El ranelato de estroncio en el tratamiento de la osteoporosis

Resumo

Strontium (Sr), chemical element number 38, has a content in normal diets of 0.022-0.046 mmol/day and its physiological levels are between 0.11-0.31 mmol/l. Its behaviour is similar to that of calcium. It is distributed in plasma, extracellular liquid, soft tissues and skeleton. It binds to serum proteins and is eliminated through urine and faeces. If administered alone, 25-30% is absorbed and this absorption is diminished if it is administered with calcium or food. Although absorbed both actively and passively, active absorption is vitamin-D dependent. As a divalent cation, Sr is not metabolized. In studies carried out with animals, it was shown not to have toxic effects on bone cells or on mineralization, if the doses are less than 1% of the diet (low dose ≤ 4 mmol Sr/Kg/day). A high dose of Sr induces skeletal abnormalities (rickets, mineralization defects) especially in animals with a calciumpoor diet. In studies performed, Sr inhibits bone resorption and increases the replication of pre-osteoblastic cells and secondarily the synthesis of collagen matrix. Strontium ranelate (rSr) comprises an organic part (ranelic acid) and two atoms of strontium, is absorbed orally and its absolute bioavailability is 20-25%. Sr binds little to proteins and has a great affinity for bone tissue. rSr has “in vitro” effects on bone cells, increasing DNA synthesis and the synthesis of collagen and non-collagen proteins. rSr inhibits bone resorption as it diminishes the differentiation of pre-osteoclasts and increases the replication of pre-osteoblastic cells, thus increasing bone formation. The Phase II studies with different doses of rSr versus placebo, in order to assess the dose and side effects, it can be summarized by saying that the minimum effective dose of rSr to prevent serious bone loss is 1 g/day and a dose of 2 g/day offers the best combination of efficacy. Two Phase III placebo-controlled studies conducted with 2 g/day of rSr, one into the prevention of vertebral fractures (SOTI) and the other into peripheral fractures (TROPOS), have found vertebral fractures to be reduced by 49% in the first year and by 41% after three years, with BMD increased by +6.8% and +8.1%, already adjusted, versus the baseline values and placebo, respectively. With respect to non-vertebral fractures (TROPOS) in women at high risk of fractures (women ≥ 74 years of age and femoral neck BMD of T ≤ -3), it is associated with a 36% reduction in the risk of hip fractures. The increase, compared with baseline values and placebo respectively, is +2.85% and +4.1% in femoral neck BMD and +3.58% and +4.9% in total hip, all figures also corrected. Bone alkaline phosphatase is increased and C-telopeptide diminished. Adverse events were scant and the most frequent was diarrhoea (6.1%), which disappeared after the first three months. rSr induces to the reduction in vertebral and non-vertebral fractures, is well tolerated and can be a useful therapy for the prevention of osteoporotic fractures in women with osteoporosis.