Glucocorticoids Vitamin D
Do Glucocorticosteroids Alter Vitamin D Status? A Systematic Review with Meta-Analyses of Observational Studies
Zoe E. Davidson, 1Monash University, Southern Clinical School of Medicine, Department of Nutrition and Dietetics, Clayton, Victoria, Australia 3168 *Address all correspondence and requests for reprints to: Z. E. Davidson, Monash University, Department of Nutrition and Dietetics, Southern Clinical School of Medicine, Monash Medical Centre, Level 5, Block E, 246 Clayton Road, Clayton, Victoria, Australia 3168. Search for other works by this author on: 1Monash University, Southern Clinical School of Medicine, Department of Nutrition and Dietetics, Clayton, Victoria, Australia 3168 Search for other works by this author on: 1Monash University, Southern Clinical School of Medicine, Department of Nutrition and Dietetics, Clayton, Victoria, Australia 3168 Search for other works by this author on:
Received:
05 October 2011
Accepted:
01 December 2011
Context:
Vitamin D supplementation is an important adjunct therapy for the prevention and management of glucocorticoid-induced osteoporosis. There has been little exploration of the relationship between glucocorticosteroid (GCS) use and serum 25-hydroxyvitamin D [25(OH)D].
Objective:
The aim of this study was to systematically explore how serum 25(OH)D is altered in adult patients receiving GCS.
Data Sources:
We reviewed Medline and Cinahl databases between January 1970 and August 2011.
Study Selection:
Experimental studies were included where 25(OH)D was measured in patients more than 18 yr of age receiving GCS therapy. Studies were excluded if patients received at least 400 IU/d (10 ÎĽg/d) vitamin D, if GCS treatment was less than 2-wk duration, if more than 50% of the study population received GCS for renal or hepatic disease or after transplant, or if the study population included patients with Cushing's syndrome. A consensus method was used to classify studies. Of identified studies, 3% met the selection criteria.
Data Extraction:
Data were extracted by a single author. Study quality was assessed using criteria developed by the American Dietetic Association.
Data Synthesis:
The weighted mean 25(OH)D (by sample size or sd) was 22.4 [95% confidence interval (CI), 19.4, 25.3] ng/ml and 21.0 (95% CI, 13.5, 28.5) ng/ml, respectively. Random effects meta-analysis was used to compare serum 25(OH)D in patients treated with GCS compared to steroid-naive controls (either healthy or with active disease) and in patients before and after GCS administration. Serum 25(OH)D in GCS users was on average −0.5 (95% CI, −1.0, −0.1) ng/ml lower than in healthy controls (P = 0.03; I2 = 56.4%). Serum 25(OH)D did not differ between GCS users and disease controls [standardized mean difference = 0.0 (95% CI, −0.2, 0.3) ng/ml; P = 0.793; I2 = 16.2%].
Conclusion:
The suboptimal concentrations of serum 25(OH)D found in adults receiving GCS are inadequate for prevention and management of glucocorticoid-induced osteoporosis. Recommendations for vitamin D supplementation should be adjusted accordingly.
Glucocorticoidsteroids (GCS) are prescribed as a primary management strategy in a large range of conditions, including inflammatory bowel disease, rheumatoid arthritis, autoimmune diseases, and Duchenne muscular dystrophy. Although GCS are efficacious in managing these inflammatory conditions, their use can be accompanied by substantial side effects. Important among these is glucocorticoid-induced osteoporosis (GIO), the most widespread form of secondary osteoporosis (1). GIO contributes to fractures in as many as 30–50% of adults prescribed GCS (2), even when they receive 2.5- to 7.5-mg prednisone equivalents per day (3).
Sustained use of GCS increases bone loss by reducing intestinal calcium absorption and increasing renal excretion, so that the ensuing negative calcium balance leads to increased bone resorption (4). To combat this, vitamin D supplementation has been explored as a potential adjunct therapy because vitamin D regulates calcium homeostasis by increasing intestinal calcium absorption and reabsorption from the kidneys (5). The formation of the biologically active form of vitamin D requires two sequential hydroxylation steps, one in the liver to produce calcidiol [25(OH)D], and the second in the kidney (under the influence of PTH) to produce calcitriol (1,25-dihydroxyvitamin D3) (6). Calcidiol remains the best serum measure of vitamin D status and is the form in which oral doses are provided (7, 8).
For the purpose of this review, vitamin D deficiency is defined as serum 25(OH)D below 20 ng/ml (8). At 25(OH)D concentrations of 10–20 ng/ml (25–50 nmol/liter), PTH is distinctly elevated, intestinal calcium absorption is reduced, and deleterious effects on bone mineralization are evident (9). Even when serum 25(OH)D falls below 24–30 ng/ml (60–75 nmol/liter), muscle and immune function can be compromised (10). Although levels of required vitamin D supplementation remain the subject of debate, one study has indicated that a daily dose of 4000 IU (100 ÎĽg) of vitamin D for 2 months was required to raise serum 25(OH)D above 24 ng/ml (60 nmol/liter) in 27 of 28 otherwise healthy adults with basal 25(OH)D at 15.2 ± 5.4 ng/ml (37.9 ± 13.4 nmol/liter) (11).
