Strontium ranelate is a pharmaceutical compound once used to treat severe osteoporosis, a condition characterized by weakened bones and an elevated risk of fractures. This medication was primarily intended for postmenopausal women and men at high risk for bone fractures. Its application has become significantly restricted over time due to considerable safety concerns.
How Strontium Ranelate Works
Strontium ranelate operates through a distinct mechanism of action, setting it apart from other osteoporosis treatments. The drug influences bone metabolism by simultaneously stimulating bone-forming cells, known as osteoblasts, and inhibiting bone-resorbing cells, called osteoclasts. This dual effect helps to rebalance the continuous process of bone turnover, promoting the formation of new bone tissue while reducing the breakdown of existing bone.
The compound enhances osteoblast precursor cell replication and differentiation, increasing mature osteoblasts for new bone matrix production. It also increases the synthesis of collagen and other bone extracellular matrix proteins, contributing to bone architecture and strength. Concurrently, it reduces osteoclast differentiation and activity, which break down bone tissue. This rebalancing preserves and increases bone mass, improving bone microarchitecture and strength.
Associated Health Risks
Strontium ranelate has been linked to several serious health risks, which have led to significant limitations on its use. These concerns include an increased risk of cardiovascular events, venous thromboembolism, and a severe skin reaction known as DRESS syndrome. Healthcare professionals now carefully assess these risks before considering strontium ranelate for patients.
An increased risk of serious cardiovascular problems, including myocardial infarction, has been identified in patients taking strontium ranelate. Clinical trials involving approximately 7,500 postmenopausal women showed an increased incidence of myocardial infarction compared to placebo. Health authorities have since advised against its use in individuals with a history of ischemic heart disease, peripheral arterial disease, or cerebrovascular disease, or those with uncontrolled hypertension.
The medication has also been associated with a heightened risk of venous thromboembolism (VTE), which involves blood clot formation, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). Phase III clinical trials identified this association, leading to new contraindications for patients with a history of VTE or immobilization. While some observational studies have not consistently reported an increased VTE risk, the initial clinical trial data prompted regulatory warnings.
A rare but potentially fatal adverse reaction known as DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) has also been reported with strontium ranelate. This severe hypersensitivity reaction is characterized by a widespread skin rash, fever, enlargement of lymph nodes, and involvement of internal organs such as the liver. Symptoms typically appear two to six weeks after starting the medication, and can include eosinophilia and liver damage. A rash in a patient receiving strontium ranelate should prompt immediate and permanent discontinuation due to the seriousness of this condition.
Global Regulatory Standing
The significant health risks associated with strontium ranelate have directly influenced its regulatory status worldwide. The European Medicines Agency (EMA) initially approved strontium ranelate in 2004 for treating postmenopausal osteoporosis. However, as safety data emerged, particularly concerning cardiovascular risks, the EMA initiated reviews that led to severe restrictions on its use.
In 2013 and 2014, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended significant limitations, advising that strontium ranelate should only be used in severe cases of osteoporosis where other approved treatments are not suitable due to contraindications or intolerance. Strontium ranelate was never approved by the U.S. Food and Drug Administration (FDA) for use in the United States. The manufacturer, Servier, has since voluntarily withdrawn the drug from markets in many countries, though it briefly returned to the market in the United Kingdom in 2019 under a new name.
Other Osteoporosis Medications
For individuals diagnosed with osteoporosis, several other medication classes are commonly used as alternatives to strontium ranelate. Bisphosphonates are frequently the first-line treatment, working by slowing down bone loss. Examples include alendronate, risedronate, ibandronate, and zoledronic acid. These are available in various forms, including daily, weekly, or monthly oral pills, and annual intravenous infusions.
Another option is denosumab, a RANK ligand inhibitor, administered by injection every six months, which also works to prevent bone resorption. Anabolic agents like teriparatide and abaloparatide stimulate new bone formation, typically via daily injections for a limited duration. Romosozumab also increases bone formation and decreases bone resorption. Additionally, selective estrogen receptor modulators (SERMs) like raloxifene mimic estrogen’s beneficial effects on bone density in postmenopausal women.