国产 89SrCl2治疗肿瘤骨转移灶所致骨痛临床多中心研究

目的　验证上海科兴药业公司提供的89SrCl2 注射液治疗转移性骨肿瘤所致骨痛的疗效。方法　试验采用随机、双盲、阳性药物 (英国Amersham公司生产的Metastron)对照 ,5个中心参加验证。对 90例原发病灶诊断明确的恶性肿瘤骨转移患者进行骨痛镇痛治疗 ,其中资料完整的Ⅰ组(验证组 ) 5 9例 ,Ⅱ组 (对照组 ) 2 9例 ,余 2例患者剔除。Ⅰ组中男 30例 ,女 2 9例 ,年龄 2 5～ 80 (5 9 95±13 80 )岁 ;原发性恶性肿瘤肺癌 2 1例 ,乳腺癌 2 4例 ,前列腺癌 12例 ,胃癌、肝癌各 1例 ;治疗前骨痛评分为 6～ 12 (7 5 9± 1 5 9)。Ⅱ组中男 11例 ,女 18例 ,年龄 35～ 91(5 8 93± 14 6 0 )岁 ;原发性恶性肿瘤肺癌 10例 ,乳腺癌 12例 ,前列腺癌 6例 ,胃癌 1例 ;治疗前骨痛评分为 6～ 9(7 14± 1 4 6 )。入选患者均以 14 8MBq静脉注射给药 ,疼痛得分大于 6 ,体力状况评分平均≤ 70分 ,患者预期生存期至少大于3个月。全身99Tcm 亚甲基二膦酸盐 (MDP)骨显像示多发骨骼放射性浓聚灶 ,并经实验室及其他影像学检查证实。治疗后观察 3个月。结果　Ⅰ组镇痛有效率为 6 2 71% (37 5 9例 ) ;其中无效占 15 2 4 %(9 5 9例 ) ,好转占 2 2 0 3% (13 5 9例 ) ,显效占 5 5 93% (33 5 9例 ) ,完全缓解占 6 78% (4 5 9例 )。Ⅱ组镇     

生物活性锶羟基磷灰石骨水泥应用于椎体后凸成形术的生物力学研究

目的探讨单侧和双侧球囊扩张注射生物活性锶羟基磷灰石骨水泥（SrHAC）行椎体后凸成形术对骨折椎体模型的高度和生物力学性能的修复能力。方法从2具新鲜冰冻人脊柱标本中分离14个椎体（T8～L5），随机分为单侧组（单侧球囊扩张注射SrHAC）和双侧组（双侧球囊扩张注射SrHAC），每组7个椎体。测量各椎体的骨密度、原始高度后，对各椎体标本施加轴向压力负载，测出各椎体的原始强度和原始刚度，并建立椎体压缩骨折模型。测量椎体骨折后的刚度。在c型臂x线机下手术，术中控制球囊扩张的体积均为3．00mL，术后测量各椎体的高度、强度和刚度。用单因素方差分析比较两组椎体的骨密度、原始刚度和原始强度。用配对t检验比较两组椎体的高度和生物力学性能在手术前、后的改变，其中椎体中线两侧高度差在手术前、后的改变用单因素方差分析。结果两组椎体的骨密度、原始强度和刚度之间差异无统计学意义（P〈0．05）。骨折后，椎体的前缘、中线和后缘高度均减少，刚度较原始刚度降低。单侧组平均注入3．07mLSrHAC，双侧组平均注入5．82mLSrHAC。术后椎体各部位的高度均有所增加，但未能恢复到原始高度水平。术后两组椎体中线两侧的高度及两组椎体强化后的强度差异均无统计学意义（P〉0．05）。两组椎体强化后的刚度均有一定程度的修复，双侧组较单侧组刚度修复效果好。结论单侧或双侧注射SrHAC行球囊扩张椎体后凸成形术均能修复骨折椎体模型的高度和生物力学性能。     

