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.     

Optimal vitamin D status for the prevention and treatment of osteoporosis

Vitamin D(3) (cholecalciferol) sufficiency is essential for maximising bone health. Vitamin D enhances intestinal absorption of calcium and phosphorus. The major source of vitamin D for both children and adults is exposure of the skin to sunlight. Season, latitude, skin pigmentation, sunscreen use, clothing and aging can dramatically influence the synthesis of vitamin D in the skin. Very few foods naturally contain vitamin D or are fortified with vitamin D. Serum 25-hydroxyvitamin D [25(OH)D; calcifediol] is the best measure of vitamin D status. Vitamin D deficiency [as defined by a serum 25(OH)D level of <50 nmol/L (<20 ng/mL)] is pandemic. This deficiency is very prevalent in osteoporotic patients. Vitamin D deficiency causes osteopenia, osteoporosis and osteomalacia, increasing the risk of fracture. Unlike osteoporosis, which is a painless disease, osteomalacia causes aching bone pain that is often misdiagnosed as fibromyalgia or chronic pain syndrome or is simply dismissed as depression. Vitamin D deficiency causes muscle weakness, increasing the risk of falls and fractures, and should be aggressively treated with pharmacological doses of vitamin D. Vitamin D sufficiency can be sustained by sensible sun exposure or ingesting at least 800-1000 IU of vitamin D(3) daily. Patients being treated for osteoporosis should be adequately supplemented with calcium and vitamin D to maximise the benefit of treatment.     

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.     

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.     

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 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.     

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

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 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.     

Calcidiol [25(OH)D3]: from diagnostic marker to therapeutical agent

Abstract

Objective:

Osteoporosis is a skeletal disorder characterized by diminished bone strength, which results in an increased risk of fracture. Currently, osteoporosis is a public health priority due to the large number of individuals affected and the detrimental effect on quality of life. Primary osteoporosis, the most common form, usually results from age-related reduction in bone mineral strength. Over time, the individual’s capacity to build bone is impaired, as the synthesis of vitamin D, the hormone responsible for calcium absorption, tends to decline. As serum calcium levels decrease, metabolic control serves to increase the removal of calcium from the skeleton to make up for the deficit. The synthesis of the ‘hormone’ vitamin D and its control therefore become central to intervention in involutional osteoporosis syndromes. In humans, plain vitamin D (cholecalciferol), also called parental or native vitamin D, is photosynthesized in the skin and then hydroxylated in the liver into the vitamin D analog calcidiol [25(OH)D3], which is hydroxylated again in the kidney into the vitamin D analog calcitriol [1,25(OH)2D3]. The advantage of administering vitamin D analogs is that the pro-drug calcidiol avoids the effect of declines in hepatic function, while calcitriol avoids the effect of declines in hepatic and kidney function. A strategy to enhance [25(OH)D3] levels to the optimal threshold of vitamin D is supplementation with the calcidiol metabolite itself. The goal of this paper is to review published studies on the efficacy of the calcidiol metabolite in increasing 25(OH)D3 serum levels and improving skeletal health parameters in humans.     

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.     

Osteoporosis: a new challenge in cystic fibrosis

The increased life expectancy of patients with cystic fibrosis (CF) may lead to medical complications such as osteoporosis. Based on data collected through a MEDLINE search (1985-May 1999) and review of references for additional relevant articles, nutrition status, weight, and disease severity are factors most highly correlated with osteopenia. Links also were noted with calcium and vitamin D intake, hypogonadism, chronic inflammation, and age, but findings in these areas are not consistent from one report to the next. Increased fracture rates and kyphosis are consequences of osteoporosis. Simple measures such as compliance with recommended nutrition guidelines and restrictions in corticosteroid therapy could be considered first-line management options. Further studies must be conducted to clarify factors involved in the etiology of osteoporosis in patients with CF and to identify the best treatment and prevention methods.     

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.     

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.     

The high prevalence of inadequate serum vitamin D levels and implications for bone health

BACKGROUND: Inadequate serum vitamin D is associated with secondary hyperparathyroidism, increased bone turnover, and bone loss, which increased fracture risk. Osteomalacia has also been observed in severe cases. Indeed, vitamin D and calcium are essential components of management strategies for the prevention and treatment of osteoporosis. Despite this, many people currently do not have adequate vitamin D levels. This problem has been documented in many studies around the world, regardless of age, health status, or latitude, and is especially common among older adults, who are also likely to have osteoporosis. Factors that contribute to low vitamin D include low exposure to sunlight, decreased synthesis in skin and reduced intestinal absorption related to aging, and limited dietary sources. Supplementation is the most effective means of correcting poor vitamin D nutrition. However, few patients with osteoporosis currently take sufficient vitamin D supplements. SCOPE: This review article discusses the role of vitamin D in osteoporosis and skeletal health, and summarizes what is known about the high prevalence of inadequate serum vitamin D and recommendations for supplementation. CONCLUSION: Greater awareness of the importance of vitamin D for skeletal health and more aggressive supplementation efforts are urgently needed to address this important public health problem.     

