Action mechanism of strontium ranelate

Characteristics of strontium Strontium was discovered in 1790 in a mine close to the Scottish village Strontian and was isolated in 1808. Strontium is one of the alkaline earth metals and is never found in its free form in nature because it easily oxidises, forming strontium oxide. Strontium, along with calcium and magnesium belongs to group 2 of the periodic table which are divalent cations, which, in biological liquids can have different degrees of bonds with blood proteins. The binding to proteins of strontium is in the same order of magnitude as that of calcium. In the human body there are only traces of strontium. A normal diet supplies from 2 to 4 mg of strontium per day, although the quantity can be higher if the diet is rich in cereals or vegetables. Given the similarity in the behaviour of both elements, the radioisotopes of strontium have been used for kinetic studies of the metabolism of calcium. However, there are important biological differences between them, which are in part explained by the greater molecular weight of strontium. Common transportation pathways have been described, for example strontium competes with calcium in intestinal absorption and in renal tubular reabsorption. Strontium is absorbed less than calcium, this difference in the intestinal tract could be due, in part, to the smaller size of the calcium atom. On the other hand, the renal clearance of strontium is nearly three times greater than that of calcium, perhaps due to a greater secondary tubular absorption because of the larger size of the strontium atom. Relationship of strontium with bone The quantity of strontium in the skeleton is very small, and represents only 0.035% of the content of calcium. After its administration it is deposited almost exclusively in bone. Like sodium and lead, strontium can substitute for calcium in the position which it occupies in hydroxyapatite. In 1952, Shorr and Carter demonstrated that the addition of a moderate quantity of strontium lactate improves the deposition of calcium in the bone. One can say that this observation was the first suggestion in the literature that strontium could be useful in the treatment of alterations in bone metabolism. In 1959, McCaslin showed in a small study that in patients with osteoporosis strontium lactate reduced bone pain, at the same time as improving the X-ray images of demineralisation. However, these observations did not awaken great interest in the researchers of that time, probably due to the mineralisation defects which a high dose of strontium was known to produce. Subsequently, in the 90s, from the study of Marie et al., various researchers confirmed progressively and uniformly, that strontium ranelate reduced bone resorption, maintaining formation and increasing bone volume without inducing mineralisation defects.