Is strontium ranelate effective for treating osteoporosis?

Strontium Ranelate for Osteoporosis

Strontium ranelate is an effective treatment option for postmenopausal osteoporosis that reduces both vertebral and non-vertebral fractures, but it should be considered a second-line or alternative therapy after bisphosphonates, particularly in patients who cannot tolerate or have failed first-line treatments. 1

Evidence for Efficacy

Vertebral Fracture Reduction

• Strontium ranelate 2 g daily reduces vertebral fracture risk by 41% over 3 years in postmenopausal women with prevalent vertebral fractures (P < 0.001). 2
• Early efficacy is demonstrated with a 49% reduction in new vertebral fractures after just 1 year of treatment (P < 0.001). 2
• In women without prevalent vertebral fractures, strontium ranelate reduces vertebral fracture risk by 45% over 3 years (P < 0.001). 2
• Clinical vertebral fractures are reduced by 38% over 3 years (P < 0.001). 2

Non-Vertebral and Hip Fracture Reduction

• In the general osteoporotic population, strontium ranelate reduces all non-vertebral fractures by 16% (P = 0.04) and major fragility fractures by 19% (P = 0.031) over 3 years. 3
• In high-risk patients (age ≥74 years with femoral neck T-score ≤-3), hip fracture risk is reduced by 36% (P = 0.046). 3
• A Cochrane review confirmed a 37% reduction in vertebral fractures (RR 0.63,95% CI 0.56-0.71) and 14% reduction in non-vertebral fractures (RR 0.86,95% CI 0.75-0.98) with 2 g daily. 4

Bone Mineral Density Effects

• Strontium ranelate increases lumbar spine BMD by approximately 3% annually and femoral neck BMD by 8.2% at 3 years (P < 0.001). 5, 3
• Total hip BMD increases by 9.8% at 3 years (P < 0.001). 3

Position in Treatment Algorithm

Current Guideline Recommendations

• The 2022 ACR guideline for glucocorticoid-induced osteoporosis lists strontium ranelate as a treatment option for patients who are unable to tolerate alendronate or risedronate, requiring specialist referral. 1
• The 2023 ACP guideline does not specifically recommend strontium ranelate as a first-line option, prioritizing bisphosphonates instead. 1
• European guidelines from 2013 support the use of strontium salts with Level 2a evidence, Grade B recommendation for postmenopausal women with osteoporosis. 1

Appropriate Patient Selection

• Consider strontium ranelate for postmenopausal women with established osteoporosis who cannot tolerate oral bisphosphonates due to gastrointestinal side effects. 1
• Use in patients requiring alternatives to bisphosphonates, particularly those with contraindications to oral bisphosphonates (such as esophageal disorders or concerns about varices). 1
• For patients with acute osteoporotic vertebral compression fractures, strontium ranelate is recommended to prevent additional symptomatic fractures. 6

Safety Profile and Important Caveats

Common Adverse Effects

• Diarrhea is the most common side effect, occurring more frequently than placebo, though it does not significantly increase treatment discontinuation rates. 4
• Adverse event rates overall are similar to placebo in clinical trials. 5, 2, 3

Serious Safety Concerns

• Strontium ranelate increases the risk of venous thromboembolism by approximately 50%, including pulmonary embolism. 7
• Increased serum creatine kinase activity occurs in 30% of patients. 7
• Recent data show increased cardiovascular risk with strontium ranelate, which has led to restricted use in some regions. 1
• Potential neurological and muscular adverse effects require monitoring, though these were inadequately documented in trials. 7

Long-Term Safety Unknowns

• The long-term effects on bone quality (osteomalacia, pathological fractures) remain unknown, particularly concerning given historical issues with high-dose strontium use in the 1950s causing bone mineralization disorders. 7
• Data from dialysis patients raise concerns about potential bone toxicity with prolonged use. 7

Dosing and Administration

Standard Dosing

• The effective dose is 2 g daily orally for treatment of established osteoporosis. 5, 2, 3
• Lower doses (0.5 g, 1 g) show inferior efficacy compared to 2 g daily. 4, 5
• All patients should receive concurrent calcium and vitamin D supplementation. 5, 3

Duration of Treatment

• Efficacy is demonstrated over 3 years of continuous treatment. 2, 3
• Early benefits appear within the first year of treatment. 2

Mechanism of Action

• Strontium ranelate has a unique dual mode of action: it increases bone formation by stimulating osteoblast activity while simultaneously decreasing bone resorption by inhibiting osteoclast activity. 5, 2
• This rebalances bone turnover in favor of bone formation, distinguishing it from pure antiresorptive agents like bisphosphonates. 5

Clinical Bottom Line

Strontium ranelate is an effective alternative for postmenopausal osteoporosis with proven vertebral and non-vertebral fracture reduction, but cardiovascular and thromboembolic risks limit its use to patients who cannot tolerate or have failed bisphosphonates. 1, 7 The 2 g daily dose should be used with calcium and vitamin D supplementation, and patients require monitoring for venous thromboembolism and cardiovascular events. 7, 4 Given the superior safety profile and more extensive evidence base for bisphosphonates, strontium ranelate should be reserved for second-line therapy after specialist consultation. 1