Carotid Stenosis under Strontium Ranelate

Strontium ranelate (RS) occupies a place in the therapeutic arsenal of osteoporosis. It has been granted Marketing Authorization (MA) for the treatment of postmenopausal osteoporosis since January 2006. Its anti-fracture efficacy is at least equal to that of bisphosphonates. If some side effects are frequent and not severe, the serious risks of venous thromboembolism and DRESS are less frequent. Arterial accidents are exceptional. We report a case of internal carotid artery stenosis that occurred three years after treatment with strontium ranelate in a 76-year-old woman treated for non-active rheumatoid arthritis. Indeed in view of the side effects, RS was suspended.


Introduction
Osteoporosis is a generalized skeletal disorder characterized by low bone mass and deterioration of the microarchitecture of bone tissue, leading to bone fragility. In Morocco, it is estimated that 35% of women over the age of 50 are osteoporotic. Its gravity is the risk of fracture. Stontium Ranelate (RS) has been marketed in Morocco since 2007. It is involved in reducing the risk of vertebral fractures and hip fractures. Given its tolerance, it is mainly indicated, apart from male osteoporosis, in case of allergy or contraindications / 1 st hour, the C-reactive protein 8 mg / l, the composite activity index of rheumatoid arthritis (DAS 28) was at 2.69. The hemogram, hemostasis exploration balance, and electrophoresis of plasma proteins were normal. The rest of the metabolic exploration checkup, especially the blood sugar was correct. The drug origin of the thrombosis required discontinuation of strontium Ranelate.
The patient was placed on unfractionated heparin and platelet antiaggregant, with close monitoring. The clinical course was good (disappearance of the cervical swelling), the ultrasound control was normal, with receding at 25 months.

Figures 1 & 2:
Echodoppler of the jugulo-carotidian axes: Stenosis of the left internal carotid artery of 75% and right carotid thrombosis from its origin with very damped flows.

Discussion
Strontium Ranelate is composed of 2 stable strontium atoms and ranelate salt. It is the only anti-osteoporotic agent capable of positivering bone balance and at remodeling sites by combining bone formation and reduction of osteoclastic resorption [1].
It is indicated in postmenopausal osteoporosis [2], and in the prevention or recurrence of fractures [3,4]. It represents a therapeutic alternative in case of contraindication or intolerance to bisphosphonates [5,6]. Nevertheless, some adverse effects are attributed to treatment, the risk of venous thromboembolism and DRESS (being) which was the most severe. The annual incidence reported in the regional pharmacovigilance center registry is 2.7% with strontium ranelate versus, 1.9% with placebo, and a relative risk of 1.42 [7]. A French study showed that venous thromboembolic events (VTEA) were the main cardiovascular adverse events (93/104) with an incidence at 1/31 052 months of treatment, with deep vein thrombosis (54%), embolism pulmonary (34%), and 2% thrombosis of the central vein of the retina. At least one risk factor for venous thrombosis was found in 28% of patients [5]. In the same study, 6% of cerebrovascular accidents and transient ischemic attacks, and 1% of central retinal artery thrombosis were reported. A cohort of English general practitioners [8] attributed cardiovascular risk to older age, and osteoporosis rather than to RS. The relative risk of stroke was 1.75 in untreated osteoporotic women as in non-osteoporotic women, with a similar risk under Alendronate. This risk also existed with raloxifene and bisphosphonates in a Danish cohort [9] and in randomized, observational studies [10]. Additional biochemical studies aimed at investigating the relationship between thromboembolic risk and SR which did not show any changes in the biological parameters of hemostasis before and after two months of treatment [11,12]. In addition, a study in 45 patients treated for three months with RS found a decrease in the concentration of homocysteine [13]. Presence of added risk factors for vascular thrombosis was found in our patient: advanced age, rheumatoid arthritis. This does not venous thromboembolic side effects and probably arterial strontium ranelate accidents can be life-threatening. The physiopathogenic link is still heterogeneous. The rationalization of its prescription and regular monitoring of patients is essential. In the future, we hope that epidemiological studies may lead to comprehensive data analyzes on adverse effects under the latter.

Conflicts of Interest
None.