Strontium for osteoporosis: to dose or to megadose?

Townsend Letter for Doctors and Patients, May, 2006 by Alan R. Gaby

Studies published over the past several years have shown that supplementation with pharmacological doses of strontium (as strontium ranelate) can increase bone mineral density (BMD) and reduce fracture risk in postmenopausal women. The amount of strontium used in the largest of these studies was 680 mg per day, which is roughly 200 to 600 times the amount found in a typical diet (1 to 3 mg per day). Based on this research, high-dose strontium therapy has become popular among practitioners of natural medicine as a treatment for osteoporosis.

While no serious side effects were reported in studies lasting up to three years, questions remain about the long-term safety of high-dose strontium. It is also not clear whether pharmacological doses are necessary to prevent and treat osteoporosis successfully. According to one study, 170 mg of strontium per day was more effective than 680 mg per day for reducing fracture risk, which raises the possibility that even lower doses might be as effective as, or more effective than, the doses that have been studied.

Strontium and Bone

Strontium is a trace mineral that is chemically similar to calcium. Ingested strontium from the diet and drinking water is deposited in bone, where it replaces a small amount of calcium in hydroxyapatite crystals and remains in the skeleton for years or decades. In animal studies, strontium supplementation increased bone formation and inhibited bone resorption, actions that would be expected to have a favorable effect on BMD.

In the largest published clinical trial, 1,649 postmenopausal women with osteoporosis received 680 mg per day of strontium or placebo for three years. (1) The mean BMD of the lumbar spine increased progressively in the strontium group and was 8.1% higher than that in the placebo group after three years (p < 0.001). Compared with placebo, strontium reduced the incidence of vertebral fractures by 49% after one year and by 41% at three years.

Are High Doses Safe?

The beneficial effects of strontium reported in this study must be weighed against the fact that high-dose strontium (1.5% of the diet or greater) caused mineralization defects resembling rickets and inhibited the synthesis of 1,25-dihydroxyvitamin D (the active form of vitamin D) in experimental animals. (2,3) In one study, as little as 0.19% dietary strontium caused hypomineralization and reduced the size of bone mineral crystals in young rats. (4) That amount of strontium would be equivalent to 792 mg per day for a typical human diet providing 2,000 kcal per day. (5) While the significance of these changes in bone physiology is not clear, they could represent subtle manifestations of the rickets-like abnormalities that have occurred with higher strontium doses. It has been suggested that the deleterious effects on bone that resulted from strontium supplementation were due to the concomitant feeding of calcium-deficient diets. However, in the study in which 0.19% strontium caused changes in bone, the diet contained 0.5% calcium, which would be equivalent to more than 2,000 mg of calcium per day for humans. (6)

The association between strontium intake and rickets prevalence was investigated in an observational study of 1,596 Turkish children. Among 650 children living in villages in which the soil strontium concentration was greater than 350 parts per million (ppm), the prevalence of rickets was 31.5%, as compared with 19.5% in villages where the soil contained less than 350 ppm (p < 0.001). (7)

In the three-year clinical trial mentioned previously, 20 participants who had received 680 mg per day of strontium for three years consented to a bone biopsy. No evidence of osteomalacia or a mineralization defect was found. However, the investigators biopsied only mature (lamellar) bone, whereas the earliest evidence of a mineralization defect would likely be observed in newly formed bone. Of note, the extent to which strontium prevented fractures decreased as the study progressed (49% reduction after one year, 41% reduction after three years), even though BMD increased linearly with each year of strontium supplementation. One would have expected that protection against fractures would have more closely paralleled changes in BMD. While it is not possible to draw definitive conclusions from these data, they are consistent with the possibility that new bone formed under the influence of high-dose strontium therapy is not of high quality.

Strontium supplementation also increased thyroid-gland weight and decreased pituitary weight in rats, with a "no-observed-adverse-effect-level" roughly equivalent to 41 mg per day for humans. (8)

Are Low Doses Effective?

Investigators have focused on relatively high strontium doses, because they are the most effective at increasing BMD. However, in a two-year study of postmenopausal women with osteoporosis, the incidence of new vertebral fractures was lower in the group receiving 170 mg per day of strontium than in those receiving 680 mg per day (38.8% vs. 42.0%), even though BMD increased with increasing strontium doses. (9) There have been no studies in humans using less than 170 mg per day.