Effect of estrogen on intestinal strontium absorption in postmenopausal women

Objectives: there is considerable uncertainty about the underlying cause of decreased intestinal calcium absorption that occurs in postmenopausal women. In a previous study, estrogen treatment did not result in an increased intestinal calcium absorption using strontium as a marker. A possible explanation could be that the calcium/strontium load given to the women was too high (600 mg Ca), which might result in an insensitive test with respect to the possible stimulation of active strontium transport by estrogen. Therefore, the purpose of this study was to reinvestigate the effect of estrogen on active intestinal strontium absorption using a load of 2.5 mmol of strontium only. Methods: the effect of estrogen on intestinal strontium absorption was measured in eight normal postmenopausal women. The study included two baseline strontium absorption tests, which were performed with an interval of 10 days for calculating the within subject variation (SER). Thereafter the effect of 2 months of estrogen treatment on intestinal strontium absorption was assessed. Fractional absorption (FC₂₄₀) and the area under the concentration time curve (AUC) 4 h after an oral strontium load of 2.5 mmol were calculated. Results: the within subject SER of FC₂₄₀ and AUC^0-240 were 2.3±0.76 and 1.2±0.41, respectively. FC₂₄₀ and AUC^0-240 of strontium were unchanged after treatment with estrogen. Conclusions: in normal postmenopausal women, we did not find a modulating effect of short-term treatment with a (supra) physiological dose of estrogen on intestinal calcium absorption as measured by the strontium absorption test.     

Strontium transport in the rat colon

Summary Concentration dependence of strontium (Sr) fluxes across the colon ascendens and descendens of the rat were measured in a modified Ussing-chamber. Mucosa (m) to serosa (s) and s to m Sr fluxes across both colonic segments were linearly related to the Sr concentration from 0.125 mmol/l to 10 mmol/l. In the colon ascendens m to s Sr fluxes were slightly higher than the fluxes in the opposite direction, resulting in net Sr absorption. In the colon descendens s to m fluxes were higher than the ms fluxes, resulting in net Sr secretion. Neither Sr nor calcium (Ca) showed a concentration dependent interaction with respect to their unidirectional fluxes in both parts of the colon. Only in the colon ascendens Sr at the highest concentration (10 mmol/l) inhibited m to s calcium transport.Experiments, in which the voltage dependence of the unidirectional Sr fluxes was measured confirmed the results obtained from the concentration dependence: (1) The unidirectional fluxes of Sr across the colon ascendens and descendens were totally voltage dependent, i.e. diffusive. (2) In the colon descendens the voltage dependence of the s to m flux was steeper than the flux from m to s. It is hypothesized that this prevalence is caused by an anomalous solvent drag effect. 1.25-Dihydroxyvitamin D₃ [1.25 (OH)₂D₃] stimulated m to s calcium flux in the colon descendens but had no effect on Sr flux.The results demonstrate that Sr and Ca in the rat colon are transported by different mechanisms. In contrast to the Ca transport the Sr flux is only diffusive and insensitive to 1.25 (OH)₂D₃.Supported by the Deutsche Forschungsgemeinschaft SFB 38 Membranforschung Send offprint requests to U. Karbach at the above address     

Management of osteoporosis in the elderly

ABSTRACT

Background: Osteoporosis is predominantly a condition of the elderly, and the median age for hip fracture in women is approximately 83 years. Osteoporotic fracture risk is multifactorial, and often involves the balance between bone strength and propensity for falling.

Objective: To present an overview of the available evidence, located primarily by Medline searches up to April, 2009, for the different management strategies aimed at reducing the risk of falls and osteoporotic fractures in the elderly.

Results: Frailty is an independent predictor of falls, hip fractures, hospitalisation, disability and death in the elderly that is receiving increasing attention. Non-pharmacological strategies to reduce fall risk can prevent osteoporotic fractures. Exercise programmes, especially those involving high doses of exercise and incorporating balance training, have been shown to be effective. Many older people, especially the very elderly and those living in care institutions, have vitamin D inadequacy. In appropriate patients and given in sufficient doses, vitamin D and calcium supplementation is effective in reducing both falls and osteoporotic fractures, including hip fractures. Specific anti-osteoporosis drugs are underused, even in those most at risk of osteoporotic fracture. The evidence base for the efficacy of most such drugs in the elderly is incomplete, particularly with regard to nonvertebral and hip fractures. The evidence base is perhaps most complete for the relatively recently introduced drug, strontium ranelate. Non-adherence to treatment is a substantial problem, and may be exacerbated by the requirements for safe oral administration of bisphosphonates.

Conclusion: Evidence-based strategies are available for reducing osteoporotic fracture risk in the elderly, and include exercise training, vitamin D and calcium supplementation, and use of evidence-based anti-osteoporotic drugs. A positive and determined approach to optimising the use of such strategies could reduce the burden of osteoporotic fractures in this high-risk group.     

