[Turn] strontium ranelate treatment of osteoporosis

Strontium ranelate is the original study by the French pharmaceutical company Servier original new class of anti-osteoporosis drugs, is the only drug with a dual mechanism of action, creating a new era in the treatment of osteoporosis. The one hand, , Optek the United States through the calcium sensing receptor pathway promotes bone cell replication before the differentiation of osteoblasts increased the number of new bone formation, improve bone microstructure. On the other hand, Optek United States increased the secretion of OPG and reduce RANKL expression, thereby inhibiting osteoclast differentiation before, so that the number of osteoclasts decreased production and activity decreased, thereby reducing bone resorption, bone turnover restore the dynamic balance of fundamentally the treatment of osteoporosis. a controlled study of bone micro-CT imaging revealed Optek United States to promote new bone formation, and fundamentally improve osteoporosis cortical and trabecular bone microstructure. new and better bone bone, bone strength improved significantly. international multi-center clinical registration SOTI study showed that: Optek U.S. treatment for 3 years reduced the incidence of vertebral fractures 41%, spine BMD was significantly improved, and easy to take and well tolerated. TROPOS study shows that: Optek hip fracture and the United States can reduce the risk of peripheral fractures. Optek the United States has 8 years of extensive anti-fracture efficacy of evidence based medicine, is the only effective in preventing the young age of 50 to 65 and 80 osteoporosis patients over the age of fractures in osteoporosis drugs. its innovative mechanism of action, Optek the United States has been in Europe, Asia and other guidelines recommend as first-line drugs, and China, written prior to listing Jibei official "guide to diagnosis and treatment of osteoporotic fracture", published in the October 2008 "Chinese Orthopaedics "on. Optek United States also won the Frost & Sullivan Award and the 2004 Award for the best economic efficacy. Optek the United States in 2005 to obtain Prix Galien Award (prize known as the Nobel Prize in the field of pharmaceutical R & D), the participating experts Optek the advent of the United States agreed that, not only for the treatment of osteoporosis has brought new breakthroughs, but also brought new hope to patients. Manual:

【Drug name】 generic name: strontium ranelate dry suspension English name: Strontium Ranelate for Suspension (OSSEOR ?) Pinyin Name: Leinaisuansi Ganhunxuanji Trade Name: Optek the U.S. The main components major components of the chemical name: strontium ranelate, 5 - [bis (carboxymethyl ) amino] -2-- carboxyl -4-- cyano -3-- thiophene acetic acid two strontium salts. 【Molecular Formula】 C12H6N2O8S, Sr2 【Molecular Weight】 513.5 【Structural formula】 【Properties】 This product is yellow powder. pharmacological effects】 【Pharmacology and Toxicology In vitro study found that strontium ranelate increased bone tissue culture of bone formation, bone cell culture in osteoblast precursors to improve replication and collagen synthesis; by reducing osteoclast differentiation and activity to reduce the absorption of bone resorption . thus restoring the balance of bone turnover, is conducive to new bone formation. in the rat model, strontium ranelate increases trabecular bone quality, quantity and thickness; to improve bone strength. in the treatment of an animal or human bone tissue, the strontium adsorption on crystal surface, the carbon in the newly formed bone substitute lime little calcium crystals. strontium ranelate does not change the characteristics of bone crystals. In Ⅲ clinical studies, daily strontium ranelate 2 overcome by up to 60 months after iliac crest bone biopsies obtained data of strontium ranelate is not observed in bone mass and mineralization of harmful effects. the distribution of strontium in bone tissue and its (compared with calcium) to X-ray combined effect of increased absorption of lead dual-energy X-ray absorption absorptiometry (DXA) measured bone mineral density (BMD) to enlarge. The existing data suggest that the FDA 2 g / day treatment for 3 years, about 50% of the BMD measurements change is caused by these factors. Therefore, in using this treatment in the interpretation of BMD change to take into account these factors. Based on the results of clinical studies in stage Ⅲ in the treatment of this product has proven efficacy against fractures of the case before treatment after treatment compared to the determination of this product in lumbar spine BMD annual average increase of 4%, femoral neck increased by 2%; treatment for 3 years increased by 13% to 15% and 5% to 6%. In Ⅲ clinical studies, compared with placebo, after 3 months from treatment start to 3 years after treatment, biochemical markers of bone formation (bone - specific alkaline phosphatase and type