Treatment Of Peripheral Osteoporosis Research Articles

A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis.

Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS(®)) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis.

Risk of nonvertebral fractures among elderly postmenopausal women using antidepressants

ObjectiveTo examine the association between antidepressants, including TCAs, SSRIs, and miscellaneous antidepressants and the risk of nonvertebral fractures among women with osteoporosis. Materials and methodsThis study was a post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]). A nested case‐control study was performed in the placebo treated population. Adjusted logistic regression models were used to estimate the risk of nonvertebral fracture associated with the use of antidepressants. ResultsAfter 3years of follow-up, 391 nonvertebral fractures cases were identified and matched to 1955 controls. Compared with non-users of antidepressants, antidepressants use was associated with an increased risk of nonvertebral fractures (adjusted OR=1.64; 95%CI, 1.03–2.62]). Particularly, there was a 2-fold risk increase (95%CI, 1.07–3.79) of nonvertebral fracture for current users of SSRIs and a 2.1-fold risk increase for subjects who were current users of TCAs (95%CI, 1.02–4.30). Among patients categorized as recent or past users, none of the classes of antidepressants were statistically associated with increased risk of nonvertebral fracture. ConclusionsOur findings confirm that both SSRIs and TCAs increase the risk of nonvertebral fracture in current users.

Treatment of Postmenopausal Osteoporosis: Focus on Strontium Ranelate

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR), a new anti-osteoporotic treatment with a unique mode of action, has been investigated in the Spinal Osteoporosis Therapeutic Intervention (SOTI) and the Treatment Of Peripheral OSteoporosis (TROPOS) trials, two major 3-year multinational placebo-controlled Phase III randomized clinical trials. In SOTI, SR treatment reduced the risk of vertebral fracture by 41% (20.9% vs. 32.8%, P < 0.001); in TROPOS, it reduced the risk of non-vertebral fracture by 16% (11.2% vs. 12.9%, P = 0.04), and the risk of hip fracture in patients at high risk by 36% (4.3% vs. 6.4%, P = 0.046). Also SR has been shown to decrease the risk of vertebral fracture after 4 years of treatment and the risk of nonvertebral fracture after 5 years. Also it demonstrated for high risk patients a significant decrease of the risk of hip fractures (–43%) after 5 years of treatment. Unlike antiresorptive agents, SR produced steady and significant BMD increases that correlated directly with decreases in vertebral and hip fracture risk. Preplanned analysis of the pooled dataset from SOTI and TROPOS showed that SR was effective whether or not patients had key risk factors for fractures at baseline. SR was also effective in patients with osteopenia and younger postmenopausal patients aged 50–65 years. It was also effective for preventing both vertebral and nonvertebral fractures in the elderly (>80 years). Also, SR significantly attenuated height loss and decreased back pain. Finally long-term follow-up showed that BMD gains were maintained through a 8 year-period with maintaining the incidence of fracture between the first 3 years and the last 3 years of treatment. The safety profile of SR was almost similar to placebo in both trials. A slight but significant increased risk of thromboembolism events was noted from the pooled phase III studies data. However this increased was not found in a large retrospective observational study. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and non-vertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease, and their risk factors.

Use of Strontium as a Treatment Method for Osteoporosis

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR), a new anti-osteoporotic treatment with a unique mode of action, has been investigated in the SOTI (Spinal Osteoporosis Therapeutic Intervention) and the TROPOS (Treatment of Peripheral Osteoporosis) trials, two major 3-year multinational placebo-controlled phase 3 randomized clinical trials. Unlike antiresorptive agents, SR produced steady and significant bone mineral density increases that correlated directly with decreases in vertebral and hip fracture risk. The safety profile of SR was almost similar to placebo in both trials. A slight but significant increased risk of thromboembolism events was noted from the pooled phase 3 studies data. However, this increased was not found in a large retrospective observational study. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and nonvertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease, and their risk factors.

Strontium ranelate and risk of vertebral fractures in frail osteoporotic women

Aim Therapies to treat osteoporosis remain underutilized and minimally evaluated in frail elderly patients. Our study determined and compared the risk of vertebral fractures in frail, intermediate and robust older patients being treated with strontium ranelate vs. placebo. Methods Data were obtained from the SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment Of Peripheral Osteoporosis) studies which randomized participants to receive either strontium ranelate or placebo over 3 years. Frail, intermediate and robust patients were identified using adapted Fried's criteria. Analyses were performed according to the intention-to-treat principle utilizing 1- and 3-year study follow-up data. Results 2346 robust, 2472 intermediate and 264 frail women were identified. At 3 years, the risk for vertebral fractures was reduced by 30% (Relative Risk [RR], 0.70; 95% confidence interval [CI], 0.57-0.86) in the robust, by 45% (RR, 0.55; 95%CI, 0.46-0.67) in the intermediate and by 58% (RR, 0.42; 95%CI, 0.24-0.74) in the frail patients compared to those assigned to placebo ( p < 0.01 for all three groups; p = 0.11 for trend). Risk of vertebral fracture was significantly reduced within 1 year in all three groups. Numbers of subjects needed to be treated to prevent one new vertebral fracture over 3 years were 13, 9 and 5 in the robust, intermediate and frail groups, respectively. Adverse event profiles and medication compliance were similar across the 3 groups. Conclusions The imperative to treat osteoporosis appears to be greatest in frail patients since similar relative risk reductions would avert more fractures in frail than in non-frail elderly patients.

