background Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. methods To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. results New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. conclusions Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.

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The Effects of Strontium Ranelate on the Risk of Vertebral Fracture in Women with Postmenopausal Osteoporosis

Guidelines for Canadian Drinking Water Quality

The processes of bone resorption and formation are tightly governed by a variety of systemic and local regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium (Sr), have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, strontium was found to have anabolic activity in bone, and this may have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium has been thought to have potential interest in the treatment of osteoporosis. This review summarizes the mechanisms of action of strontium on bone cells, the evidence for its beneficial effects on bone mass in vivo, and its potential therapeutic effects in osteopenic disorders.

Mechanisms of action and therapeutic potential of strontium in bone

Incorporation and distribution of strontium in bone.

The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro.

The effects of low doses of oral stable strontium (0.19-0.40% of strontium chloride) on mineral and bone metabolism were examined in normal rats using biochemical and histomorphometrical methods. The strontium levels in serum and bone rose according to the intake of the element. Oral strontium supplementation did not produce deleterious effects on body growth or on mineral homeostasis except a transitory slight decrease in serum calcium. At the dosage level of 0.40% however, strontium induced a slight defective bone mineralization. At lower levels, treated rats showed stimulated bone formation evidenced by increased amount of osteoid and increased extent of tetracycline double-labelled surface while the mineralization lag time remained normal. The osteoclastic surface and the number of acid phosphatase-stained chondroclasts and osteoclasts remained unchanged. Stimulation of bone formation without apparent change in bone resorption resulted in a 10% increase in the trabecular calcified bone volume. The strontium-induced increased osteogenesis was not associated with changes in circulating levels of 1,25(OH)2 vitamin D or in parathyroid hormone effects. The results show that small doses of oral strontium may stimulate bone formation without altering bone resorption in the rat.

http://www.promann-hamburg.de/Texte/Strontium/Strontium-Knochen-Marie-1985bisheute.pdf

Effect of low doses of stable strontium on bone metabolism in rats.

The effects of stable strontium (Sr) on bone and mineral metabolism have been studied for many years.However, most investigations were concerned with high dosage levels of Sr and the influence of low doses of Sr on bone are yet to be determined. It is known that high doses of Sr diminish the intestinal absorption of calcium (Ca) and inhibit the renal conversion of 25 hydroxyvitamin D (25-OH D) to 1,25 dihydroxyvitamin D (1,25 (OH) 2 D (Co 70, Om 72). Dietary Sr supplementation at the dose of 1.5 % in the rat induces hypocalcemia (St 62) as well as defective bone mineralization which occurs in spite of adequate amounts of Ca in the diet (St 62). By contrast, low doses of Sr do not seem to generate detectable abnormalities in mineral and bone metabolism in the rat despite significant elevation of Sr levels in serum (Sk 81). Interestingly, Sr supplementation at low dosage was reported to increase bone calcification in osteoporotic patients (Sh 52, Ja 59) but it is not known whether this beneficial effect resulted from decreased bone resorption and/ or increased bone formation. This study was therefore undertaken to evaluate the effects of low doses of stable Sr on mineral homeostasis, vitamin D metabolism and bone histology in the rat.

L. Miravet

Papers

Effect of low doses of stable strontium on bone metabolism in rats.

Effect of Stable Strontium on Bone Metabolism in Rats