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

Stroop interference and negative priming in normal aging

Poster (2004, December 02)

Structural analysis of rodent growth hormone genes: application to genetic forms of hypopituitarism

in Endocrinology (1982), 110(5), 1672-1675

Analysis of GH gene structure in the mouse permits evolutionary comparisons with GH gene structure in the rat and provides information about the mechanism responsible for heritable deficiencies of ... [more ▼]

Analysis of GH gene structure in the mouse permits evolutionary comparisons with GH gene structure in the rat and provides information about the mechanism responsible for heritable deficiencies of anterior pituitary hormones. The little mutation in mice is analogous to autosomal recessive, isolated, partial deficiency of GH in man, whereas the Snell dwarf mutation is a model for autosomal recessive deficiency of GH, TSH, and PRL. Mouse cellular DNA was digested with the restriction enzymes Eco RI, Bam HI, Bgl II, Hind III, and Kpn I, singly and in combination. Gene sequences containing coding information for GH were detected by hybridization to a radiolabeled recombinant DNA probe complementary to a rat GH mRNA. The results of genomic restriction analysis indicate that there is a single type of mouse GH gene sequence per haploid genome with a length equal to or less than 32000 base pairs. The distances separating 6-base restriction sites close to the mouse GH gene differ from those close to the rat GH gene. A Kpn I site in the codons for amino acids 103 and 104 of rat GH is absent in the mouse gene. Restriction patterns of DNA from little and Snell dwarf mice did not differ from those of normal mice, indicating that these mutations do not involve deletions of the mouse GH gene. [less ▲]

Structural and core parameters of the hot B subdwarf KPD 0629-0016 from CoRoT g-mode asteroseismology

in Astronomy and Astrophysics (2010), 524

Context. The asteroseismic exploitation of long period, g-mode hot B subdwarf pulsators (sdBVs), undermined so far by limitations associated with ground-based observations, has now become possible, thanks ... [more ▼]

Context. The asteroseismic exploitation of long period, g-mode hot B subdwarf pulsators (sdBVs), undermined so far by limitations associated with ground-based observations, has now become possible, thanks to high quality data obtained from space such as those recently gathered with the CoRoT (COnvection, ROtation, and planetary Transits) satellite. Aims. We propose a detailed seismic analysis of the sdBVs star KPD 0629-0016, the first compact pulsator monitored with CoRoT, using the g-mode pulsations recently uncovered by that space-borne observatory during short run SRa03. Methods. We use a forward modeling approach on the basis of our latest sdB models, which are now suitable for the accurate com- putation of the g-mode pulsation properties. The simultaneous match of the independent periods observed in KPD 0629-0016 with those of the models leads objectively to the identification of the pulsation modes and, more importantly, to the determination of the structural and core parameters of the star. Results. The optimal model we found closely reproduces the 18 observed periods retained in our analysis at a 0.23% level on av- erage. These are identified as low-degree (l = 1 and 2), intermediate-order (k = −9 through −74) g-modes. The structural and core parameters for KPD 0629-0016 are the following (formal fitting errors only): Teff = 26 290 ± 530 K, log g = 5.450 ± 0.034, M∗ = 0.471 ± 0.002 M⊙, log (Menv/M∗) = −2.42 ± 0.07, log (1 − Mcore/M∗) = −0.27 ± 0.01, and Xcore(C+O) = 0.41 ± 0.01. We addition- ally derive an age of 42.6 ± 1.0 Myr after the zero-age extreme horizontal branch, the radius R = 0.214 ± 0.009 R⊙, the luminosity L = 19.7 ± 3.2 L⊙, the absolute magnitude MV = 4.23 ± 0.13, the reddening index E(B − V) = 0.128 ± 0.023, and the distance d = 1190 ± 115 pc. Conclusions. The advent of high-precision time-series photometry from space with instruments like CoRoT now allows as demon- strated with KPD 0629-0016 the full exploitation of g-modes as deep probes of the internal structure of these stars, in particular for determining the mass of the convective core and its chemical composition. [less ▲]

Structural and ecofunctional biodiversity of the amphipod crustacean benthic taxocoenoses in the Southern Ocean

in Belgian Scientific Research Programme on the Antarctic-Phase 4. Vol 1. Marine Biota and Global Change (2003)