Prospective assessment of thoracic kyphosis in postmenopausal women with osteoporosis

We attempt to assess quantitatively thoracic kyphosis and its influence on incident fractures and quality of life over three years in postmenopausal women with osteoporosis and the effect of strontium ranelate on thoracic kyphosis progression. This study was performed on women with postmenopausal osteoporosis from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and Treatment of Peripheral Osteoporosis (TROPOS) studies. Vertebral fractures were assessed on lateral thoracic radiographs performed at baseline and at three years according to standardized procedure. Kyphosis index (KI, %), was defined as the percentage ratio between the maximum depth of thoracic curvature and the height measured from the T4 to the T12 vertebrae. Baseline characteristics of the 3218 patients (1594 strontium ranelate, 1624 placebo) were mean age 73.3 years, spine bone mineral density (BMD) T-score (L2-4) -3.1, femoral neck T-score -3.0, and KI 25.4%. In the placebo group, patients with the highest baseline KI experienced significantly more vertebral fractures than those with medium KIs [relative risk (RR) = 1.53; 95% confidence interval (CI) 1.19-1.96, p < .001) or the lowest KIs (RR = 1.70, 95%CI 1.32-2.21, p < .001), even after adjusting for the presence of prevalent fractures, age, body mass index (BMI), and BMD. There was no difference in the risk of nonvertebral fractures according to baseline KI. Three-year changes in quality-of-life physical scores reflected significantly better status for patients in the lowest tertile of KI compared with those in the highest at baseline. Over three years, the KI increased for all patients, indicating worsening of thoracic kyphosis, whatever the presence of prevalent or incident vertebral fractures. This KI progression was lower in the strontium ranelate group than in the placebo group. Thoracic kyphosis is a risk factor for vertebral fractures over three years and influences physical capacity changes in postmenopausal women with osteoporosis. Thoracic kyphosis progression over three years is lower in a subgroup of strontium ranelate-treated patients compared with placebo-treated patients.

Positive impact of compliance to strontium ranelate on the risk of nonvertebral osteoporotic fractures

Adherence is now one of the major issues in the management of osteoporosis. This paper relates the relationship existing between adherence to strontium ranelate and the risk of subsequent nonvertebral fracture among postmenopausal women with osteoporosis. The aim of this study is to investigate compliance to strontium ranelate (SR) therapy and the impact of compliance on the risk of nonvertebral fractures among women with osteoporosis. This study was a post-hoc analysis of pooled data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention and Treatment Of Peripheral Osteoporosis). A nested case-control study was performed in the strontium ranelate-treated population. Compliance was quantified using the medication possession ratio (MPR). Two hundred eighty-five nonvertebral fracture cases (hip fx n = 70; major nonvertebral fx n = 213) were identified and matched to 1,425 controls. The mean MPR was 86.8% for controls and 82.6% for cases (p < 0.001). Women who were compliant to SR had a 38% reduction in all nonvertebral fractures compared with those who were not (OR = 0.62; 95%CI[0.47-0.81; p < 0.001). Considering hip fractures only, the risk was reduced by 50% for compliant patients compared to noncompliant patients (OR = 0.50; 95%CI[0.28-0.88]; p < 0.05). Our analyses emphasize the importance of good compliance to treatment in order to reduce the risk of osteoporotic fractures. In particular, there was a greater reduction in the risk of nonvertebral and hip fractures with increase compliance.

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

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.

