New strategies for osteoporosis patients previously managed with strontium ranelate

Abstract

Abstract:The aim of this article is to describe potential alternatives to patients no longer eligible for management with strontium ranelate for osteoporosis according to the recommendations by the European Medicines Agency. A systematic search of Pubmed was done for papers on fracture efficacy of various treatments for osteoporosis, and potential harms especially in terms of cardiovascular events and stroke. The results showed that drugs more efficacious in terms of relative risk reduction of fractures than strontium ranelate were alendronate, risedronate, zoledronate, and denosumab. Raloxifene, as for strontium, may be associated with an increased risk of deep venous thromboembolism and fatal stroke. In terms of cardiovascular events special attention may be given to calcium supplements. Thus, patients at risk of stroke and ischemic cardiac events such as acute myocardial infarction should not use strontium ranelate. Ideally more efficacious drugs in terms of fracture reduction should be used such as alendronate, risedronate, zoledronate or denosumab. Raloxifene may pose a special problem as this too may be associated with an increased risk of fatal strokes. Other less-potent drugs in terms of fracture reduction should only be used if no alternatives are available (ibandronate, pamidronate, clodronate). Parathyroid hormone or analogs may be used for a limited time interval in specially selected patients and needs to be followed up with antiresorptive treatment to prevent loss of the bone gained. However, it should be remembered that no head-to-head comparison studies exist.

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

“…Therefore, caution is recommended in the prescription of the drug to patients with uncontrolled hypertension, history of ischemic heart disease, peripheral arterial disease, and cerebrovascular disease. In such situations, the use of bisphosphonates such as alendronate, risendronate, and zolendronate ( 24 , 52 , 53 ) are better options. In terms of relevance, as calcium plays a key role in the electrophysiology of the cardiac muscle and electrocardiographic abnormalities are known consequences of the plasma variations of this element, strontium has a potential arrhythmogenic effect ( 54 ).…”

Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model

“…Oral administration of strontium ranelate for the treatment of osteoporosis was approved for a long time [53]. Nevertheless, the oral application of strontium ranelate increases the risk of deep venous thromboembolism due to systemic distribution and, therefore, should be avoided in patients with an increased risk of stroke and ischemic cardiac disease [24]. To explore the positive effects of strontium, many reports have focused on the local application of Sr as single-ion substitutions in the scaffolds [54][55][56][57].…”

“…Experimental and clinical studies refer to some beneficial effects of strontium ranelate in the turnover of abnormal (and, in particular, of osteoporotic) bone, including increased osteogenesis and bone formation, as well as reduced fracture incidence, even when administered systemically by oral application [22,23]. Nevertheless, the oral application of strontium ranelate increases the risk of deep venous thromboembolism due to systemic distribution and, therefore, should be avoided in patients with the increased risk of stroke and ischemic cardiac disease [24]. The exact mechanism behind the action of strontium still needs to be elucidated [25,26].…”

Low-dose strontium stimulates osteogenesis but high-dose doses cause apoptosis in human adipose-derived stem cells via regulation of the ERK1/2 signaling pathway

“…However, SrRan is implicated in venous thromboembolism (VTE) and the risk of non-fatal myocardial infarction in women with postmenopausal osteoporosis [ 11 ]. Moreover, SrRan has been associated with significantly greater risk of death and cardiovascular risk compared with other osteoporotic drugs [ 12 ]. Thus, we should study the safety of SrRan with respect to osteogenic differentiation of ASCs.…”