Strontium Bone Maker
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
strontiumcitrate (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
Clinical Trials
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 strontiumcitrate or a placebo for two years.
Strontium citrate 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 citrate, 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 strontiumcitrate 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 strontiumcitrate 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 strontiumcitrate (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 strontiumcitrate
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
strontiumcitrate or placebo for 3-years. The subjects continued
to take calcium and vitamin D during the study. In subjects on
strontium citrate, 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
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
- 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.
- Dahl SG, Allain P, Marie PJ, et al. Incorporation and distribution of
strontium in bone. Bone 2001;28(4):446-53.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Reginster JY, Meunier PJ. Strontium ranelate phase 2 dose-ranging studies:
PREVOS and STRATOS studies. Osteoporosis Int 2003; 14(Suppl 3):S56-S65.
- 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.
- 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.
- Grynpas MD, Marie PJ. Effects of strontium on bone quality and quantity in
rats. Bone 1990;11:313-19.
- 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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