Long-term treatment of osteoporosis in postmenopausal women: a review from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF)

Abstract

Introduction:

Postmenopausal osteoporosis is a chronic disease requiring treatment that balances long-term fracture efficacy against risk.     

Relationship between change in femoral neck bone mineral density and hip fracture incidence during treatment with strontium ranelate

ABSTRACT

Objective: Strontium ranelate (SR) increases bone mineral density (BMD) in postmenopausal osteoporotic women and reduces vertebral and non-vertebral fracture incidence. Hip fracture reduction has also been observed during 3-year treatment with SR in osteoporotic women at high risk of hip fracture. The objective of this study is to analyse the association between BMD changes and hip fracture incidence during treatment with SR.

Material and methods: In this post-hoc analysis, 465 women aged over 74 years with low BMD at the femoral neck (T-score ≤ –2.4 according to NHANES normative values) were selected from the population of a recently published study (the Treatment of Peripheral Osteoporosis Study – TROPOS). BMD was assessed at the femoral neck at baseline and after a follow-up of 3 years. Hip fractures were reported by study investigators.

Results: After adjusting for age, body mass index, femoral neck BMD at baseline and number of prevalent vertebral fractures, we found that for each 1% increase in femoral neck BMD observed after 3 years, the risk to experience a hip fracture after 3 years decreased by 7% (95% CI: 1–14%) (?p = 0.04). In patients experiencing a hip fracture over 3 years of treatment with SR, femoral neck BMD increased by (mean [SE]) 3.41 (1.02)% compared to 7.23 (0.81)% in patients without hip fracture (?p = 0.02).

Conclusion: In this post-hoc analysis of women undergoing 3 years of SR treatment, an increase in femoral neck BMD is associated with a decrease in hip fracture incidence.     

老年人髋部骨折与骨质疏松发病率的相关性研究

目的探讨老年人髋部骨折与骨质疏松发病率的相关性。方法选取本院2011年2月～2013年2月诊治的髋部骨折老年患者91例,均为单侧骨折。将健侧作为对照组,将髋部骨折侧作为观察组,分别行骨密度测定,分析老年人髋部骨折与骨质疏松发病率的相关性。结果依60岁～、66岁～、〉71岁的顺序,老年髋部骨折患者两侧骨密度均不同程度地下降。健侧骨密度明显高于患侧骨密度,差异有统计学意义（P〈0.05）。依60岁～、66岁～、〉71岁的顺序,老年髋部骨折患者骨质疏松发病率明显升高,差异有统计学意义（P〈0.05）。Pearson相关性分析显示老年患者髋部骨折与骨质疏松发病率存在显著的正相关性（r=0.419,P=0.012）。结论老年人髋部骨折与骨质疏松发病率存在明显的正相关性,骨质疏松发病率越高,老年人髋部骨折发生率越高。     

Prevalence of vitamin D inadequacy in Scottish adults with non-vertebral fragility fractures

ABSTRACT

Background: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age, or below the normal range.

Objectives: To investigate the prevalence of vitamin D inadequacy in an elderly population presenting to the South Glasgow Fracture Liaison Service with non-vertebral fragility fractures in order to assess the extent of the problem.

Research design and methods: The retrospective arm of this study used data from an established database to identify patients aged over 50 years admitted to South Glasgow University Hospitals over the previous 4 years with hip fracture. The prospective arm identified the first 50 patients aged over 50 presenting with a clinical non-vertebral fragility fracture with osteoporosis as measured by axial spine and/or hip DEXA (T‐score < –2.5) after November 2004.

