Strontium ranelate

Overview
Strontium ranelate is a medication for osteoporosis marketed as Protelos or Protos by Servier. It is unusual in the sense that it both increases deposition of new bone osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).

Mode of action
Strontium ranelate is the only antiosteoporotic agent which both increases bone formation and reduces bone resorption, resulting in a rebalance of bone turnover in favor of bone formation. Strontium ranelate significantly reduces the risk of vertebral fractures in postmenopausal osteoporotic women with or without previous fractures, and also significantly reduces the risk of hip fractures.

Strontium ranelate stimulates the calcium sensing receptors and leads to the differentiation of pre-osteoblast to osteoblast which increases the bone formation. Strontium ranelate also stimulates osteoblasts to secrete osteoprotegerin in inhibiting osteoclasts formed from pre-osteoclasts in relation to the RANKL system, which leads to the decrease of bone resorption.

Indication
Strontium ranelate is registered in more than 70 countries for the treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures. Most of the guidelines recommend strontium ranelate as the first line antiosteoporotic drug.

2 major phase III clinical studies, SOTI (Spinal Osteoporosis Therapeutic Intervention)and TROPOS (Treatment of Peripheral Osteoporosis), were started to undergo in 2000 to investigate the efficacy of strontium ranelate in reducing vertebral fractures and peripheral fractures, including hip fractures. In the 3 years results, strontium ranelate showed significant reduction in vertebral fractures with 41% and hip fractures with 36% compared with patients treated with placebo. Moreover, the efficacy sustained in 5 years data.

Furthermore, the 5 years data confirmed that strontium ranelate can reduce the vertebral fractures significantly no matter the risk factors of the osteoporotic women have. These include their age (<70, 70-80 and >80), bone mineral density (osteoporotic and osteopenia), prevalent fractures (0 prevalent fracture, 1-2 prevalent fractures and >2 prevalent fractures), symptomatic fractures, body mass index and smoking.

Compared with other antiosteoporotic agents, strontium ranelate is the only one which has the long term hip fracture data, shows antifracture efficacy in very old elderly and osteopenic patients. And strontium ranelate is very well tolerated.

Presentation and composition
Each sachet contains 2 g of strontium ranelate.

Dosage
One sachet daily at bedtime diluted in a glass of water.

Contraindications
Strontium ranelate is contraindicated in hypersensitivity to the active substance or to any of the excipients. It is not recommended in patients with severe renal disease, i.e. creatinine clearance below 30 mL/min due to lack of data. Precaution is advised in patients at increased risk of venous thromboembolism (VTE), including patients with a past history of VTE. Precaution is advised in patients with phenylketonuria, as strontium ranelate contains phenylalanine.

Interactions
According to the manufacturer, strontium ranelate should be taken 2 hours apart from food, milk and derivative products, and medicinal products containing calcium. Should be taken 2 hours before antacids. Treatment should be suspended while taking oral tetracycline and quinolone antibiotics, as these chelate the active substance.

Side effects
The most common side effects include nausea, diarrhea, headache and eczema, but with only 2–4% increase compared with placebo group. However, most of the side effect will be tolerated in 3 months.