Alendronate with and without cholecalciferol for osteoporosis: results of a 15-week randomized controlled trial

OBJECTIVE: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70 mg and cholecalciferol 70 microg (2800 IU) (ALN + D) versus alendronate 70 mg alone (ALN). METHODS: This 15-week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 25OHD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (n = 35) and postmenopausal women (n = 682) with osteoporosis and 25OHD >or= 9 ng/mL were randomized to ALN + D (n = 360) or ALN (n = 357). MAIN OUTCOME MEASURES: Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N-telopeptide collagen cross-links (NTX). RESULTS: Serum 25OHD declined from 22.2 to 18.6 ng/mL with ALN (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15 ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [p < 0.001]), and the RR of 25OHD < 9 ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p < 0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX). CONCLUSION: In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.     

Relative contributions of diet and sunlight to vitamin D state in the elderly.

In winter the vitamin D state of elderly people may reach levels associated with osteomalacia, although the disease may not be clinically apparent. A statistical correlation was observed in a group of elderly subjects during the winter between dietary vitamin D intake and vitamin D state, but the intake was generally too low to make a biologically important contribution to maintaining vitamin D concentrations. Ultraviolet light (UVL) is the primary determinant of vitamin D state in summer and winter, in winter owing to the pools of vitamin D built up during the previous summer. Plasma concentrations of 25-hydroxy vitamin D (25-OHD) in winter of 15.0-22.5 nmol/l (6-9 ng/ml) require that the concentration in the previous summer was over 40 nmol/l (16 ng/ml). To maintain plasma concentrations in the elderly above those associated with osteomalacia a mean dietary vitamin D intake of over 5 microgram/day is required. A more physiological approach, however, would be to increase exposure to UVL.     

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.     

Vitamin D status in relation to age,bone mineral density of the spine and femur in obese Saudi females – A hospital-based study

The aim of the present study was to evaluate the association between Bone mineral density in lumber spine and femoral neck with serum total levels of vitamin D, sun exposure and Consumption of vitamin D Supplement in obese Saudi females aged between 30 and 54?years old. Recent attention to the high prevalence of osteoporosis and its association with low vitamin D levels in adults has raised the importance of vitamin D evaluation. A low level of vitamin D is considered to be one of the most important risk factors for osteoporosis. In this study; 120 obese Saudi females with no diagnosed chronic diseases attending the Outpatient clinic at king Khalid University hospital in Riyadh. Saudi Arabia, recruited randomly in period of 12?months. In this study, Serum levels of total Vitamin D were considered to be severe deficient if it was lower than 25?ng/mL, mild to moderate deficient if it was between 25 and 60?ng/mL and optimum level if it was 61–200?ng/mL. The results showed that; sun exposure was significantly affect and Correlate with serum level of Vitamin D in the subjects. In addition, daily consumption of Vitamin D supplement was significantly affect and Correlate with serum level of Vitamin D in the subjects of this study. Moreover, the results showed that; 50% of the age group (40–49?years old) having severe deficiency of Vitamin D. While, 50% of the age group (50–59?years old) having optimal level of Vitamin D. And these results mean that age is not Correlated with vitamin D deficiency in subjects of this study.     

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.     

Review article: Osteoporosis and inflammatory bowel disease

Studies using dual-energy X-ray absorptiometry have suggested a high prevalence of osteoporosis in inflammatory bowel disease. However, population-based data on fracture incidence suggest only a small increased risk of fracture amongst patients with inflammatory bowel disease compared with the general population. Therefore, it would be helpful to identify patients with inflammatory bowel disease at particularly high risk for fracture so that these risks might be modified or interventions might be undertaken. The data on calcium intake as a predictor of bone mineral density are conflicting. Although there are data suggesting that a one-time survey to determine current calcium intake will not help to predict bone mineral density in inflammatory bowel disease, persistently reduced calcium intake does appear to lead to lower bone mineral density. In the general population, body mass is strongly correlated with bone mineral density, which also appears to be true in Crohn's disease. Hence, subjects with inflammatory bowel disease and considerable weight loss, or who are obviously malnourished, could be considered for bone mineral density testing, and the finding of a low bone mineral density would suggest the need for more aggressive nutritional support. Although vitamin D is undoubtedly important in bone health, vitamin D intake and serum vitamin D levels do not correlate well with bone mineral density. Sex hormone deficiency can also adversely affect bone health, although a well-developed strategy for sex hormone measurements in patients with inflammatory bowel disease remains to be established. Ultimately, the determination of genetic mutations that accurately predict fracture susceptibility may be the best hope for developing a simplified strategy for managing bone health in inflammatory bowel disease. The therapy of osteoporosis in inflammatory bowel disease has been adapted from other osteoporosis settings, such as post-menopausal or corticosteroid-induced osteoporosis. To date, there remains no therapy proven to be efficacious in inflammatory bowel disease-related osteoporosis; however, calcium and vitamin D supplementation and bisphosphonates have their roles.