Results: In the retrospective arm, 626 patients were identified from the database: mean age 80.5 years; 94% were aged over 60 and 74% were aged over 75. Data analysis was limited to 548 patients aged over 60 years with vitamin D recordings and not receiving supplementation with calcium and vitamin D. The mean vitamin D level was 24.7?nmol/L (9.9?ng/ml) SD = 17, however, it is likely that the true mean is lower since in approximately 25% of cases vitamin D levels were reported as < 15?nmol/L (effectively unrecordable). These were transcribed as 15?nmol/L in order to permit a numerical value to be calculated. In the absence of an agreement on what should constitute a diagnostic serum level of vitamin D inadequacy, a number of thresholds were considered – 97.8% had vitamin D levels below 70?nmol/L and 91.6% had vitamin D levels below 50?nmol/L. There were no significant differences by patient sex, age or season of presentation.

The mean age of patients in the prospective arm was 65.8 years (range 50.6–83.8), 72% were aged over 60 and 16% were aged over 75. The mean vitamin D level was 44.1?nmol/L (18.4?ng/ml) SD = 25.3; 82% had vitamin D levels below 70?nmol/L and 72% had vitamin D levels below 50?nmol/L. Although numbers were too small to justify extensive subgroup analyses, the mean vitamin D level in the 13 patients with hip fracture (34.5?nmol/L) was lower than in the 37 with non-hip fractures (48.2?nmol/L).

Conclusions: This study confirms almost universal vitamin D inadequacy among 548 elderly patients admitted to hospital with hip fracture, regardless of whether a threshold of 50?nmol/L or 70?nmol/L was used. However, among a prospective subset of 50 patients with clinical fragility fractures, especially those with non-hip fractures, the prevalence of inadequacy was substantially lower. It may be that vitamin D represents a correctable risk factor for fragility fracture in the elderly, possibly specifically for the hip.     

雷奈酸锶的合成

目的研究雷奈酸锶的化学合成。方法以无水柠檬酸为起始原料,经脱羧、酯化、环合、烷基化、水解和成盐等多步反应生成最终产物雷奈酸锶。结果雷奈酸锶的结构经IR1、H-NMR1、3C-NMR得到证实,总产率为41.4%。结论本合成路线操作简单,成本低,纯度高,适合工业化生产。     

骨质疏松性髋部骨折的治疗

目的提高髋部脆性骨折治愈率,降低伤残率。方法对108例髋部脆性骨折患者资料进行回顾性分析,平均随访23个月。探讨Singh分级、治疗措施与预后的关系。结果①SinghⅢ～Ⅵ级者行内固定术,Ⅰ～Ⅱ级者行人工关节置换,优良率为83．3％;②内固定与人工关节置换的并发症发生率分别为11．4％、7．9％（P〉0.05）;③脆性骨折经口服阿仑膦酸钠5个月后,94．4％的患者Singh分级不变;④预防使用抗生素由平均6．9d减为1．7d,术后感染未增多（P〈0.05）。结论Singh指数为基层医院了解股骨近端骨质疏松程度的一种方法;内固定或人工关节置换治疗高龄髋部脆性骨折,并发症不少;脆性骨折术后应使用阿仑膦酸钠;限制使用抗生素不会增加骨科内植物术后感染率。     

骨吸收抑制剂治疗绝经后骨质疏松的临床评价

目的　评价不同类型骨吸收抑制剂在临床原发性骨质疏松症治疗中的疗效。方法　30 0例原发性骨质疏松症患者分成三组 ,每组 10 0例 ,所有患者均排除继发性骨质疏松。性激素类组 :服用利维爱 2 5mg ,隔日 1次 ;降钙素组 :密钙息 5 0IU ,肌注 ,第 1周每天 1次 ,第 2周隔日 1次 ,以后每周 2次 ;二膦酸盐组 :阿仑膦酸钠 10mg ,每天 1次。治疗 2年后随访 :腰椎骨密度 (BMD)、胫骨骨超声 (QUS)、尿羟脯氨酸 (HOP)、骨钙素和新骨折。结果　临床骨痛降钙素缓解速度最快 ,性激素类药物可迅速有效地缓解妇女更年期症状。治疗 2年后 ,腰椎骨密度明显上升 (P <0 0 5 ) ,二膦酸盐组上升 5 1% ,性激素类组上升 4 2 % ,降钙素上升 0 97% ;胫骨骨超声显著提高 (P <0 0 5 ) ,性激素组上升 2 1% ,降钙素组 1 8% ,二膦酸盐组 1 7% ;新骨折共 4例 :二膦酸盐组 2例 ,降钙素组和性激素组各 1例 ;尿羟脯氨酸仅二膦酸盐组明显下降 ;骨钙素各组无明显变化。结论　骨吸收抑制剂是骨质疏松治疗的重要手段 ,性激素类药物是治疗伴有绝经后综合症骨质疏松患者的首选药物 ,二膦酸盐对骨量较低且伴有骨痛的患者有良好的疗效 ,降钙素治疗骨质疏松疼痛临床疗效显著。     

