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

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-hydroxy vitamin 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)D concentrations 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 microg 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.     

Phase IV randomized preference study in patients eligible for calcium and vitamin D supplementation

Introduction/objectives: Preference for supplement formulation helps determine an individual’s adherence to long-term medication and can improve clinical benefit for chronic illnesses such as osteoporosis. This study compared the preference, acceptability and tolerability of a reformulation of Calcichew D3¹ 500?mg/400?IU and Calcichew D3 500?mg/800?IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D3² 500?mg/400?IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500?mg/800?IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively.

Method: This phase IV, randomized, open-label, two-period, cross-over study was conducted at nine sites in the UK and Germany. Eligible subjects (≥65 years requiring calcium/vitamin D supplementation for prevention/treatment of deficiencies, or ≥18 years requiring supplementation as an adjunct to osteoporosis treatment) were randomly assigned to one of two 2 week treatment sequences – Group 1: Calcichew D3 500/400 then Adcal-D3 500/400 (or vice versa), or Group 2: Calcichew D3 500/800 then Kalcipos-D 500/800 (or vice versa). After each treatment period, patients rated the treatment for acceptability using 100?mm visual analogue scales. After the second treatment period, patients indicated their treatment preference. The primary endpoint, the percentage of patients with a preference for each treatment, was analyzed with a logistic regression model.

Results: Two hundred and seventy-six patients were randomly assigned by treatment sequence, 138 to each group. Preference questionnaires among patients who preferred Calcichew or comparator revealed the odds for patients preferring Calcichew 500/400 (77.6%) over Adcal-D3 was 3.46 ([95% CI 2.24, 5.36], p?<?0.001) in Group 1, and Calcichew D3 500/800 (63.2%) over Kalcipos-D was 1.72 ([1.19, 2.47], p?=?0.004) in Group 2. Adverse events were mostly gastrointestinal and were comparable between groups. The new formulation of Calcichew D3 is acceptable and consistent with its known tolerability profile.

Conclusions: In this short-term 30?day study, patients preferred Calcichew D3 500/400 and Calcichew D3 500/800 over respective comparators. A trend towards better compliance with Calcichew D3 preference observed in Group 1 warrants a longer term study to identify treatment compliance.

Trial registration: Clinicaltrials.gov: NCT02457247.     

葡萄糖酸钙联合维生素D和骨肽辅助治疗老年性骨折的临床疗效观察

目的探讨葡萄糖酸钙联合维生素D和骨肽辅助治疗老年性骨折的临床效果。方法选择本院2007年2月～2012年7月收治的100例老年性骨折患者为研究对象,随机分为两组。对照组给予常规药物治疗,治疗组在常规治疗的基础上给予葡萄糖酸钙联合维生素D和骨肽辅助治疗。治疗后,比较两组有效率、骨密度以及住院时间、骨折愈合时间等。结果治疗组患者有效率、骨密度、住院时间以及骨折愈合时间均优于对照组,差异有统计学意义（P〈0.05）。治疗组方案安全性较好,治疗期间未见与葡萄糖酸钙、骨肽等相关的严重不良反应。结论葡萄糖酸钙联合维生素D和骨肽辅助治疗老年性骨折能加速患者康复,提高骨密度,具有较好的临床安全性,值得推广应用。     

The vitamin D metabolites in the pathogenesis and management of osteoporosis

Summary

Studies on post-menopausal osteoporotic patients indicate that 1,25-(OH)₂D₃ concentrations are no different from those in age-matched normal subjects and the data suggest that the malabsorption of calcium found in many osteoporotic patients cannot generally be attributed to low plasma 1,25-(OH)₂D₃ levels. The effects are discussed of three different therapies - sex hormones alone, vitamin D metabolites alone and a combination of both - on calcium balance and peripheral bone loss in treated compared with untreated osteoporotic patients. The results indicate that combined therapy with a vitamin D metabolite and an oestrogen is more effective in inhibiting the rate of bone resorption in post-menopausal osteoporosis than treatment with either agent used alone, and should be regarded as the treatment of choice at the present time. It is suggested that, using this regimen which is suitable for patients up to about 65 years of age, calcium supplementation is not required, provided daily calcium intake is reasonably adequate, and may even be undesirable by increasing the risk of hypercalcaemia.     

