Strontium: new drug. Postmenopausal osteoporosis: too many unknowns

(1) Strontium ranelate is marketed in the European Union for the treatment of postmenopausal osteoporosis. Strontium, a cation closely related to calcium, was already used for this purpose in the 1950s but was abandoned because it caused bone mineralization disorders (mainly due to the high doses used at the time). (2) Strontium has only been compared with placebo: there are no clinical trials versus a diphosphonate. (3) On the basis of bone mineral density, two dose-finding studies suggested that, in women who are also taking calcium and vitamin D, the effective minimal dose of strontium is 1 g/day for primary prevention and 2 g/day for secondary prevention. (4) In secondary prevention, a randomised, double-blind trial (SOTI) involving 1649 postmenopausal women who had already had an osteoporotic fracture and were also taking calcium + vitamin D, showed that 2 g strontium daily reduced the risk of symptomatic vertebral fractures compared with placebo (11.3% versus 17.4%) after three years of treatment. (5) Another randomised, double-blind trial (TROPOS) involved 5091 women with osteoporosis of the femur. After three years of treatment with calcium, vitamin D, and either 2 g/day strontium or placebo, the risk of non vertebral osteoporotic fracture was lower in the strontium arm (10.9% versus 9.1%; relative risk 0.85, 95% confidence interval 0.71-1.01), although the difference was only just significant (p = 0.05). This trial failed to show that strontium reduced the risk of femoral fracture. A retrospective subgroup analysis raised the possibility of a preventive effect on hip fracture in patients aged over 74 years, but again the difference had only borderline significance (relative risk 0.64, confidence interval 0.412-0.997). (6) The SOTI and TROPOS studies were subsequently pooled for analysis. A retrospective subgroup analysis of women aged over 80 suggested some efficacy on non vertebral fractures, but this remains to be confirmed in a comparative trial with relevant outcome measures. (7) The reports of these trials include little information on the adverse effects of strontium. Strontium caused a 50% increase in the risk of venous thromboembolism (including pulmonary embolism). Strontium also increased serum creatine kinase activity in 30% of patients. Strontium can affect mental functions, and this effect needs to be quantified. Neurological and muscular adverse effects were inadequately documented, although disorders of this type were observed in animals. (8) The long-term adverse effects of strontium on bone (osteomalacia, pathological fractures, etc.) are unknown. Data from experimental studies and dialysis patients with renal failure raise the possibility of these adverse effects. (9) In practice, there are too many unknowns surrounding the potential risks of strontium while there is not enough evidence of clinical advantages over diphosphonates.