老年住院患者衰弱指数与血清25羟维生素D关系的研究

目的 探讨老年住院患者衰弱指数与血清25羟维生素D水平的相关性.方法 选择老年住院患者100例,依据老年综合评估构建衰弱指数(frailty index based on a Comprehensive Geriatric Assessment,FI-CGA);抽取静脉血标本,测定血清25羟维生素D[25(OH)D]水平;依据25 (OH)D水平将研究人群分为严重缺乏组、缺乏组、不足组和充足组.结果 本研究人群FI-CGA的中位数(四分位数间距)为0.172(0.096～0.216),与维生素D缺乏组[0.154(0.103～0.196)]、不足组[0.107(0.085～0.155)]和充足组[0.071(0.066～0.073)]相比,维生素D严重缺乏组[0.234(0.133～0.367)]的FI-CGA显著升高;Spearman相关分析显示FI-CGA与25 (OH)D呈负相关(r=-0.499,P＜0.001).有序多分类Logistic回归分析结果显示25 (OH)D是FI-CGA的独立保护因素(P＜0.001).结论 老年住院患者中,衰弱指数与维生素D、年龄、性别相关,应注重高龄、女性患者的衰弱筛查,适量补充维生素D可能成为预防和治疗衰弱的一种有效手段.     

Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London

ABSTRACT

Background: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age,?or below the normal range.

Objectives: To investigate the prevalence of vitamin D inadequacy in an elderly population with hip fractures from London (UK) and compare levels with data previously presented from Glasgow (UK).

Research design and methods: A retrospective patient audit was carried out over a 17‐month period (September 2003–January 2005). Patient records were searched for hip fracture admissions and cross matched with vitamin D analysis carried out within 3 days of the hip fracture admission. The resulting records were hand searched to exclude patients with a hip fracture resulting from high impact/trauma.

Results: There were data for 103 hip fracture patients, 79.6% of the patients were women (n = 82). The mean age at the time of fracture was 73.4 years, 100% were aged 60 years or over and 41% were aged 75 years or over. Around 20% of the patients were receiving supplementation with calcium and/or vitamin D and were not excluded from the analysis. The mean vitamin D level was 32.1?nmol/L (12.9?ng/mL), SD = 19.4 (7.8), however, it is likely that the true mean is lower since in approximately 15% of cases vitamin D levels were reported as < 12.5?nmol/L, but were transcribed at 12.5?nmol/L in order to allow a numerical value to be calculated. Ninety-nine per cent of patients had a vitamin D level < 80?nmol/L, 94.2% < 70?nmol/L and 81.6% < 50?nmol/L.

There were no significant differences by patient age or sex, however, there were significant seasonal differences in vitamin D. In the year from September 2003 to August 2004, 82.8% of summer admissions had vitamin D levels < 70?nmol/L compared with 98.0% in winter (?p = 0.04). Mean vitamin D levels in the 30 patients with parathyroid hormone (PTH) levels above the reference range were significantly lower than levels in the 71 patients within the range: mean 19.9?nmol/L, SD = 16.2 versus mean 37.5?nmol/L, SD = 18.5 (?p < 0.0001). Furthermore, 50% of the patients with PTH levels above the reference range had vitamin D levels < 12.5?nmol/L, reflecting extremely low levels of vitamin D.

