronate on distal tibia microstructure over 2 years using HR-pQCT. In this pre-planned, interim, intention-to-treat analysis at 12 months, 88 osteoporotic postmenopausal women (mean age 63.7 ± 7.4) were randomized to strontium ranelate 2 g/day or alendronate 70 mg/week in a double-placebo design. Primary endpoints were changes in microstructure. Secondary endpoints included lumbar and hip areal bone mineral density (aBMD), and bone turnover markers. This trial is registered with http://www.controlled-trials.com, number ISRCTN82719233. Baseline characteristics of the two groups were similar. Treatment with strontium ranelate was associated with increases in mean cortical thickness (CTh, 5.3%), cortical area (4.9%) and trabecular density (2.1%) (all P < 0.001, except cortical area P = 0.013). No significant changes were observed with alendronate. Between-group differences in favor of strontium ranelate were observed for CTh, cortical area, BV/TV and trabecular density (P = 0.045, 0.041, 0.048 and 0.035, respectively). aBMD increased to a similar extent with strontium ranelate and alendronate at the spine (5.7% versus 5.1%, respectively) and total hip (3.3% versus 2.2%, respectively). No significant changes were observed in remodeling markers with strontium ranelate, while suppression was observed with alendronate. Within the methodological constraints of HR-pQCT through its possible sensitivity to X-ray attenuation of different minerals, strontium ranelate had greater effects than alendronate on distal tibia cortical thickness and trabecular volumetric density.

Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture

Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture. The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures. Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry. Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9weeks of the study (-60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, -39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (-39%, -21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women. This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture.

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover

SummaryOsteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels.IntroductionBone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels.MethodsPost-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo.ResultsIn the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290).ConclusionThe vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states.

Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis

Objectives:Early osteoporotic fractures have a great impact on disease progression, the first fracture being a major risk factor for further fractures. Strontium ranelate efficacy against vertebral fractures is presently assessed...

Strontium ranelate normalizes bone mineral density in osteopenic patients

To assess the capacity of strontium ranelate to restore normal bone mineral density (WHO definition: T-score >or=-1) in post-menopausal osteopenic women (T-score between -1 and -2.5) at baseline. Post-hoc analysis from SOTI and TROPOS studies of 1428 patients randomly assigned to receive either 2 g of strontium ranelate a day or placebo for three years. Bone mineral density was measured at baseline and each year for three years. Results were analyzed on an intention-to-treat basis. At lumbar spine, after one, two and three years of treatment with strontium ranelate, 26.4, 42.1 and 58.2% respectively of osteopenic patients normalized their bone mineral density, compared with 6.6, 8.9 and 11.9% in the placebo group (all p<0.001). At total hip, the percentage of patients normalizing their bone mineral density was 5.4, 10.0 and 19.6% in the strontium ranelate group and 1.8, 1.4 and 1.6% in the placebo one (all p<0.001). Strontium ranelate is able to normalize bone mineral density in a significant proportion of osteopenic patients after one, two and three years of treatment. The clinical relevance of these results should be confirmed by direct demonstration of the anti-fracture efficacy of strontium ranelate in osteopenic patients.

Antifracture efficacy of strontium ranelate in postmenopausal osteoporosis

Strontium ranelate is a bone-seeking element that has been assessed in postmenopausal osteoporosis in two large double-blind, placebo-controlled studies. This treatment is able to decrease the risk of vertebral fractures, by 38% over 3 years, and by 52% within the first year of treatment. Moreover, in postmenopausal patients with osteoporosis, the risk of having a first vertebral fracture is decreased by 48% after 3 years. The risk of nonvertebral fractures is decreased by 16%, and, in patients at high risk for such a fracture, the risk of hip fracture is decreased by 36% over 3 years. Recent 5-year data from these double-blind, placebo-controlled studies show that the antifracture efficacy is maintained over time. Current recommendations for therapeutic decision-making in osteoporosis are based on risk factor assessment; treatment efficacy with strontium ranelate has been documented across a wide range of patient profiles: age, bone mineral density, body mass index, as well as family history of osteoporosis and addiction to smoking are not determinants of antifracture efficacy. Strontium ranelate is an attractive treatment option across the postmenopausal osteoporosis continuum.

Strontium ranelate: An increased bone quality leading to vertebral antifracture efficacy at all stages

