Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Reginster, Jean‐Yves; Seeman, Ego; Vernejoul, M. C. De; Adami, Silvano; Compston, Juliet; Phenekos, C.; Devogelaer, J.-P.; Curiel, Manuel Dı́az; Sawicki, Andrzej; Goemaere, Stefan; Sørensen, Ole; Felsenberg, Dieter; Meunier, Pierre J.

doi:10.1210/jc.2004-1774

Cited by 939 publications

(457 citation statements)

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“…Interestingly, strontium ranelate, an approved antiosteoporotic drug, (27)(28)(29) was found to activate the CaSR in osteoblasts (30), resulting in activation of osteoblastic cell replication, differentiation, and survival (31,32). In OVX rats, strontium ranelate-treated animals exhibited increased bone formation and decreased bone resorption, resulting in prevention of trabecular bone loss, improved bone microarchitecture, and strength (33,34).…”

Section: Present Anabolic Therapiesmentioning

confidence: 99%

“…In OVX rats, strontium ranelate-treated animals exhibited increased bone formation and decreased bone resorption, resulting in prevention of trabecular bone loss, improved bone microarchitecture, and strength (33,34). In postmenopausal osteoporotic women, strontium ranelate treatment increased bone mineral apposition rate and improved trabecular microarchitecture (35), which was associated with reduced fracture risk (27,29). Thus, specific activation of the CaSR in bone cells may be efficient to increase bone mass and strength independently of changes in PTH secretion.…”

Section: Present Anabolic Therapiesmentioning

confidence: 99%

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Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Marie¹,

Kassem²

2011

European Journal of Endocrinology

183

141

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Objective: Age-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration. Methods: A limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010. Results and discussion: We present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.

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Section: Present Anabolic Therapiesmentioning

confidence: 99%

Section: Present Anabolic Therapiesmentioning

confidence: 99%

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Marie¹,

Kassem²

2011

European Journal of Endocrinology

183

141

View full text Add to dashboard Cite

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“…We report here the results of a study that evaluated the influence of vitamin D status on strontium ranelate absorption in postmenopausal women, the target population of this medication (2,3). Postmenopausal women are also at risk for vitamin D deficiency because older individuals spend less time in the sun and older skin has significantly less capacity to synthesize vitamin D from sunlight than the skin of younger people (18,23).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the aim of treatment is the prevention offractures (1). Strontium ranelate is currently approved for osteoporosis treatment with significant anti-fracture efficacy (2,3).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D supplementation and strontium ranelate absorption in postmenopausal women with low bone mass

Vilaça

Camargo

Rocha

et al. 2014

European Journal of Endocrinology

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Background: Strontium ranelate is used to treat osteoporosis. Calcium (Ca) and strontium (Sr) have common chemical features and are absorbed by the same pathways. Vitamin D has a main role in calcium intestinal absorption. The aim of this study was to investigate whether vitamin D status is a determinant of strontium ranelate absorption. Methods: Twenty-five patients with vitamin D deficiency (25(OH)D!50 nmol/l) and 25 with vitamin D sufficiency (25(OH)DO75 nmol/l) underwent a 4-h oral Sr overload test. Sr absorption was evaluated as the fraction of absorbed dose and the area under the curve. After the baseline overload test, the deficient patients were treated until reaching sufficient vitamin D levels (25(OH)DO75 nmol/l) and the test was repeated. Results: Changing vitamin D status from deficient to sufficient resulted in a significant increase in 1,25(OH) 2 D (24.97G 4.64!34.62G9.14 pg/ml, P!0.001) and a reduction in parathyroid hormone (73.87G37.50!58.24G20.13 pg/ml, PZ0.006). Nevertheless, no differences were found in the parameters used to evaluate Sr absorption between the vitamin D deficient and sufficient groups. In addition, vitamin D3 replacement in the deficient group did not result in enhanced Sr absorption. Conclusion: Vitamin D status did not interfere with strontium ranelate absorption. Taking into account the benefits of adequate vitamin D status in osteoporotic patients, we strongly recommend the treatment of vitamin D deficiency. However, the data demonstrate that such treatment does not enhance strontium ranelate absorption in patients with mild deficiency.

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“…Strontium ion's mechanism of action is not fully understood, but it is thought to upregulate differentiation of osteoprogenitors or to directly stimulate bone formation. [52,53] Autefage et al designed experiments that exposed MSCs to various levels of strontium ion and measured changes in gene expression over time. We analysed the microarray data using the sparse Bayesian feature selection methods to identify genes of highest relevance to the strontium-induced bone formation.…”

Section: Discovery Of Novel Biomarkers and Mechanisms Of Action By Spmentioning

confidence: 99%

Adrien Albert Award: How to Mine Chemistry Space for New Drugs and Biomedical Therapies

Winkler

2015

Aust. J. Chem.

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It is clear that the sizes of chemical, 'drug-like', and materials spaces are enormous. If scientists working in established therapeutic, and newly established regenerative medicine fields are to discover better molecules or materials, they must find better ways of probing these enormous spaces. There are essentially five ways that this can be achieved: combinatorial and high throughput synthesis and screening approaches; fragment-based methods; de novo molecular design, design of experiments, diversity libraries; supramolecular approaches; evolutionary approaches. These methods either synthesise materials and screen them more quickly, or constrain chemical spaces using biology or other types of 'fitness functions'. High throughput experimental approaches cannot explore more than a minute part of chemical space. We are nevertheless entering into an era that is data dominated. High throughput experiments, robotics, automated crystallographic beam lines, combinatorial and flow synthesis, high content screening, and the 'omics' technologies are providing a flood of data, and efficient methods for extracting meaning from it are essential. This paper describes how new developments in mathematics have provided excellent, robust computational modelling tools for exploring large chemical spaces, for extracting meaning from large datasets, for designing new bioactive agents and materials, and for making truly predictive, quantitative models of the properties of molecules and materials for use in therapeutic and regenerative medicine. We describe these broadly applicable modelling tools and provide examples of their application to serum free stem cell culture, pathogen resistant polymers for implantable devices, new markers and biological mechanisms derived from mathematical analyses of gene array data, and pharmacokinetically important physicochemical properties of small molecules. We also discuss biologically conserved peptide motifs as a design framework for small molecule drugs and give examples of the application of this concept to drug design.

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Strontium Ranelate Reduces the Risk of Nonvertebral Fractures in Postmenopausal Women with Osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study

Cited by 939 publications

References 20 publications

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Vitamin D supplementation and strontium ranelate absorption in postmenopausal women with low bone mass

Adrien Albert Award: How to Mine Chemistry Space for New Drugs and Biomedical Therapies

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