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

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.     

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.     

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 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.     

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.     

Prevalence of vitamin D inadequacy in a minimal trauma fracture population

ABSTRACT

Objective: The purpose of this analysis was to report the prevalence of vitamin D inadequacy in a population of adults with minimal trauma fractures.

Research Design and Methods: 82 adults (ages 52–97 with 63% age 80+) consecutively hospitalized with hip and extremity fractures between August 2001 and January 2002 were recruited from two St. Paul, MN hospitals. Patients came from independent living and assisted living facilities. Demographics, medical history and vitamin D supplementation were obtained by the medical record and self-report. Blood specimens were collected during hospitalization within 48 hours of admission. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were assessed using Diasorin 25-hydroxyvitamin D radioimmunoassay kit (RIA) at Mayo Clinic, Rochester, MN. Results were available for 78 patients and are included in the current analysis.

Results: Patients were 99% Caucasian, 63% ≥ 80 years and 78% female. 97% were admitted due to hip fracture. On admission, 50% reported using at least 400?IU per day of vitamin D through supplements (including multivitamins) and 13% of all patients were taking osteoporosis medication (3 estrogen, 5 alendronate, 1 etidronate, 1 raloxifene). The mean 25(OH)D concentration was 14.2 (SD 6.6) with a range of 5–39?ng/mL (8–38?ng/mL wintertime vales in Rochester, MN). All but two of the 78 patients (97.4%) had 25(OH)D concentrations < 30?ng/mL and the majority (81%) of the patients had 25(OH)D concentrations < 20?ng/mL, including 21% < 9?ng/mL. Mean 25(OH)D concentrations were not substantially different by gender, age, or osteoporosis medication use. Patients who reported vitamin D supplementation ≥ 400?IU/day had significantly greater mean 25(OH)D concentrations, albeit suboptimal, compared to those who did not (16.4 vs. 13.7?ng/mL; p = 0.002).

Conclusions: Nearly all patients in this study hospitalized for fracture had vitamin D inadequacy. Significant opportunity exists to ensure adequate and persistent vitamin D intake in a high risk fracture patient population.     

Prevalence of vitamin D inadequacy in Belfast following fragility fracture

BACKGROUND: It is well established that vitamin D levels are sub-optimal in older people and that adults with fragility fracture have low levels of serum vitamin D. OBJECTIVES: To investigate the prevalence of vitamin D inadequacy in an elderly population with fragility fractures and to compare data with previously published work from Glasgow. RESEARCH DESIGN AND METHODS: Two retrospective patient audits were carried out using records from the out-patient Osteoporosis Clinic at Musgrave Park Hospital and from in-patient hip fracture admissions at the Royal Victoria Hospital. RESULTS: There were data for 86 patients with fragility fracture from the Osteoporosis Clinic, 40.7% patients had vertebral fractures and 10.5% multiple fractures. Patients with hip fracture were excluded from the analysis. 69.8% of the patients were women. The mean age at the time of fracture was 65.3 years and 70.9% of patients were aged 60 years or over and 32.6% were aged 75 years or over. At the time of out-patient attendance, 73.3% were receiving supplementation with calcium and vitamin D. The mean vitamin D level was 52.3 nmol/L (21.0 ng/mL), SD = 23.4 (9.4). There were 83.7% of patients who had a vitamin D level < 80 nmol/L, 73.3% < 70 nmol/L and 55.8% < 50 nmol/L.There were no significant differences by patient age or sex. Data were also analysed according to supplementation status, in patients not taking supplements (n = 23) mean vitamin D level was 48.1 nmol/L (19.3 ng/mL), SD = 27.4 (11.0) compared with 53.8 nmol/L (21.6 ng/mL), SD = 21.8 (8.7) in the 63 patients taking supplements. Prevalence of inadequacy was higher in the patients not taking supplements 82.6% versus 67.1% at the 70 nmol/L threshold. There were data for 43 hip fracture patients, 95.3% of the patients were women. The mean age at the time of fracture was 78.3 years, 95.3% of patients were aged 60 years or over and 69.8% were aged 75 years or over. Data were not available on whether these patients were receiving supplementation. The mean vitamin D level was 36.1 nmol/L (14.5 ng/mL), SD = 24.8 (9.9). 90.7% of patients had a vitamin D level < 80 nmol/L, 88.4% < 70 nmol/L ( approximately 28 ng/mL) and 88.4% < 50 nmol/L ( approximately 20 ng/mL). CONCLUSIONS: The levels of vitamin D inadequacy revealed in this audit were similar to those in an earlier audit carried out in Glasgow. Thus studies at two locations in the UK confirm the high prevalence of vitamin D inadequacy, furthermore, the prevalence of inadequacy appears to be higher in those patients with a hip fracture.     

