The work carried out by the authors on calcium and the cardiovascular risk is of primary importance.¹ We thank the authors for questions and comments on the Strontium ranelate Efficacy in Knee OsteoarthrItis trIAl (SEKOIA) study, safety being a primary concern for us.²

The number of emergent adverse events reported in the SEKOIA study was similar in the three treatment groups: 85.8%, 87.9% and 86.5% in the SrRan 1g, SrRan 2g and placebo groups, as well as the number of serious emergent adverse events: 17.0%, 16.5% and 17.4%, respectively. The adverse reactions considered by the investigators as related to the study drug were similar to those reported in osteoporotic patients: diarrhoea (3.3%, 6.6% and 2.7%, respectively), nausea (2.0%, 2.7% and 1.8%, respectively), and headache (1.6% in each SrRan group and 0.7% in the placebo group). Regarding cutaneous safety, 16.3% of the patients reported skin disorders in the SrRan 2g group compared to 12.4% and 12.2% in the SrRan 1g group and in the placebo group, respectively, which is in line with the incidence of skin reactions in osteoporotic patients. No cases of drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) were reported.

When specifically focusing on cardiac safety, a similar incidence of cardiac events was reported in the three treatment groups: 5.5%, 5.7% and 5.8%, respectively. Five cases of serious myocardial infarction were reported in the 2g group while 1 case was reported in the SrRan 1g group and in the placebo group. All events occurred in patients with major cardiovascular risk factors or comorbidities. All patients were suffering from hypertension from several years, and all but one were overweight or obese. Among the patients treated with strontium ranelate, all presented additional risk factors, such as hypercholesterolaemia, diabetes, or previous or family myocardial ischaemia. Based on this small number of events and on the presence of numerous comorbidities, it seemed difficult at the time of the results to formally conclude a higher risk of myocardial infarction (MI) with SrRan. These results were then submitted to the European Medicine Agency and were part of the routine benefit-risk assessment of the strontium ranelate. When applying, a posteriori, the newly defined contraindications of the European Medicine Agency to the SEKOIA population (ie, when excluding patients with pathology at baseline corresponding to the newly defined contraindications: uncontrolled hypertension, thromboembolic events including deep vein thrombosis and pulmonary embolism, ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease), the number of MIs become comparable between the three treatment groups: one event in the SrRan 1g group, two in the SrRan 2g group and one in the placebo group, demonstrating that the contraindications are effective to minimise the cardiac risk in this population of osteoarthritis patients.