Strontium Bone Maker - Make Stronger Bones
|Strontium Bone Maker 60 VC - Strengthen Bones||Darrell Miller||07/27/05|
July 27, 2005 12:06 PM
Author: Darrell Miller (firstname.lastname@example.org)
Subject: Strontium Bone Maker 60 VC - Strengthen Bones
Helps maintain strong, healthy bones.*
In Vitro and Animal Studies
Strontium is a bone-seeking mineral incorporated by ionic substitution for calcium onto the crystal surface of bone.2 In the test-tube (in vitro), strontium inhibits the activity of osteoclasts, bone cells that break down bone, or “resorb” bone as part of the normal bone remodeling process.3 The effect of strontium, in the form of strontium ranelate (a salt of strontium and ranelic acid), was studied in monkeys over a six-month period. Strontium altered the remodeling of bone in the monkeys, resulting in decreased bone resorption with a concomitant maintenance of bone formation. A trend toward increased volume of osteoid, the organic matrix of bone, was observed, although this was not associated with defects in bone mineralization.4 In another animal study, monkeys fed strontium at high doses for six weeks showed a marked increase in bone strontium content. No harmful effects on bone mineral chemistry or structure occurred.5 At low doses, strontium has been shown to increase the number of bone forming sites in thighbones of adult rats, without adverse effects on the mineral content of bone or mineralization of the organic bone matrix.6 Strontium was shown to reverse bone loss induced by estrogen deficiency in rats.7
Human clinical trials have examined the effect of strontium on bone in postmenopausal women. In the dose-ranging (Phase 2) PREVOS trial, women in early menopause were administered strontium ranelate or a placebo for two years. Strontium ranelate was given at daily doses of 125 mg, 500 mg or 1 gram. (Total weight of compound; strontium plus ranelic acid). Compared to women in the placebo group, who lost bone, women on strontium at the 1 gram dose showed statistically significant increases in bone mineral density (BMD) of the hip, thigh and lumbar spine. Biochemical markers of bone formation, such as serum alkaline phosphatase, increased. No effect on markers of bone resorption was observed, leading to the conclusion that strontium ranelate, at the 1 gram daily dose, increased bone formation without decreasing bone resorption proportionally. It was concluded that 1 gram per day is the minimum effective daily dose of strontium ranelate in these women.8
In another Phase 2 trial (STRATOS trial), 353 postmenopausal women with osteoporosis, who had experienced at least one spinal fracture, took strontium ranelate for two years at daily doses of 500 mg, 1 gram or 2 grams. Women on the 2-gram dose showed a significantly greater increase in lumbar spine BMD than those on placebo. The number of subjects who had new spinal deformities was significantly reduced.9 As in the PREVOS trial, serum levels of alkaline phosphatase, a marker of bone formation, increased, while markers of bone resorption (breakdown) decreased. The overall conclusion is that the minimum effective daily dose of strontium ranelate (whole compound) is 1 gram in early postmenopausal non-osteoporotic women and 2 grams in postmenopausal women with osteoporosis.10
Phase 3 efficacy studies on strontium ranelate have been conducted on 1649 subjects in 12 countries. These studies began with an open-run (non-controlled study period in which subjects took calcium and vitamin D supplements to normalize their blood levels of these nutrients.11 Following this, two parallel groups were administered 2 grams daily of strontium ranelate or placebo for 3-years. The subjects continued to take calcium and vitamin D during the study. In subjects on strontium ranelate, BMD increased in the lumbar vertebrae by 14.4 percent and in the thighbone by 8.3 percent. The number and risk of vertebral fractures decreased.12
Suggested Use: Take two capsules daily. Calcium intake must also be adequate. Do not take this product with calcium supplements.
Strontium ranelate was well-tolerated in the trials discussed above. The incidence of adverse events in subjects on strontium ranelate was statistically equivalent to the placebo groups, and no negative effects on hematology and other biochemical parameters have been observed.
In view of the fact that subjects on the strontium trials also took calcium, and in some cases vitamin D, to maintain normal blood levels of these nutrients, it is important to ensure calcium and vitamin D intakes are adequate when supplementing with strontium. This is underscored by earlier research on animals suggesting that increasing the intake of strontium via diet may demineralize bone when calcium is deficient.13 In rats with chronic kidney failure, strontium has been shown to cause osteomalacia, a condition in which bone is softened due to lack of mineral content. For this reason, people on kidney dialysis should not use strontium supplements.14
1. Shorr E, Carter AC. The usefulness of strontium as an adjuvant to calcium in the remineralization of the skeleton in man. Bull Hosp Joint Dis 1952; 13:59 -66.
2. Dahl SG, Allain P, Marie PJ, et al. Incorporation and distribution of strontium in bone. Bone 2001;28(4):446-53.
3. Baron R, Tsouderos Y. In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 2002; 450:11-17.
4. Buehler J, Chappuis P, Saffar JL, et al. Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis) Bone 2001;29(2):176-79.
5. Boivin G, Deloffre P, Perrat B, et al. Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res. 1996 Sep;11(9):1302-11.
6. Grynpas MD, Hamilton E, Cheung R, et al. Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect. Bone 1996;18(3):253-9.
7. Marie PJ, Hott M, Modrowski D, et al. An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 1993;8(5):607-15.
8. Reginster JY, Deroisy R, Dougados M, et al. Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose ranging, placebo-controlled PREVOS trial. Osteoporosis Int 2002; 13:925-31.
9. Meunier PJ, Slosman DO, Delmas PD, et al. Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis––a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 2002;87(5):2060-66.
10. Reginster JY, Meunier PJ. Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies. Osteoporosis Int 2003; 14(Suppl 3):S56-S65.
11. Meunier PJ, Reginster JY. Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the treatment of women with postmenopausal osteoporosis. Osteoporosis Int 2003;14(Suppl 3):S66-76.
12. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350(5):459-68. 13. Grynpas MD, Marie PJ. Effects of strontium on bone quality and quantity in rats. Bone 1990;11:313-19.
14. Schrooten, I, Cabrera W, Goodman WG, et al. Strontium causes osteomalacia in chronic renal failure in rats. Kidney Int 1998;54:448-56.
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