Ⅰ procollagen C terminal peptide) was increased. The biochemical markers of bone resorption (serum type Ⅰ collagen cross-linked C telopeptide (CTX) or urinary crosslinked N telopeptide (NTX)) decreased. as strontium ranelate secondary pharmacological effects, found that calcium and parathyroid hormone (PTH) plasma concentrations decreased slightly, phosphorus and total alkaline phosphatase activity increased, but did not observe any clinical consequences. toxicology preclinical safety pharmacology, genotoxicity, carcinogenic potential study did not found that the goods are at special risk to humans. rodent long-term use of high dose of strontium ranelate leading to bone and teeth abnormalities, including spontaneous fractures and delayed mineralization. These effects occur, the action level of strontium in bone than When the clinical long-term medication in patients with 2 to 3 times higher, and can be reversed after treatment is stopped. in rats and rabbits, developmental toxicology studies, strontium ranelate led to progeny animal bone and teeth abnormalities (such as bending of long bones and wavy ribs). In rats, 8 weeks after discontinuation of these effects are reversed. 【Pharmacokinetics of strontium ranelate is composed of two stable strontium ranelate atom and a molecule composed of an integral part of making the molecular weight, pharmacokinetics, and drug tolerance to achieve the best compromise. strontium ranelate and pharmacokinetics in healthy young men and healthy postmenopausal women were measured, and in postmenopausal osteoporosis in women, including elderly women in long-term treatment during the process were determined. As high ranelate polarity, the absorption, distribution and plasma protein binding rate is lower. in animals and humans, no accumulation of ranelate, also found no evidence of its metabolism. ranelate absorbed quickly by the kidneys to prototype discharge. Kelei Nai strontium absorption after oral administration of 2, the absolute bioavailability of strontium is about 25% (range 19 ~ 27%). After a single oral dose of 3 to 5 hours to reach maximum plasma concentration. After 2 weeks of treatment to reach steady state. and 3 hours after meals taking strontium ranelate, compared with calcium or food while taking strontium strontium ranelate reduced the biological utilization of about 60 to 70%. because the relatively slow uptake of strontium, strontium before and after taking food and calcium should be avoided. oral vitamin D supplements had no effect on the absorption of strontium. Distribution of volume of distribution of strontium is about 1 liter / kg. strontium binding to human plasma proteins is low (25%), and with a higher affinity for bone tissue. strontium ranelate 2 g / day treatment for patients up to 60 months to determine the anterior superior iliac crest bone biopsy the concentration of strontium in bone tissue, the results show about 3 years in the treatment of bone strontium concentrations may reach a plateau. There is no data to show that after stopping treatment strontium bone removed from the dynamics. biotransformation as a divalent cation, strontium is not is metabolized. strontium ranelate does not inhibit cytochrome P450 enzymes. clear the removal of strontium has nothing to do with the time and dose, the effective half-life of approximately 60 hours, cleared by the kidneys and gastrointestinal tract, plasma clearance rate is about 12 hours (CV 22 %), renal clearance is about 7ml/min (CV 28%). In the case of special clinical pharmacokinetics of the elderly population pharmacokinetic data, in the target population in the age and apparent clearance rate of strontium and unrelated. renal dysfunction in patients with mild - moderate patients with impaired renal function (creatinine clearance rate of 30 ~ 70ml/min), with the rate of decline in creatinine clearance, thus resulting in reduced clearance of strontium (creatinine clearance rate in the range of 30 ~ 70ml/min, about 30% decrease), resulting in increased plasma concentrations of strontium. In Ⅲ clinical study, 85% of selected patients when creatinine clearance ranging between 30 ~ 70ml/min, 6% of the patients Diyu 30ml/min, and the average creatinine clearance rate is about 50ml/min. Yinci mild - moderate renal impairment Bingren not need to adjust Jiliang. no severe renal impairment Bingren TO PHARMACOKINETIC such information (creatinine clearance below 30ml/min). liver injury in patients without liver dysfunction in patients with pharmacokinetic information. Because the pharmacokinetic characteristics of strontium is expected to no effect. 【Storage】 Sealed kept below 30 ℃ . 【Indications】 treatment of postmenopausal osteoporosis to reduce vertebral and hip fracture risk. 【Packing】 paper - polyethylene - aluminum - polyethylene bags, 7,14,28 bags / box 【Validity】 36 months Zhunzi】 【[imported drugs registration No] H 20080315 (7 bags, 14 bags / box), H 20080320 (28 bags / box)