维生素D与婴幼儿哮喘的关系

维生素D是人体必需营养成分之一,婴幼儿哮喘是婴幼儿常见的呼吸系统疾病。近年来,国内外关于维生素D与婴幼儿哮喘之间关系的临床研究很多,本文就二者之间的关系展开综述,希望给临床提供一定参考。     

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。     

骨质疏松性髋部骨折患者髂骨活检及扫描电镜观察

目的　了解骨显微结构退变在骨质疏松性髋部骨折发病机制中的作用。方法　对 14例老年髋部骨折患者和 11例对照者进行了髂骨活检和扫描电镜观察。结果　老年髋部骨折患者的扫描电镜观察结果可以分为低转换和高转换两种情况。后者除骨小梁数量减少、变细等改变外 ,骨小梁结构显著退变。结论　因活跃的骨转换活动而导致的骨显微结构退变 ,是部分髋部骨折的重要原因     

婴幼儿维生素D缺乏调查及维生素D补充对血清25-羟维生素D水平的影响

目的 调查婴幼儿维生素D缺乏情况及探讨维生素D补充对血清25-羟维生素D[25-(OH)D]水平的影响.方法 378例婴幼儿按月龄分为A组(0-6个月,142例)、B组(7-12个月,168例)和C组(13-36个月,68例).其中,部分婴幼儿近3个月口服不同剂量维生素D 250 IU/d(D组,46例)、300 IU/d(E组,82例)和500 IU/d(F组,171例),79例未补充维生素D(G组).采集婴幼儿指尖血,用酶联免疫法检测血清25-(OH)D水平,计算维生素D缺乏发生率.结果 婴幼儿维生素D缺乏发生率为21.16％(80/378).B组血清25-(OH)D水平高于A、C组[(72.0±23.2)nmol/L vs.(67.0±24.8)、(55.9±12.4)nmol/L](P＜0.05),而维生素D缺乏发生率低于A、C组(13.10％ vs.21.83％、39.71％) (P＜0.05).D、E、F组血清25-(OH)D水平均高于G组[(63.6±16.9)、(69.9±20.1)、(71.5±27.8)nmol/L vs.(57.2±11.9) nmol/L] (P＜0.05),而维生素D缺乏发生率均低于G组[26.09％、21.95％、13.45％ vs.34.18％](P＜0.05);D、E组维生素D缺乏发生率高于F组(P＜0.05).结论 婴幼儿维生素D普遍缺乏,建议补充维生素D500 IU/d,0-6个月和13-36个月的婴幼儿维生素D缺乏情况应予重视.     

Vitamin D inadequacy in postmenopausal women in Eastern Asia

ABSTRACT

Objective: To review data on the prevalence of vitamin D inadequacy and its causes in postmenopausal women in Eastern Asia.

Research design and method: Data were obtained from the published biomedical literature as well as abstracts and posters presented at scientific meetings. Using MEDLINE, EMBASE and BIOSIS databases (to July 2007), epidemiological studies were identified using the search terms: ‘human’, ‘vitamin D’, ‘vitamin D deficiency’, ‘vitamin D inadequacy’, ‘vitamin D insufficiency’ and ‘hypovitaminosis D’, ‘osteomalacia’ and ‘osteoporosis’. Additional references were also identified from the bibliographies of published articles.

Results: The prevalence of vitamin D inadequacy in studies of postmenopausal women (ambulatory or with osteoporosis or related musculoskeletal disorders) in Eastern Asia ranged from 0 to 92%, depending on the cut-off level of serum 25-hydroxycholecalciferol [25(OH)D] that was applied (range ≤6–35?ng/mL [≤15–87?nmol/L]). One large international study found that 71% of postmenopausal women with osteoporosis in Eastern Asia had vitamin D inadequacy, defined as serum levels of 25(OH)D <30?ng/mL (75 nmol/L). Prevalence rates using this cut-off level were 47% in Thailand, 49% in Malaysia, 90% in Japan and 92% in South Korea. High prevalences of vitamin D inadequacy were evident in two studies using a lower 25(OH)D level cut-off value of <12?ng/mL(30?nmol/L) – 21% in China and 57% in South Korea. Dietary deficiency and inadequate exposure or reactivity to sunlight (due to lifestyle choices, cultural customs and/or aging) were identified as important risk factors for vitamin D inadequacy.