锶与人体健康

锶是人体中必需微量元素之一,它与人体骨骼的形成密切相关,是骨骼、牙齿的主要成分,身体所有组织中都有锶,在肠内它与钠竞争吸收部位,使人体降低对钠的吸收,有利于心血管正常活动。锶可用来治疗一些由于副甲状腺功能不全导致的抽搐症状,缺锶会引起龋齿,锶过量则可引起骨骼的生长发育过快,表现为关节和骨骼变形、粗大、脆弱、疼痛,肌肉萎缩及贫血等。     

雷奈酸锶治疗骨质疏松症的疗效及安全性的Meta分析

目的系统评价雷奈酸锶治疗骨质疏松症的疗效及安全性。方法检索Cochrane的RCT中心数据库、Embase、PubMed、CNKI数据库和维普数据库中雷奈酸锶治疗骨质疏松症的临床研究,按照纳入及排除标准筛选出随机对照试验,使用"Cochrane协作网的偏倚评论指标"评估搜集的文献质量。提取有效数据,采用RevMan 5.3软件进行Meta分析。结果共纳入双盲、随机对照试验6项,结果表明,雷奈酸锶治疗12个月后,腰椎、髋部及股骨颈骨密度提升度比安慰剂对照组分别高6.72%(95%CI:6.17%~7.27%,P<0.01)、3.97%(95%CI:3.53%~4.40%,P<0.01)及3.51%(95%CI:3.21%~3.81%,P<0.01)。雷奈酸锶组的不良反应发生率、因不良反应导致的患者退出率和安慰剂组相似,差异无统计学意义(P>0.05);雷奈酸锶组的皮肤和胃肠道不良反应事件发生率高于安慰剂组,差异有统计学意义(P<0.05)。结论相对于安慰剂对照,雷奈酸锶可显著提高腰椎、髋部及股骨颈骨密度,两者的安全性近似。     

Shh在雷奈酸锶促进骨髓间充质干细胞成骨分化过程中的作用

 目的：研究Sonic Hedgehog（Shh）在雷奈酸锶（strontium ranelate,Sr）促进大鼠骨髓间充质干细胞（BMSCs）向成骨细胞分化中的作用。方法：采用全骨髓贴壁培养法分离、纯化、培养大鼠BMSCs,取第3~5代BMSCs加入成骨诱导液诱导成骨分化,再加入不同浓度Sr及Shh拮抗剂cyclopamine（Cy）,分别观察它们对BMSCs向成骨细胞分化的影响。酶标法检测成骨细胞分化早期标志物碱性磷酸酶(alkaline phosphatase,ALP)的活性;茜素红染色检测细胞钙化水平;Western blotting法检测Shh和Runx2蛋白的表达情况。结果：Sr（3 mmol/L）可以使细胞ALP活性增高,钙结节形成增加。Sr（0.1～5 mmol/L）作用BMSCs 7 d,可明显促进Shh和Runx2蛋白的表达,且Shh蛋白在1 mmol/L Sr作用时表达最多,而Runx2在3 mmol/L Sr作用时表达最多。1 mmol/L Sr作用BMSCs不同时间（1、3、5、7 d）,呈时间依赖性地上调Shh和Runx2蛋白的表达。Cy（10 μmol/L）不仅拮抗Sr对Shh和Runx2表达的上调作用,还抑制Sr对ALP和钙结节形成的促进作用。结论：Sr可通过上调Shh蛋白及成骨特异性转录因子Runx2的表达促进BMSCs向成骨细胞分化。     

Hemorheological changes with strontium ranelate treatment do not seem to be related to its claimed prothrombotic effects

Strontium ranelate is claimed to be related with increased risk of thromboembolic events. No explanation of this increased incidence of thromboembolism has been identified. However, growing evidence has clearly demonstrated the involvement of blood rheology in any thrombotic process. The aim of this study was to assess hemorheological changes with strontium ranelate treatment in elderly women with osteoporosis. This study was designed in a prospective manner. Twenty-two elderly women diagnosed with osteoporosis were included. During a 2-month treatment period, participants received strontium ranelate 2 g/day. Hemorheological parameters including erythrocyte deformability, erythrocyte aggregation and plasma viscosity were measured before and after 2 months therapy with strontium ranelate. The median age of the patients was 70.0 (range = 65-80) years. After 60 days of treatment, there was no statistically significant change in hemorheological parameters. None of the subjects developed clinical venous thromboembolic event (VTE) during the 2-month period of strontium ranelate treatment. Our study demonstrated that in elderly women, treatment of osteoporosis with strontium ranelate did not change hemorheological parameters over 2 months of time. However, its long-term effects on hemorheologic parameters should be evaluated further with a larger sample.