Strontium ranelate treatment increases osteoprotegerin serum levels in postmenopausal osteoporotic women

in BONE (2012), 50

Strontium ranelate uncouples bone formation from bone resorption in male osteoporotic patients

in Osteoporosis International (2012, March), 23(S2), 365-366

Strontium ranelate: a look back at its use for osteoporosis

in Expert Opinion on Pharmacotherapy (2010), 11(17), 2915-2927

Importance of the field: Osteoporosis is now considered as a major health problem in all developed and in most developing (non-African) coutries. Areas covered in this review: In the present review, we ... [more ▼]

Importance of the field: Osteoporosis is now considered as a major health problem in all developed and in most developing (non-African) coutries. Areas covered in this review: In the present review, we provide an extensive literature survey (MEDLINE, PubMed, Cochrane Controlled Register), for articles dealing with osteoporosis management and/or strontium ranelate, from 1920 to 2010. What the reader will gain: The objective is to provide an extensive, unbiased assessment of the available data allowing to place strontium ranelate in perspective, with other anti-osteoporosis treatments. Take home message: Owing to a positive benefit/risk ratio, strontium ranelate may now be considered as a first-line treatment in the management of osteoporosis. [less ▲]

Strontium ranelate: A new paradigm in the treatment of osteoporosis

in Drugs of Today (2003), 39(2), 89-101

Not one of the currently available medications has, so far, unequivocally demonstrated its ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once osteoporosis ... [more ▼]

Not one of the currently available medications has, so far, unequivocally demonstrated its ability to fully prevent the occurrence of new vertebral or peripheral osteoporotic fractures once osteoporosis is established. Therefore, several new therapies are currently under development to optimize the risk/benefit ratio of osteoporosis treatment. Strontium ranelate is composed of an organic moiety (ranelic acid) and of two atoms of stable nonradioactive strontium. In vitro, strontium ranelate increases Collagen and noncollagenic proteins synthesis by mature osteoblast enriched cells. The effects of strontium ranelate on bone formation were confirmed as strontium ranelate enhanced pre-osteoblastic cell replication. The stimulation by strontium ranelate of the replication of osteoprogenitor cell and collagen, as well as noncollagenic protein synthesis in osteoblasts, provides substantial evidence to categorize strontium ranelate as a bone-forming agent. In the isolated rat osteoclast assay, a pre-incubation of bone slices with strontium ranelate induced a dose-dependent inhibition of the bone resorbing activity of treated rat osteoclast. Strontium ranelate also dose-dependently inhibited, in a chicken bone marrow culture, the expression of both carbonic anhydrase 11 and the (x-subunit of the vitronectin receptor. These effects showing that strontium ranelate significantly affects bone resorption due to a direct and/or matrix-mediated inhibition of osteoclast activity and also inhibits osteoclasts differentiation, are compatible with the profile of an anti-resorptive drug. In normal rats, administration of strontium ranelate induces an improvement in the mechanical properties of the humerus and/or the lumbar vertebra associated with a commensurate increase in bone dimension, shaft and volume. Strontium ranelate was administered in 160 early postmenopausal women, in a 24-month, double-blind, placebo-controlled, prospective randomized study. Daily oral dose of 125 mg, 500 mg and 1 g of strontium ranelate were compared with a placebo. At the conclusion of the study, the percent variation of lumbar-adjusted bone mineral density from baseline was significantly different in the group receiving 1 g/day of strontium ranelate compared with placebo (+1.41% vs. -0.98%, respectively). Increase in total hip and neck bone mineral density averages, respectively, 3.2% and 2.5%. Strontium ranelate does not induce any significant adverse reaction compared with those observed in women receiving a placebo for the same duration. In a phase 11 study, the effect of strontium ranelate in postmenopausal women with vertebral osteoporotic fractures was assessed during a double-blind, placebo-controlled trial. Doses of 500 mg, 1 g and 2 g daily of strontium ranelate or placebo were given to 353 Caucasian women with prevalent osteoporosis. At the conclusion of this 2-year study, the annual increase in lumbar-adjusted bone mineral density of the group receiving 2 g of strontium ranelate was +2.97%. This result was significantly different compared with placebo. A significant increase in bone alkaline phosphatase and, over a 6-month period, a significant decrease in urinary-pyridium crosslinks (NTX) were evidenced. During the second year of treatment, the dose of 2 g was associated with a 44% reduction in the number of patients experiencing a new vertebral deformity. Bone histomorphometry showed no mineralization defects. The same percentage of withdrawals following an adverse effect was observed for patients receiving placebo and for those receiving 2 g of strontium ranelate. The compound was further investigated in a large phase III program that included two extensive trials for the treatment of severe osteoporosis, one assessing the effects of strontium ranelate on the risk of vertebral fractures (SOTI) and one evaluating its effects on peripheral (nonspinal) fractures (TROPOS). The primary analysis of the SOTI study, evaluating the effect of 2 g of strontium ranelate on vertebral fracture rates, revealed a 41% reduction in the relative risk of experiencing a first new vertebral fracture with strontium ranelate, throughout the 3-year study, compared with placebo. The TROPOS study, showed a significant (p = 0.05) reduction in the relative risk of experiencing a first non-vertebral fracture in the group treated with strontium ranelate throughout the 3-year study compared with placebo in the intention-to-treat population. A 41% reduction in the relative risk of experiencing a hip fracture was demonstrated in the per protocol population. All these results imply that strontium ranelate is a new, effective and safe treatment for vertebral and nonvertebral osteoporosis, with a unique mode of action. (C) 2003 Prous Science. All rights reserved. [less ▲]