阿仑膦酸钠联合碳酸钙D3治疗糖尿病性骨质疏松症疗效分析

目的观察阿仑膦酸钠（ALN）联合碳酸钙D3与单独使用碳酸钙D3治疗糖尿病性骨质疏松（DOP）的临床疗效与安全性。方法对46例DOP患者的临床病例资料进行回顾性分析,将其随机分为治疗组和对照组各23例,治疗组采用阿仑膦酸钠联合碳酸钙D3治疗,对照组单独使用碳酸钙D3治疗,比较两组治疗前后前臂远端骨密度（BMD）值。结果两组患者BMD值均有所增加,与治疗前比较改善差异均有统计学意义（P〈0.05）;而治疗组BMD值增加更为明显,与对照组相比,差异亦具有统计学意义（P〈0.05）。结论 ALN联合碳酸钙D3治疗DOP,患者BMD值增加更快,疼痛等症状改善明显,效果优于碳酸钙D3的单独使用。     

Prevalence of vitamin D inadequacy in European postmenopausal women

ABSTRACT

Objective: Inadequate vitamin D level is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to assess the prevalence of inadequate serum vitamin D levels in postmenopausal European women. There are no clear international agreements on what constitutes a level of vitamin D inadequacy, but recent publications suggest that the circulating level of vitamin D should be over 80?nmol/L or at least between 50 and 80?nmol/L.

Material and methods: Assessment of 25-hydroxyvitamin D [25(OH)D] was performed in 8532 European postmenopausal women with osteoporosis or osteopenia. European countries included France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-offs of 25(OH)D inadequacy were fixed : < 80?nmol/L and < 50?nmol/L.

Results: Mean (SD) age of the patients was 74.2 (7.1) years, body mass index was 25.7 (4.1)?kg/m². Level of 25(OH)D was 61.0 (27.2)?nmol/L. There was a highly significant difference of 25(OH)D level across European countries (?p < 0.0001). The lowest level of 25(OH)D was found in France [51.5 (26.1)?nmol/L] and the highest in Spain [85.2 (33.3)?nmol/L]. In the whole study population, the prevalence of 25(OH)D inadequacy was 79.6% and 32.1% when considering cut-offs of 80 and 50?nmol/L, respectively and when considering patients aged less than 65 years, the prevalence reached 86% (cut-off of 80?nmol/L) and 45% (cut-off of 50?nmol/L).

Conclusion: This study indicates a high prevalence of vitamin D [25(OH)D] inadequacy in European postmeno­pausal women. The prevalence could be even higher in some particular countries. A greater awareness of the importance of vitamin D inadequacy is needed to address this public health problem.     

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.     

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.     

维生素D3滴剂囗服预防佝偻病的临床观察

目的探讨维生素D3滴剂囗服预防佝偻病的临床疗效。方法 70例维生素D缺乏性佝偻病患儿,随机分成对照组和观察组。对照组使用葡萄糖酸钙片。观察组使用葡萄糖酸钙片联合维生素D3滴剂。结果观察组显效率85.72%高于对照组62.86%,差异具有统计学意义（P〈0.05）。观察组BALP正常率88.57%优于对照组65.72%,差异具有统计学意义（P〈0.05）。结论维生素D3滴剂能有效治疗及预防佝偻病。     

维生素D3和葡萄糖酸钙治疗学龄前期佝偻病血生化指标分析

目的 :观察维生素D3 和葡萄糖酸钙对佝偻病的治疗作用。方法 :把佝偻病患儿分为非药物治疗对照组 (Ⅰ )、维生素D3治疗组 (Ⅱ )和维生素D3 加葡萄糖酸钙治疗组 (Ⅲ ) ,分别测定治疗前后血钙 (Ca)、磷 (P)、镁 (Mg)、碱性磷酸酶 (TALP)。结果 :佝偻病患儿Ⅱ、Ⅲ组治疗后 ,血Ca、P、Mg有所提高 ,TALP明显降低 ,并以Ⅲ组为明显 ,Ⅰ、Ⅱ、Ⅲ组治疗前后各指标经t检验差异有显著性(P<0 01)。结论 :维生素D3 葡萄糖酸钙对佝偻病都有较好治疗作用 ,两药联合使用 ,效果更好。维生素D3 和葡萄糖酸钙在防治佝偻病方面存在协同作用     