Osteoporosis: from early fracture prevention to better bone health with strontium ranelate

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR) is an osteoporosis treatment with a unique mode of action, which was launched in 2004. It has been investigated in the Spinal Osteoporosis Therapeutic Intervention (SOTI) and the TReatment Of Peripheral OSteoporosis (TROPOS) trials, two major 3-year multinational placebo-controlled Phase III randomized clinical trials. In SOTI, SR treatment reduced the risk of vertebral fracture by 41% (20.9 vs 32.8%; P < 0.001); in TROPOS, it reduced the risk of non-vertebral fracture by 16% (11.2 vs 12.9%; P = 0.04) and the risk of hip fracture in patients at high risk by 36% (4.3 vs 6.4%; P = 0.046). Unlike anti-resorptive agents, SR produced steady and significant BMD increases that correlated directly with decreases in vertebral and hip fracture risk. Preplanned analysis of the pooled dataset from SOTI and TROPOS showed that SR was effective whether or not patients had key risk factors for fractures at baseline. SR was also effective in patients with osteopenia and younger postmenopausal patients aged 50-65 years. Finally, SR significantly attenuated height loss and decreased back pain. The safety profile of SR was almost similar to placebo in both trials. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and non-vertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease and their risk factors.

&lt;b&gt;Strontium Ranelate for the Management of Osteoporosis&lt;/b&gt;

To evaluate the role of strontium ranelate in the management of osteoporosis. A MEDLINE (January 1966 to May 2007) search using the terms osteoporosis, strontium ranelate, bonemineral density, and fractures. All English-language articles identified from the data sources were evaluated. Strontium ranelate stimulates bone formation and inhibits bone resorption. Its safety and efficacy for osteoporosis were evaluated in four prospective, randomized, double-blind, placebo-controlled trials. The PREVOS (Prevention of Early Postmenopausal Bone Loss by Strontium Ranelate) trial suggested that 1 g daily is the optimal dose for preventing postmenopausal bone loss and was associated with a 1.41% increase in lumbar bone-mineral density (BMD). However, the STRATOS (Strontium Administration for Treatment of Osteoporosis) study found that a 1 g daily regimen was associated with a higher incidence of new vertebral deformities, and a 2 g daily regimen reduced lumbar BMD by 3% in postmenopausal, osteoporotic women. The SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) studies suggested that a 2 g daily regimen reduced vertebral fractures by 39% to 41%, nonvertebral fractures by 16%, in postmenopausal, osteoporotic women. Most common adverse events reported were nausea and diarrhea. Four clinical trials demonstrated the efficacy and safety of strontium ranelate for the management of postmenopausal osteoporosis; however, the Food and Drug Administration has not approved it for this indication.

Strontium Ranelate Reduces the Risk of Vertebral Fractures in Patients With Osteopenia

Many fractures occur in women with moderate fracture risk caused by osteopenia. Strontium ranelate was studied in 1431 postmenopausal women with osteopenia. Vertebral fracture risk reduction of 41-59% was shown depending on the site and fracture status at baseline. This is the first report of antivertebral fracture efficacy in women with vertebral osteopenia. Women with osteoporosis are at high risk for fracture. However, more than one half of all fractures in the community originate from the larger population at more moderate risk of fracture caused by osteopenia. Despite this, evidence for antifracture efficacy in these persons is limited. The aim of this study was to determine whether strontium ranelate, a new drug that reduces fracture risk in women with osteoporosis, is also effective in women with osteopenia. Data from the Spinal Osteoporosis Therapeutic Intervention study (SOTI; n = 1649) and the TReatment Of Peripheral OSteoporosis (TROPOS; n = 5091) were pooled to evaluate the antivertebral fracture efficacy of strontium ranelate in women with lumbar spine (LS) osteopenia with any BMD value at the femoral neck (FN; N = 1166) and in 265 women with osteopenia at both sites (intention-to-treat analysis). The women were randomized to strontium ranelate 2 g/d orally or placebo for 3 yr. No group differences were present in baseline characteristics that may influence fracture outcome independent of therapy. In women with LS osteopenia, treatment reduced the risk of vertebral fracture by 41% (RR = 0.59; 95% CI, 0.43-0.82), by 59% (RR = 0.41; 95% CI, 0.17-0.99) in the 447 patients with no prevalent fractures, and by 38% (RR = 0.62; 95% CI, 0.44-0.88) in the 719 patients with prevalent fractures. In women with osteopenia at both sites, treatment reduced the risk of fracture by 52% (RR = 0.48; 95% CI, 0.24-0.96). Strontium ranelate safely reduces the risk of vertebral fractures in women with osteopenia with or without a prevalent fracture.

Effects of strontium ranelate on spinal osteoarthritis progression

Objective:The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA).Methods:This study was a post-hoc analysis of pooled...

Strontium ranelate in the prevention of osteoporotic fractures

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.