Conclusions: Non-uniform, epidemiological studies indicate a high prevalence of vitamin D inadequacy in postmenopausal women in Eastern Asia. Recommended remedial approaches are education campaigns and broad-based provision of vitamin D supplementation.     

Prevalence of vitamin D inadequacy in a minimal trauma fracture population

OBJECTIVE: The purpose of this analysis was to report the prevalence of vitamin D inadequacy in a population of adults with minimal trauma fractures. RESEARCH DESIGN AND METHODS: 82 adults (ages 52-97 with 63% age 80+) consecutively hospitalized with hip and extremity fractures between August 2001 and January 2002 were recruited from two St. Paul, MN hospitals. Patients came from independent living and assisted living facilities. Demographics, medical history and vitamin D supplementation were obtained by the medical record and self-report. Blood specimens were collected during hospitalization within 48 hours of admission. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were assessed using Diasorin 25-hydroxyvitamin D radioimmunoassay kit (RIA) at Mayo Clinic, Rochester, MN. Results were available for 78 patients and are included in the current analysis. RESULTS: Patients were 99% Caucasian, 63% >/=80 years and 78% female. 97% were admitted due to hip fracture. On admission, 50% reported using at least 400 IU per day of vitamin D through supplements (including multivitamins) and 13% of all patients were taking osteoporosis medication (3 estrogen, 5 alendronate, 1 etidronate, 1 raloxifene). The mean 25(OH)D concentration was 14.2 (SD 6.6) with a range of 5-39 ng/mL (8-38 ng/mL wintertime vales in Rochester, MN). All but two of the 78 patients (97.4%) had 25(OH)D concentrations < 30 ng/mL and the majority (81%) of the patients had 25(OH)D concentrations < 20 ng/mL, including 21% < 9 ng/mL. Mean 25(OH)D concentrations were not substantially different by gender, age, or osteoporosis medication use. Patients who reported vitamin D supplementation >/= 400 IU/day had significantly greater mean 25(OH)D concentrations, albeit suboptimal, compared to those who did not (16.4 vs. 13.7 ng/mL; p = 0.002). CONCLUSIONS: Nearly all patients in this study hospitalized for fracture had vitamin D inadequacy. Significant opportunity exists to ensure adequate and persistent vitamin D intake in a high risk fracture patient population.     

Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies

ABSTRACT

Objective: The marketed doses of ibandronate, 150?mg once-monthly oral and 3?mg quarterly intravenous (IV) injection, produce greater increases in lumbar spine bone mineral density than treatment with the 2.5?mg oral daily dose. This meta-analysis assessed whether these doses also reduce fracture risk relative to placebo.

Study design and methods: Individual patient data from the intent-to-treat populations of the BONE, IV fracture prevention, MOBILE, and DIVA studies were grouped into three dose levels based on annual cumulative exposure (ACE), defined as the annual dose (mg) × bioavailability (0.6%, oral; 100%, IV) or placebo. Six key non-vertebral fractures (NVFs) (clavicle, humerus, wrist, pelvis, hip, and leg), all NVFs, and all clinical fractures were examined.

Results: This meta-analysis included 8710 patients. Cox proportional-hazards models estimated the adjusted relative risk (RR) for fracture with ibandronate versus placebo, and time to fracture was compared using log-rank tests. The high-dose group (ACE?≥?10.8?mg) showed significant reductions in the adjusted RR of key NVFs (34.4%, p?=?0.032), all NVFs (29.9%, p?=?0.041), and clinical fractures (28.8%, p?=?0.010) relative to placebo. The high-dose group also had significantly longer time to fracture versus placebo for key NVFs (p?=?0.031), all NVFs (p?=?0.025), and clinical fractures (p?=?0.002). Study limitations included: not all studies were placebo-controlled; a limited number of baseline characteristics were available for multivariate analyses.

Conclusion: Ibandronate at dose levels of ACE?≥?10.8?mg, which includes the marketed 150?mg once-monthly oral and 3?mg quarterly IV injection regimens, may provide significant non-vertebral and clinical 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.     

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

BACKGROUND: It is well established that vitamin D levels are suboptimal 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.     

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.