骨肽联合葡萄糖酸钙治疗骨质疏松症的临床观察

目的 探讨骨肽联合葡萄糖酸钙治疗骨质疏松症的临床效果.方法 选择2013年1～11月本院收治的120例骨质疏松症患者为研究对象,随机分为观察组和治疗组各60例,对照组患者给予非甾体消炎镇痛药物和钙剂口服,同时给予补充维生素D.观察组患者在对照组治疗基础上给予骨肽（50 mg）＋250 ml 0.9％NaCl注射液以及葡萄糖酸钙（10％,20 ml）＋250 ml 5％葡萄糖注射液静脉滴注,治疗2个月后观察比较两组患者的骨痛改善情况、腰椎和左侧股骨颈骨密度的变化情况.结果 观察组患者治疗总有效率（90.00％）明显高于对照组（56.67％）,差异有统计学意义（P＜0.05）;观察组治疗后腰椎L2-4骨密度水平为（0.78±0.10） g/cm2,左侧股骨颈骨密度水平为（0.58±0.02） g/cm2,均明显高于对照组,差异有统计学意义（P＜0.05）;两组不良反应发生率差异无统计学意义（P＞0.05）.结论 骨肽联合葡萄糖酸钙治疗骨质疏松症效果较好,能有效改善骨痛,提高骨密度,值得临床推广应用.     

The biochemical basis of renal osteodystrophy and post-menopausal osteoporosis: a view from the vitamin D system

Summary

The vitamin D endocrine system is now known to play an essential role in the regulation of plasma calcium and phosphorus concentrations and in overall organismal calcium economy. These two basic functions of the vitamin D endocrine system have provided important new insight into several disease states. The two disease states discussed here are the genesis of renal osteodystrophy and of post-menopausal osteoporosis. It seems likely that defects or alternations in the vitamin D system play important roles in the development of these disease states. Successful treatment undoubtedly will involve the vitamin D system and most likely the active form of vitamin D, 1,25-(OH)₂D₃.     

69例维生素D过量病例的血清维生素D与钙及钙磷乘积的关系

目的 分析69例维生素D过量病例的血清25-羟基维生素D[25-(OH)D]水平、血清钙及钙磷乘积(CPP)的关系.方法 血清25-(OH)D水平采用酶联免疫法检测,收集2009年至2011年2、3、9、10月份本医疗中心13502例0 ～ 17周岁体检儿童的血清25-(OH)D结果,计算各年龄组维生素D过量、中毒的情况.对比VD过量[(25-(OH)D水平250 ～ 375.0 nmol/L]与中毒组[(25-(OH)D水平≥375.0nmol/L)血清Ca、IP、ALP、钙磷乘积(CPP),并做血清Ca、CPP、VD的相关分析.结果 13502例儿童中,过量和中毒分别为34例(0.25％)、35例(0.26％),血清Ca最大值2.78 mmol/L,仅3例Ca＞2.74 mmol/L,两组间Ca、IP、ALP、CPP比较差异无统计学意义(P＞0.05),血清Ca与CPP的Pearson相关分析:相关系数为0.762,P=0.000,血清Ca与CPP呈正的直线相关,血清Ca与VD、CPP与VD无明显直线相关.过量组与中毒组的总69例和CPP超过60的36例以CPP分别做秩和检验,Marm-Whitney U分别等于427.500、88.000,P值分别等于0.044、0.025,差异有统计学意义.结论 这一组VD过量病例血清Ca无明显升高,随着VD水平的增高,CPP超过60的病例明显增加,提示有潜在软组织钙化的可能.     