Strontium Ranelate

Strontium ranelate (SR) is a novel antiosteoporotic agent, electively concentrated in positions of active bone formation, and especially onto the crystal surface that allows permanent exchanges with extracellular fluid. Although the mechanism(s) of action is still under rigorous research, SR appears to reduce bone resorption by decreasing osteoclast differentiation and activity and to stimulate bone formation by increasing replication of preosteoblast cells, leading to increased matrix synthesis. In the placebo-controlled, phase III trial spinal osteoporosis therapeutic intervention (SOTI) (no=1442; mean age 69 years), there was a 41% decrease over 3 years in the number of patients with new vertebral fractures in the SR (2 g/day) group versus placebo (P<0.001), already detected after 12 months (49% lower risk, P<0.001). The phase III treatment of peripheral osteoporosis (TROPOS) study assessed the efficacy of SR (2 g/day) in preventing nonvertebral fractures in postmenopausal osteoporosis (no=4932; mean age 77 years). SR reduced nonvertebral fracture risk by 16% versus placebo (P=0.04) and hip fracture risk by 36% (P=0.031) in osteoporotic patients older than 74 years. Thus SR is an effective and safe treatment for vertebral and hip osteoporosis with a unique mode of action.

Strontium Ranelate Reduces the Risk of Vertebral and Nonvertebral Fractures in Women Eighty Years of Age and Older

Strontium ranelate produces an early and sustained reduction of both vertebral and nonvertebral fractures in patients > or = 80 years of age. About 25-30% of the population burden of all fragility fractures in the community arise from women > or = 80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women >50 years of age, also reduces fractures in the elderly. An analysis based on preplanned pooling of data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X-rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included. Baseline characteristics did not differ in placebo and treatment arms. In the intent-to-treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within 1 year by 59% (p = 0.002), 41% (p = 0.027), and 37% (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22% (p = 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients. Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis > or = 80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.

Protelos: Nonvertebral and hip antifracture efficacy in postmenopausal osteoporosis

Strontium ranelate is a new treatment for postmenopausal osteoporosis, simultaneously increasing bone formation and decreasing bone resorption, thus rebalancing bone turnover in favor of bone formation. Strontium ranelate was demonstrated to significantly reduce the relative risk of vertebral fracture whatever the severity of the disease. In the TReatment Of Peripheral OSteoporosis (TROPOS) study, the incidence of nonvertebral and hip fractures, following treatment with strontium ranelate (Protelos®, Servier) at a dosage of 2 g/day orally, was assessed over a 3-year period. In this double-blind, placebo-controlled trial, 5091 women with postmenopausal osteoporosis were assigned to either strontium ranelate ( n = 2479) or placebo ( n = 2453) treatment. Overall, the reduction in risk for nonvertebral fractures in patients treated with strontium ranelate was 16% ( P = 0.04) and for major fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle and humerus), it was 19% ( P = 0.031), compared with those treated with placebo. Women with osteoporosis and aged 74 years or more who were treated with strontium ranelate ( n = 982) had a 36% reduction in risk of hip fracture ( P = 0.046) over 3 years compared with those treated with placebo ( n = 995). The difference in bone mineral density between groups was 8.2% for femoral neck and 9.8% for total hip at 3 years. The incidence of adverse events was comparable between groups. The study demonstrates that strontium ranelate treatment offers a safe and effective means of reducing the risk of nonvertebral and hip fractures in postmenopausal women with osteoporosis.

Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women With Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women With Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women With Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Strontium ranelate is an orally active drug that may permit ongoing production of bone while at the same time reducing bone resorption. New vertebral fractures reportedly are less frequent in postmenopausal women who receive this agent. The Treatment of Peripheral Osteoporosis Study (TROPOS) is a randomized, double-blind, placebo-controlled trial designed to show whether strontium ranelate prevents nonvertebral fractures in European and Australian postmenopausal women who had a bone mineral density (BMD) equivalent to a T-score less than −2.5. Participants were 74 years or older, or 70 to 74 years if an additional fracture risk factor was present. Either strontium ranelate in a daily dose of 2 g or placebo was given to 5091 postmenopausal women with osteoporosis. Major statistical analysis was undertaken over 3 years of treatment. The intention-to-treat population totaled 4932 patients. The relative risk (RR) of nonvertebral fractures was reduced 16% during 3 years of follow up, and major nonvertebral osteoporotic factors were reduced by 19%. The RR for hip fracture was reduced by 15%—not a statistically significant result. Hip fractures were reduced 36% in women aged 74 years and older who had a BMD T-score of −3 or less. Patients given strontium ranelate had a 39% reduction in the RR of new vertebral fractures over 3 years. The RR of a first vertebral fracture was lowered by 45%. BMD increased significantly in both the total hip and femoral neck. Treatment was well-tolerated, and changes in serum levels of calcium, phosphorus, and parathyroid hormone were not of clinical importance. Nonvertebral fractures, particularly hip fractures, are significantly less likely to occur in postmenopausal women with osteoporosis who receive 2 g of strontium ranelate daily compared with placebo recipients. The investigators believe that this drug could be a helpful first-line treatment for postmenopausal osteoporosis.

Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.