Strontium is an alkaline earth metal that is chemically similar to calcium, and it has been shown in multiple large RCTs to reduce the fracture risk in postmenopausal women with osteoporosis — by a dual mechanism that combines the stimulation of the bone formation (by activating the osteoblasts and by promoting the synthesis of the collagen and of the non-collagenous bone matrix proteins) and the inhibition of the bone resorption (by inhibiting the osteoclast differentiation and activity). Strontium ranelate (the salt of strontium with the ranelic acid, which is the form used in the clinical trials) is one of the few pharmacological treatments for osteoporosis that has a dual mechanism of action, and it is approved in Europe and in many other countries for the treatment of the postmenopausal osteoporosis. The strontium is present in the body in trace amounts (approximately 0.1-0.3g total body content, with the highest concentrations in the bone, the teeth, and the aorta), and it is obtained from the diet (particularly from the seafood, the whole grains, and the drinking water) at typical intakes of 1-3mg daily — but the therapeutic dose of strontium ranelate is 2g daily, which is approximately 680mg of elemental strontium — far above the dietary intake and requiring the pharmaceutical preparation for the therapeutic effect. The strontium deficiency (as a distinct clinical entity) has not been described, because the dietary strontium intake is generally adequate for the physiological functions of strontium and because the therapeutic use of strontium requires doses that are orders of magnitude above the dietary intake. However, the low dietary strontium intake (which is common in people who do not eat seafood, whole grains, or drink mineral water) may be a risk factor for the reduced bone mineral density and for the osteoporosis, particularly when combined with the inadequate calcium and vitamin D intake.
Strontium and the Osteoblast Function
Strontium stimulates the bone formation by activating the osteoblasts and by promoting the synthesis of the collagen and of the non-collagenous bone matrix proteins — including the osteocalcin, the bone sialoprotein, and the alkaline phosphatase. The mechanism by which strontium activates the osteoblasts involves the activation of the calcium-sensing receptor (CaSR) on the osteoblast surface — strontium is an agonist of the CaSR (though with a lower potency than calcium), and the activation of the CaSR triggers the intracellular signalling cascades (including the MAPK pathway and the PI3K-Akt pathway) that promote the osteoblast differentiation, the osteoblast proliferation, and the bone matrix synthesis. This strontium-induced stimulation of the osteoblast function is one of the primary mechanisms of the increase in the bone formation markers (including the bone-specific alkaline phosphatase and the osteocalcin) that is observed in patients treated with strontium ranelate, and it explains why strontium ranelate produces a net increase in the bone formation despite also inhibiting the bone resorption.
The clinical importance of the strontium for the bone health is underscored by the observation that the strontium ranelate treatment reduces the vertebral fracture risk by 40-50% and the non-vertebral fracture risk by 15-20% in postmenopausal women with the osteoporosis. The TROPOS trial (Treatment of Peripheral Osteoporosis Study) and the SOTI trial (Spinal Osteoporosis Therapeutic Intervention) — the two large pivotal RCTs that established the efficacy of strontium ranelate for the osteoporosis — demonstrated that the strontium ranelate treatment (at 2g daily) for 3-5 years significantly reduced the risk of the vertebral fractures (by 40% in SOTI, by 39% in TROPOS) and of the non-vertebral fractures (by 16% in TROPOS) compared to placebo, with a favourable safety profile. These findings established the strontium ranelate as one of the most effective treatments for the postmenopausal osteoporosis, alongside the bisphosphonates, the denosumab, and the parathyroid hormone analogues.
Practical Application
For general strontium supplementation for the bone health, the evidence-based approach is to supplement with 1-2g of strontium ranelate daily (which provides approximately 340-680mg of elemental strontium) — but the strontium ranelate is available only by prescription in many countries and should be used under the supervision of a healthcare professional. The strontium should be taken at bedtime, at least 2 hours after the calcium-containing foods and supplements, because the calcium competes with the strontium for the absorption in the gut. For comprehensive bone support, strontium pairs well with the calcium (which is the primary mineral component of the bone — the combination of strontium and calcium is more effective than either alone for the bone health, because strontium and calcium have complementary effects on the bone remodelling), with the vitamin D (which promotes the calcium absorption and the bone mineralisation), with the vitamin K (which activates the osteocalcin and the matrix Gla protein, the two proteins that are essential for the bone mineralisation), with the magnesium (which is a cofactor for many of the enzymes of the bone matrix synthesis and which has complementary effects on the bone health), and with the silicon (which is required for the collagen cross-linking and for the glycosaminoglycan synthesis in the bone matrix).
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