Strontium ranelate is a new antiosteoporotic treatment with a dual mode of action, both increasing bone formation and decreasing bone resorption, which rebalances bone turnover in favor of bone formation and increases bone strength. The antifracture efficacy of strontium ranelate, 2 g per day orally, in the treatment of postmenopausal osteoporosis has been investigated in a large-scale, international, multicenter, phase 3 program in which more than 7000 patients were recruited. This article deals with the vertebral antifracture efficacy of strontium ranelate in postmenopausal women with osteoporosis. A significant early (after 1 year) and sustained (over 3 years) antifracture efficacy of strontium ranelate, compared with placebo, was demonstrated in patients with prevalent vertebral fracture with reductions in risk of new vertebral fracture of 49% after 1 year ( P < 0.001) and 41% over 3 years ( P < 0.001). In addition, the relative risk of clinical vertebral fracture was significantly reduced by 52% ( P = 0.003) after 1 year and by 38% ( P < 0.001) over 3 years in the strontium ranelate group compared with placebo. Strontium ranelate was also demonstrated to significantly decrease the relative risk of vertebral fractures by 45% ( P < 0.001) in patients without prevalent vertebral fracture over 3 years, vs. placebo. Bone mineral density was linearly increased during 3 years of treatment with strontium ranelate in comparison with placebo. Strontium ranelate was well tolerated throughout the entire duration of the clinical trials. Thus, strontium ranelate, 2 g per day orally, is a new, effective, and safe treatment for postmenopausal patients with osteoporosis, to reduce the vertebral fracture risk in patients with or without a history of vertebral fracture.

Strontium Ranelate

Currently available medications, such as bisphosphonates, selective estrogen receptor modulators, and teriparatides, have shown their ability to reduce vertebral and/or nonvertebral fractures. Questions remain regarding their long-term innocuousness and several studies showed that adhering to currently marketed anti-osteoporotic medications remain sub-optimal. There is, therefore, an urgent need for the development of new effective, safe, and user-friendly medications to optimize the treatment of postmenopausal osteoporosis. The current review was designed to assess, through an extensive literature search, the antifracture efficacy of strontium ranelate on the axial and appendicular skeleton. Two multinational Phase 3 clinical trials have shown its efficacy and safety in the treatment of postmenopausal osteoporosis. In the Spinal Osteoporosis Therapeutic Intervention trial, strontium ranelate (2 g/day) treatment reduced the relative risk of a new vertebral fracture by 41% after 3 years compared with placebo. Data from the Treatment of Peripheral Osteoporosis study showed a 16% reduction in the relative risk of nonvertebral fracture in all patients and a 36% reduction in hip fracture in high-risk patients. Strontium rane-late reduces the risk of all fragility fractures and is well tolerated, which makes it a new first-line alternative in the treatment of postmenopausal osteoporosis. Therapeutic study, Level II (lesser quality randomized controlled trial [eg, < 80% followup, no blinding, or improper randomization]). See the Guidelines for Authors for a complete description of the levels of evidence.

Clinical effects of strontium ranelate in women with postmenopausal osteoporosis

Postmenopausal osteoporosis has long-term physical, psychological, and social consequences with a major impact on patients' daily life. Treatment for such a chronic disease needs to be clinically effective and well tolerated, and should ultimately result in a beneficial effect on quality of life. The antifracture efficacy of strontium ranelate, 2 g/day orally, an agent that appears to have dissociation effects on resorption and formation, has been assessed in two large, randomized, double-blind, placebo-controlled clinical studies: the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial and the TReatment Of Peripheral Osteoporosis Study (TROPOS), including more than 6,700 postmenopausal women. Pending the results of TROPOS, a 3-year analysis of SOTI results shows that strontium ranelate significantly reduces new vertebral and clinical vertebral fracture incidence in postmenopausal osteoporotic women. This significant reduction in the risk of clinical and new vertebral fractures has been demonstrated as early as after 1 year of treatment (RR = 0.48, p = 0.003; and RR = 0.51, p < 0.001, respectively) and is maintained over 3 years (RR = 0.62, p < 0.001; and RR = 0.59, p < 0.001, respectively). This is accompanied by decreased back pain and body height loss in the strontium ranelate group compared with the placebo group. As strontium ranelate appears to improve clinical signs and is, furthermore, well tolerated especially in the upper gastrointestinal region, this treatment is expected to result in an improved health-related quality of life (HRQoL). Strontium ranelate thus offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal women with vertebral osteoporotic fractures.

Prevention of vertebral fractures by strontium ranelate in postmenopausal women with osteoporosis.

The antifracture efficacy of strontium ranelate, a compound with a novel mechanism of action on bone, has been assessed in two large, randomized, controlled trials conducted in postmenopausal women. Strontium ranelate was given at a daily dose of 2 g, and all women received calcium and vitamin D supplements. In women with established osteoporosis there was a 41% reduction in vertebral fractures over 3 years' treatment [relative risk (RR) 0.59; 95% confidence interval (CI) 0.48-0.73; P<0.001]; significant reductions were also seen after only 1 year of treatment. The beneficial effect was also seen for clinical vertebral fractures: over 3 years there was a significant reduction in new clinical vertebral fractures (RR 0.62; 95% CI 0.47-0.83; P<0.001); this reduction was also observed during the first year of treatment (RR 0.48; 95% CI 0.29-0.80; P=0.003). Over the 3-year treatment period significantly fewer patients had height loss and fewer patients reported new or worsening back pain in the treated group than in the control group. These results demonstrate that strontium ranelate is a new therapeutic option in the prevention of osteoporotic vertebral fractures in postmenopausal women.