Strontium Ranelate: A New Treatment for Postmenopausal Osteoporosis with a Dual Mode of Action

in Current Osteoporosis Reports (2005), 3(1), 30-4

In vitro, strontium ranelate increases collagen and noncollagen protein synthesis by mature osteoblast-enriched cells. Its effects on bone formation were confirmed as the drug enhanced preosteoblastic ... [more ▼]

In vitro, strontium ranelate increases collagen and noncollagen protein synthesis by mature osteoblast-enriched cells. Its effects on bone formation were confirmed as the drug enhanced preosteoblastic cell replication. In the isolated osteoclast, preincubation of bone slices with strontium ranelate-induced dose-dependent inhibition of the bone-resorbing activity of treated rat osteoclast. Strontium ranelate dose-dependently inhibited preosteoclast differentiation. Its effect in postmenopausal women with established osteoporosis was assessed during an international, prospective, double-blind, randomized, placebo-controlled phase 3 program comparing strontium ranelate 2 g daily with placebo. The 3-year analysis of the phase 3 study, Spinal Osteoporosis Therapeutic Intervention, evaluating the effect of strontium ranelate 2 g/day on vertebral fracture rates, revealed a significant 41% reduction in the relative risk of patients experiencing new vertebral fracture with strontium ranelate over 3 years. A second phase 3 study showed a significant reduction in the relative risk of experiencing a nonvertebral fracture in the group treated with strontium ranelate over 3 years. These results show that strontium ranelate is a new, effective, and safe treatment for vertebral and hip osteoporosis, with a unique mode of action, increasing bone formation and decreasing bone resorption leading to a rebalance of bone turnover in favor of bone formation. [less ▲]

Strontium ranelate: an anti-osteoporotic treatment demonstrated vertebral and nonvertebral anti fracture efficacy over 5 years in post menopausal osteoporotic women

in Osteoporosis International (2006, June), 17(Suppl.2), 14

Strontium ranelate: Dose-dependent effects in established postmenopausal vertebral osteoporosis - A 2-year randomized placebo controlled trial

in Journal of Clinical Endocrinology and Metabolism (2002), 87(5), 2060-2066

The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal ... [more ▼]

The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures. [less ▲]

Strontium ranelate: new data on fracture prevention and mechanisms of action.

in Current Osteoporosis Reports (2009), 7(3), 96-102

Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile that optimizes therapeutic adherence ... [more ▼]

Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile that optimizes therapeutic adherence. Strontium ranelate is the first compound to simultaneously decrease bone resorption and stimulate bone formation. Its anti-fracture efficacy at various skeletal sites has been established for as long as 5 years through studies of the highest methodological standards. Increases in bone mineral density observed after 1 year of treatment are predictive of the long-term fracture efficacy, suggesting for the first time in osteoporosis that bone densitometry can be used as a monitoring tool. Due to a positive risk/benefit ratio, strontium ranelate is now considered as a first-line treatment in the management of osteoporosis. [less ▲]

Strontium ranelate: The first agent of a new therapeutic class in osteoporosis.

in Advances in Therapy (2008), 25(12), 1235-56

Strontium ranelate is a new agent developed for the management of post-menopausal osteoporosis. It has a unique mode of action, based on an uncoupling between bone formation (increased) and bone ... [more ▼]

Strontium ranelate is a new agent developed for the management of post-menopausal osteoporosis. It has a unique mode of action, based on an uncoupling between bone formation (increased) and bone resorption (decreased). To review its effectiveness we searched the MEDLINE database from 1985 to 2008, as well as databases such as the Cochrane controlled register, for citations or relevant articles. After this extensive search of the literature, a critical appraisal of the data was obtained through a consensus meeting (AN, MH, SS, OB, and J-YR). We found that strontium ranelate reduces vertebral, nonvertebral, major nonvertebral, and hip fractures over 1, 3, 4, and 5 years. Its spectrum of activity covers women with osteopenia, osteoporosis, and severe osteoporosis. Elderly subjects also show a reduction in vertebral and nonvertebral fractures. Bone mineral density may be used as a monitoring tool for strontium ranelate, since early changes are predictive of long-term fracture reduction. Biochemical markers of bone turnover reflect the uncoupling between resorption and formation. The safety profile of strontium ranelate compares favorably with the other currently marketed antiosteoporosis medications. Preliminary results suggest that strontium ranelate is able to reduce the progression of spine osteoarthritis. In conclusion, strontium ranelate has the potential to be a candidate for first-line treatment of osteopenia and osteoporosis. However, further research is needed before suggesting its widespread use in osteoarthritis. [less ▲]

The strontium salt S-12911 : a new candidate for the treatment of osteoporosis

in Osteoporosis International (1996), 6(S1), 241