Conclusions: This study confirms almost universal vitamin D inadequacy among 103 patients admitted to hospital with hip fracture in London, although the prevalence of inadequacy is slightly lower than that seen in a similar study carried out in Glasgow.     

髋部骨密度和几何结构与老年妇女髋部骨折关系的研究

目的 探讨老年妇女髋部骨折与髋部骨密度（BMD）和股骨近端几何结构的关系。方法 髋部骨质疏松骨折的妇女57例和无骨折妇女60例，测量腰椎，股骨近端骨密度及股骨颈轴长（FNAL），颈干角（NSA）（髋部骨折组对其健侧进行检测），比较，提示彼此间的相关性。结果 老年妇女髋部骨折患者与对照组比较；股骨近端骨密度明显降低，FNAL长于对照组，NSA较对照组大。结论 股骨近端骨密度和FNAL及NSA可以提高对老年妇女髋部骨质疏松骨折危险性的预测。     

雷奈酸锶对大鼠应力缺失性骨丢失的防治作用

摘要： 目的 探讨雷奈酸锶对尾悬吊导致的应力缺失性大鼠骨质疏松的防治效果。方法 6 月龄 SD 大鼠 30 只, 随机均分为 3 组： 正常对照组（A 组）、 尾悬吊组（B 组）、 雷奈酸锶干预组（C 组）。B、 C 两组大鼠采用尾悬吊法制 备应力缺失型骨质疏松大鼠模型, C 组给予 1 g/(kg·d） 雷奈酸锶干预, 4 周后处死所有大鼠, 取左侧股骨检测骨密度, 取左侧胫骨制备非脱钙组织切片并行骨形态计量学检测, 取右侧股骨和胫骨骨髓细胞体外培养并向成骨细胞诱导 分化, 取第 4 代细胞及血清检测骨钙素 （OCN） 的表达。结果 B 组骨密度低于 A 组, C 组高于 B 组 （P＜0.05）。 B 组 骨小梁体积（BV/TV）、 骨小梁数量（Tb.N）、 骨小梁厚度（Tb.Th）低于 A、 C 组, 破骨细胞数（Oc.N）、 骨吸收长度比（Er. Pm）高于 A 组, C 组骨形成率（BFR/BV）、 矿化长度比（L.Pm）高于 B 组, Er.Pm、 Oc.N 低于 B 组（P＜0.05）。B、 C 组 OCN mRNA 表达水平高于 A 组, 但血清中 OCN 水平 B 组低于 A、 C 组 （P＜0.05）。结论 尾悬吊 4 周可造成大鼠骨 丢失, 雷奈酸锶可抑制其骨量丢失, 作用机制可能与其通过上调 OCN 的表达促进骨形成有关。     

European women's preference for osteoporosis treatment: influence of clinical effectiveness and dosing frequency

ABSTRACT

Objective: To determine participant preference for weekly versus monthly bisphosphonate therapy for osteoporosis after being informed about differences in fracture efficacy.

Design: 20‐minute, semi-structured, face-to-face or telephone interviews. Two bisphosphonate choices were presented on the basis of block randomization: weekly therapy with proven efficacy to reduce fracture risk at the spine and hip, or monthly therapy with proven efficacy to reduce fracture risk at the spine but not the hip.

Subjects: Women from the UK, Germany, France, Spain and Italy, with postmenopausal osteoporosis and aged ≥ 55 years. Fifty percent were currently taking a weekly bisphosphonate; 50% had no history of taking any bisphosphonate.

Measures: An efficacy rating scale and an intention-to-use rating scale were developed for this study. The primary endpoint was preference for weekly or monthly therapy. Reasons for preference were recorded.

Results: A preference was recorded for 1248 women (1253 were recruited). More women preferred weekly to monthly therapy (82% vs. 18%, respectively; p < 0.001). Among women who preferred weekly therapy, efficacy was the most commonly cited reason (65%). Ninety-two percent of the total cohort rated the efficacy of the weekly therapy as ‘excellent/good’ versus 38% for monthly (?p < 0.001). Sixty-nine percent intended to use weekly bisphosphonates compared with 34% for monthly (?p < 0.001).

