rred. Therapeutic relay may be considered whenever the benefit-risk balance is no longer deemed to be as favorable as at the beginning of menopause and/or after several years of use.

The occurrence of thrombosis during treatment is a contraindication, especially in patients with a history of thromboembolism.

The concomitant use of platelet aggregation inhibitors to prevent the risk of thrombotic injury is not associated with a change in thromboembolic risk. There was no significant difference between the two groups in the RUTH assay (HR 1.44, 95% CI 0.98, 2.10) and (HR 1.37, 95% CI 0.83, 2.27) (p = 0.88) [22] .

3.3. Strontium Ranelate

Strontium ranelate (RS) consists of 2 stable strontium atoms and ranelate salt. At the bone level, its mechanism of action is twofold: It acts on both osteoformation and resorption. Its anti-fracture efficacy has been widely demonstrated in clinical trials in patients naive to any antiosteoporotic treatment [23] . It is indicated in postmenopausal osteoporosis, in the prevention or recurrent fracture, and it represents a therapeutic alternative in case of contraindication or intolerance to bisphosphonates [24] . The optimal duration of treatment is 8 years.

However, some side effects may be associated, including venous thromboembolism and DRESS. The annual incidence reported in the regional pharmacovigilance center registry is 2.7% with strontium ranelate versus 1.9% with placebo, a relative risk of 1.42 [25] . Similarly, in the French study of Annie-Pierre et al. [26] Among cardiovascular adverse events, venous thromboembolic events were greater (93/104), deep vein thrombosis (54%), pulmonary embolism (34%), and 2% central vein thrombosis. of the retina. At least one risk factor for venous thrombosis was found in 28% of patients.

To explain their mechanisms of vascular action, some studies found a decrease in the concentration of homocysteine after treatment with RS, others did not find changes in the biological parameters of hemostasis, before and after two months of treatment [27] [28] .

Preventive Approaches under Strontium Ranelate

The French Agency for Health Safety of Health Products (AFSSAPS) and the Poison Control and Pharmacovigilance Center had issued a warning regarding the use of SR. The Transparency Committee re-evaluated this medicine on May 11, 2011 [29] . The indication was thus restricted to patients under 80 years of age, not immobilized with a contraindication/intolerance to bisphosphonates, without risk factors for venous thromboembolic events (ATEV).

Despite the low risk of reported venous thromboembolism, the benefit-risk balance has recently been re-evaluated by the European Medicines Agency. Thus, RS should not be prescribed in patients with a history of venous thromboembolic disease or in elderly patients at risk for venous thrombosis. A warning must also be given regarding the risk of hypersensitivity syndrome (or DRESS syndrome) and the appearance at the beginning of treatment of a generalized rash associated with a fever must lead to its arrest and to a specialized opinion [29] .

4. Conclusions

Although they occupy a place in the therapeutic arsenal of osteoporosis, with an efficiency close to that of bisphosphonates, the anti-osteoporotic drugs potentially associated with venous thromboembolic disease are: The hormonal treatment of menopause, selective osteogenic receptor modulators and strontium ranelate. The physiopathogenic link between these and the thrombotic risk is still heterogeneous. Despite their bone benefit, increasing evidence suggests that patients with VTE will be at greater risk for subsequent arterial events. In the future, we hope that epidemiological studies in outpatient and inpatient medicine may lead to more comprehensive analyzes of the undesirable effects of these drugs, the rationalization of their prescription and the vigilant monitoring of patients.

1) What is known about this topic

- Osteoporosis is a real public health issue, linked to the increase in morbidity and mortality.

- The therapeutic decision is based on the individual risk of fracture, the effectiveness and the degree of the therapeutic tolerance.

The anti-osteoporotic drugs potentially associated with thromboembolic venous disease are: Menopausal hormone therapy, selective oestrogenic hormone modulators and strontium ranelate.

2) What the study brings back

- The benefit and risk ratio of prescribed drugs can only be optimized by choosing the right time and the right treatment.

- Despite their bone benefit, recent, growing evidence suggests that patients with VTE may be at higher risk for subsequent events.

- The knowledge of the thromboembolic risk, the usual precautions of prescription and follow-up must be integrated in the strategies of the long-term care of the osteoporotic patients.

Authors’ Contributions

Kawtar Nassar: The author; Wafae Rachidi, Saadia Janani, Ouafa Mkinsi: Co-authors.

Abbreviation Note List

NIH: National Institue of Health

WHO: World Health Organisation

THM: Hormone Therapy in Menopause

WHI: World Health Institue

VTE: Venous Thromboembolism

SERMs: Selective Estrogen Receptor Modulators

BMD: Bone Mineral Density

RS: Stontium Ranelate

AFSSAPS: The French Agency for Health Safety of Health Products

DRESS: Drug Reaction with Eosinophilia and Systemic Symptoms

Cite this paper
Nassar, K. , Rachidi, W. , Janani, S. and Mkinsi, O. (2018) Review Venous Thromboembolism Risk with Anti-Osteoporosis Drugs. Open Journal of Rheumatology and Autoimmune Diseases, 8, 111-119. doi: 10.4236/ojra.2018.84012.
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