儿童口服钙剂及其合理应用分析

目的:为儿童钙剂的合理选择提供依据。方法:参阅相关文献,对８种儿童常用口服钙剂从主要成分、常用剂量、钙元素含量等方面进行了分析、比较。结果:在普通饮食条件下,儿童应每天再从钙剂中补充２００~３００ｍｇ,基本能达到中国营养学会的每日摄钙推荐量。碳酸钙含钙元素量为 ４０%,葡萄糖酸钙含钙元素量为 ８．９%。按照常用剂量,凯思立Ｄ的日服用钙元素量最高,为５００ｍｇ/ｄ。结论:应根据儿童年龄大小和机体状况选择合适的剂型和剂量,补钙量应按钙元素含量来折算。２岁以上儿童推荐凯思立Ｄ和钙尔奇Ｄ。     

维生素D对子痫前期的影响及作用机制的研究进展

子痫前期是一种妊娠期特有的高血压性疾病,可导致母体、胎儿严重并发症.其发病机制尚未阐明.有大量研究显示维生素D缺乏与子痫前期的发生密切相关,但观点尚未统一.笔者就目前关于维生素D与子痫前期的发生及作用机制进行综述.拟通过对不同观点的归纳整理,对维生素D在子痫前期发生发展中的作用有一个更加全面的认识,有助于理解子痫前期发病机制.     

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.     

Prevalence of vitamin D inadequacy in patients attending a metabolic bone clinic in Medway

ABSTRACT

Background: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture have low levels of serum vitamin D.

Objectives:?To investigate the prevalence of vitamin D inadequacy in Medway, Kent in patients attending a metabolic bone clinic and in patients with fragility fractures and to compare levels with data previously presented from Glasgow.

Research design and methods:?Retrospective patient records audit of patients attending the metabolic bone clinic from 1998 to 2005.

Results:?There were data for 870 patients, 77.5% of the patients were women (n = 674) and 48.2% (n = 420) of patients had a fragility fracture. The mean age was 61.6 years (SD = 14.12), 56.4% were aged 60 years or over and 17.7% were aged 75 years or over. The mean vitamin D level was 47.7?nmol/L (19.1?ng/mL), SD = 25.8 (10.3). Of the patients 88.7% had a vitamin D level < 80?nmol/L, 81.4% < 70?nmol/L and 59.1% < 50?nmol/L.

Of the 420 patients with fragility fracture, 78.1% were women and the mean age was 66.6 years (SD = 12.22). The mean vitamin D level was 45.3?nmol/L (18.1?ng/mL), SD = 25.8 (10.3). In patients not receiving supplementation (n = 222) the mean vitamin D level was 40.5?nmol/L (16.2?ng/mL), SD = 20.9 (8.4) and 95.9% of patients had a vitamin D level < 80?nmol/L, 89.6% < 70?nmol/L and 71.2% < 50?nmol/L.

In order to compare data from Medway with previously published data from Glasgow, a subset of 198 patients with fragility fracture, aged over 50 years, attending the metabolic bone clinic and not receiving supplementation with calcium and/or vitamin D was analysed. There were 76.6% women and the mean age was 68.6 years (SD = 9.1). The mean vitamin D level was 40.0?nmol/L (16.0?ng/mL), SD = 21.5 (8.6). Of these patients 96.4% had a vitamin D level < 80?nmol/L,89.7% < 70?nmol/L and 73.2% < 50?nmol/L.

Data on the month of vitamin D assessment were available for 499 patients. The mean vitamin D in the summer (April–September) months (n = 217) was significantly higher than in the winter (October–March) months (n = 281): 53.2?nmol/L (SD = 29.4) versus 47.3 (SD = 24.9), p = 0.02.

Parathyroid hormone (PTH) levels were available for 289 patients. Mean vitamin D levels in the 47 patients with PTH levels above the reference range were significantly lower than vitamin D levels in the 238 patients within the reference range for PTH: mean 31.1?nmol/L, SD = 21.1 versus mean 46.5?nmol/L, SD = 24.8 (?p = 0.000092). Four patients had PTH levels below the reference range.

Conclusions:?The prevalence of vitamin D inadequacy is high in patients attending a metabolic bone clinic, in particular in those patients with fragility fractures. The prevalence of inadequacy is comparable with that seen in Glasgow.     

Using gas chromatography and mass spectrometry to determine 25-hydroxyvitamin D levels for clinical assessment of vitamin D deficiency

Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out with plasma specimens. The limit of quantitation of TMS-GC-MS method is 1.5 ppb with good linear correlation. Furthermore, the dietary intake and nutritional status of vegetarian and non-vegetarians in Taiwan were assessed by our validated method. As a result, this vitamin D nutrition survey demonstrates that most Taiwanese people have insufficient vitamin D. Due to dietary habits; the male vegans may have the highest risk of vitamin D deficiency.