Conclusions: When informed about differences in fracture efficacy in weekly and monthly bisphosphonates, a significantly greater proportion (82%) of women preferred a weekly bisphosphonate with proven fracture efficacy at the spine and hip over a monthly bisphosphonate with proven fracture efficacy only at the spine.     

Incadronate inhibits osteoporosis in ovariectomized rats

Incadronate is a highly effective inhibitor of stimulated bone resorption as demonstrated in a hypercalcemia model in rats, bone metastasis models in mice and rats, and an osteoporosis model in dogs. In this study, the effect of incadronate on osteoporosis in ovariectomized rats was examined. Incadronate dose-dependently inhibited decreases in second lumbar vertebrae bone mineral density (BMD) following oral administration for 4 or 12 weeks. Significant inhibition was observed at doses of more than 0.3 mg/kg. Incadronate dose-dependently inhibited the loss of distal femur metaphyseal compressive strength following 12 weeks of oral administration, and this was significant at a 3 mg/kg daily dose. Incadronate also dose-dependently inhibited the increases in urinary deoxypyridinoline levels after 4-or 12-week oral administrations. While incadronate had no effect on serum osteocalcin levels after 4 weeks of oral administration, it did dose-dependently reduce levels after 12 weeks of oral administration. These results suggested that incadronate may be a useful drug for osteoporosis due to stimulated bone resorption.     

New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion

ABSTRACT

Background: Adequate vitamin D and calcium nutrition play a critical role in the maintenance of musculoskeletal health and are considered the first step in osteoporosis treatment.

Roundtable discussion: In February 2008 Merck Sharp & Dohme sponsored a 2-day, evidence-based expert panel on the benefits of vitamin D for the patient with osteoporosis and the role of vitamin D in combination with antiresorptive therapy for the management of osteo­porosis. One of the primary objectives of the meeting was to review new data on the optimal serum 25-hydroxy­vitamin D [25(OH)D]levels. The symposium was attended by 29 researchers and clinicians from Europe and the Middle East. The discussion focused on optimizing vitamin D and calcium nutrition and reducing falls and fractures in osteoporotic patients.

Conclusions: Current evidence and expert opinion suggests that optimal serum 25(OH)Dconcentrations should be at least 50?nmol/L (20?ng/mL) in all individuals. This implies a population mean close to 75?nmol/L (30?ng/mL). In order to achieve this level, vitamin D intake of at least 20?µg daily is required. There is a wider thera­peutic window for vitamin D than previously believed, and doses of 800?IU per day, regardless of sun exposure, season or additional multivitamin use, appear to present little risk of toxicity. Apart from fracture and fall preven­tion, optimization of vitamin D status may also have additional general health benefits. Based on newly emerging data regarding calcium supplementation, and recommendations for increased vitamin D intake, the current recommendations for calcium intake in postmenopausal women may be unnecessarily high. In addition to vitamin D and calcium, treatment of patients with osteo­porosis at high risk of fractures should also include pharmacologic agents with proven vertebral and non-vertebral fracture efficacy.     

老年与青年骨内无机及微量元素分布比较

研究老年髋部骨折病人松质骨内无机及微量元素含量。方法应用质子激发Ｘ射线荧光分析技术测定１２只股骨头松质骨中无机及微量元素含量,其中青年组５例,老年组７例。结论测定老年人骨内微量元素含量可能对预测髋部骨折及骨质疏松症的疗效评价等有一定临床价值。     

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。     

An overview of the prevalence of 25‐hydroxy-vitamin D inadequacy amongst elderly patients with or without fragility fracture in the United Kingdom

ABSTRACT

Background: Many studies have investigated the prevalence of 25-hydroxy-vitamin D inadequacy throughout the world and found a high prevalence of 25-hydroxy-vitamin D inadequacy in older patients, particularly those with fragility fracture.

