Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Protos (Servier)
sachets containing 2 g granules for oral suspension
Approved indication: postmenopausal osteoporosis
Australian Medicines Handbook section 10.3

Strontium is an element which was used in the past to treat osteoporosis. It fell out of use because it was associated with defects in bone mineralisation. Strontium ranelate aims to overcome the problems associated with strontium.

Patients take 2 g of granules in water. As the slow absorption is reduced by food, the dose should be taken at bedtime at least two hours after eating. Binding in the gut can reduce the absorption of some antibiotics. Tetracyclines and quinolones should therefore not be taken with strontium ranelate.

When the molecule dissociates, the strontium is taken into bone. It is thought to stimulate osteoblasts to make bone and to decrease the resorption of bone by osteoclasts. Strontium is slowly released from bone and excreted by the gut and kidney. Clearance is reduced by renal disease. The half-life of strontium is approximately 60 hours.

Strontium ranelate was studied in 353 women with postmenopausal vertebral osteoporosis and a history of at least one vertebral fracture. These women were randomised to take different doses of strontium ranelate or a placebo for two years. They also took calcium and vitamin D. There was a rise in alkaline phosphatase activity and a dose-dependent increase in lumbar bone density in the women who took strontium ranelate.1

A subsequent trial enrolled 1649 postmenopausal women with a history of osteoporosis and at least one vertebral fracture. These women took calcium and vitamin D with either 2 g of strontium ranelate or a daily placebo. After three years the bone mineral density of the lumbar spine had increased by 6.8% in the women taking strontium ranelate, but decreased by 1.3% in the placebo group. New vertebral fractures appeared on the X-rays of 20.9% of those taking strontium ranelate and 32.8% of those taking placebo. Symptomatic vertebral fractures occurred in 11.3% of the strontium group and 17.4% of the placebo group - a small, but statistically significant difference.2

Another study looked at the effect of strontium ranelate on non-vertebral fractures in 4932 elderly women with reduced bone density. Strontium increased bone density and over three years there was a 16% reduction in the relative risk of fractures. The absolute difference in fractures was small, with a cumulative incidence of 12.9% in the placebo group and 11.2% in the women taking strontium. There was only a 0.5% overall reduction in hip fractures over three years.3

Common adverse effects of strontium ranelate include headache, nausea and diarrhoea. Although the incidence is less than 1%, there is a higher risk of venous thromboembolism in patients taking strontium ranelate. Neurological problems such as altered consciousness or seizures occurred more frequently with strontium in placebo-controlled trials.

While serum calcium may fall during treatment, strontium can interfere with some of the laboratory assays used to measure calcium concentrations. At present there are limited histomorphometric data to assess the mineralisation of bone during treatment.

Based on the trial of the 2 g dose, nine patients, with osteoporosis and a history of fracture, would need to take strontium ranelate, calcium and vitamin D for three years to prevent one radiological fracture of a vertebra.2The reduction in the risk of vertebral fracture is similar to that seen with bisphosphonates, but the drugs do not seem to have been directly compared in published trials.

Read about The Transparency Score manufacturer provided additional useful information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.