Scope: To review the findings from vitamin D audits from six units across the UK and compare with previously published data from around the world. Results from four units have been previously published (Belfast, Glasgow, London and Medway) and this paper presents new data from Southampton and Carshalton, and further sub-analysis of the data from Medway.

Findings: Three audits of patients attending metabolic bone clinics (Carshalton, Medway and Southampton) identified 954 patients, of which overall 49% had a prior fragility fracture. Mean 25‐hydroxy-vitamin D levels ranged from 47.7?nmol/L to 62.4?nmol/L. Of these patients 72.9–88.9% had a 25‐hydroxy-vitamin D level < 80?nmol/L, 68.8–83.3% < 70?nmol/L and 37.5–59.1% < 50?nmol/L. The mean age of patients ranged from 60.0 to 67.5 years. Sub-analysis of the data by fracture status revealed that patients with fracture had lower mean levels of 25‐hydroxy-vitamin D compared with patients without fracture. This was statistically significant in the sub-analysis of the Medway data (45.3?nmol/L versus 49.9?nmol/L, p < 0.005).

Three audits identified 330 patients with fragility fracture. Audits from Glasgow and Belfast specifically identified patients with fragility fracture. A subgroup of patients with fracture aged over 50 years from the Medway audit was also included in this group. Mean levels of 25‐hydroxy-vitamin D ranged from 40.0?nmol/L to 52.3?nmol/L. 83.7–96.4% of patients had a 25‐hydroxy-vitamin D level < 80?nmol/L, 73.3–89.7% < 70?nmol/L and 55.8–73.2% < 50?nmol/L. The mean age of patients ranged from 65.3 to 68.6 years.

The audits carried out in Belfast and Medway were also divided by supplementation status. Mean 25‐hydroxy-vitamin D levels were 48.1?nmol/L in Belfast and 40.5?nmol/L in Medway in the patients not receiving supplements and 53.8?nmol/L and 59.9?nmol/L, respectively in the patients receiving supplements. The difference was statistically significant in the Medway audit (?p < 0.0001), but not in the smaller Belfast audit (?p = 0.216). As would be expected, the prevalence of 25‐hydroxy-vitamin D inadequacy was higher in the patients not receiving supplements, for example at the 70?nmol/L threshold: 82.6% versus 67.1% in Belfast and 89.6% versus 72.7% in Medway.

Three audits specifically identified 694 patients with hip fracture (Belfast, Glasgow and London). Mean levels of 25‐hydroxy-vitamin D ranged from 24.7?nmol/L to 36.1?nmol/L. Of these patients 90.7–99.0% had a 25‐hydroxy-vitamin D level < 80?nmol/L, 88.4–98.0% < 70?nmol/L and 81.6–92.7% < 50?nmol/L. The mean age of patients ranged from 73.4 to 80.5 years.

Conclusion: Inadequate 25‐hydroxy-vitamin D levels are extremely common in the elderly and particularly so in patients with fragility fracture – specifically in those with hip fracture. Although the differing audit specifications and assay techniques used make direct comparisons difficult, the data do provide a snapshot of 25‐hydroxy-vitamin D status across the UK and are consistent with those previously observed elsewhere in Europe and the rest of the world.     

骨质疏松致脊椎骨折53例疗效分析

目的 探讨骨质疏松致脊椎骨折的病理过程，以取得最佳诊断和治疗。方法 对具有完整临床资料的骨质疏松症53例病例，重点对诊断、防治进行分析和研究，归纳总结经验教训。结果 患者在接受缓急轻重的计划治疗后，达到了早期愈合和康复目的．优良率92％。结论 诊疗过程中．应防止误诊，如果处理不当，预后不良，甚至发生死亡，死亡率约为20％。死亡原因往往并非骨折本身，而是卧床休息引起的并发症。治疗中的矛盾，必须用综合兼顾、相互协调等措施来解决，才能取得最佳疗效。