Several systematic reviews indicate the efficacy of vitamin D plus calcium supplementation in maintaining bone mineral density (12, 13) and reducing vertebral fracture risk (14) in patients treated with GCS. What level of vitamin D supplementation is then optimal in these patients? The 2010 recommendations for the prevention and treatment of GIO from the American College of Rheumatology (15) advise supplementation with 800-1000 IU/d (20–25 ÎĽg/d) 25(OH)D, although it is conceded that more may be necessary if GCS adversely affects vitamin D absorption (15). Recommendations from The Endocrine Society (8) suggest higher levels of supplementation, proposing that patients using GCS require two to three times more vitamin D than healthy people of the same age. For a 30-yr-old individual, this equates to a dose of 3000–6000 IU/d (75–150 ÎĽg/d) 25(OH)D. Conversely, the Royal College of Physicians of London recommends vitamin D supplementation only in cases of vitamin D deficiency (16).
Although it is evident that vitamin D supplementation is beneficial in the prevention and treatment of GIO, the extent to which GCS compromises vitamin D status remains unclear. This is a critical gap in knowledge. Historically, prednisone was thought to decrease the plasma half-life of vitamin D (17), although this half-life is most likely to be that of 25(OH)D. The long-term effects of chronic steroid use on plasma 25(OH)D levels are uncertain. Some authors suggest that 25(OH)D levels remain normal (18–20), and others report reduced levels long term (21, 22). Importantly, because vitamin D deficiency is itself a risk factor for osteopenia, osteoporosis, and increased fracture risk (23), vitamin D insufficiency or deficiency may compound the effects of GIO and attenuate the effectiveness of a standard vitamin D supplementation at 800-1000 IU/d (20–25 ÎĽg/d) because achievement of optimal plasma levels of 25(OH)D is known to be highly dependent on the initial starting value (24).
The primary objective of this systematic review and meta-analysis was to determine serum 25(OH)D concentrations in patients treated with GCS; specifically we wished to test the hypothesis that serum 25(OH)D is decreased in patients treated with GCS compared with those not receiving GCS. This question has been investigated using three methods: calculation of the weighted mean serum 25(OH)D concentration in patients treated with GCS; comparison of serum 25(OH)D in patients treated with GCS compared with controls who are steroid naive and are either healthy or who have active disease; and comparison of serum 25(OH)D before and after GCS administration. Data have been drawn from all experimental designs, though primarily from cross sectional measures of 25(OH)D. To our knowledge, this is the first systematic review to explore the relationship between serum 25(OH)D and GCS use. Understanding this relationship will inform the evidence base on which recommendations for vitamin D supplementation can be tailored specifically for patients prescribed GCS.
Materials and Methods
The search strategy was determined by two investigators (Z.E.D. and H.T.) and conducted by one (Z.E.D.). The systematic review was originally conducted in May 2010 and was updated in August 2011 through a search of two databases (Medline via Ovid and Cinahl) using the following keywords: prednisolone, glucocorticoids, adrenal cortex hormones, vitamin D, vitamin D deficiency, vitamin D insufficiency. In addition, the Medline search incorporated two terms: hydroxycholecalciferols and dihydroxycholecalciferols. In the Cinahl search, added terms were: 25-hydroxyvitamin D, cholecalciferols, and calcitriol. All search terms were "exploded." Each search was limited to human studies published in English between January 1970 and August 2011. No attempt was made to access unpublished communications. All recovered abstracts were reviewed (by Z.E.D.) and where eligibility was unclear, the full article was also reviewed by H.T. Articles were retrieved where studies measured 25(OH)D in any population older than 18 yr treated with GCS. All experimental study designs were included, but case studies, commentaries, narrative reviews, conference abstracts, and editorials were excluded. Studies were coded as included or excluded. Reasons for exclusion were: not a study, not a relevant population, not a relevant outcome, duplicate, or unable to be retrieved. To be eligible for data extraction, retrieved studies were reexamined against further criteria (Table 1). Retrieved studies were also hand-searched for further references meeting inclusion criteria for this review. Contact with study authors was found not to be required.
Table 1.
Reasons for exclusion of studies in patients treated with GCS
| Excluded |
| Vitamin D supplementation ≥400 IU/d (10 ÎĽg/d) |
| GCS treatment <2-wk duration |
| Duration of GCS treatment unclear |
| Serum 25(OH)D not measured |
| >50% of study population on GCS for renal or hepatic disease |
| >50% of study population on GCS after transplant |
| Study population includes a patient with Cushing's syndrome |
| Vitamin D supplementation study without a measure of 25(OH)D at baseline a |
| 25(OH)D in users vs. nonusers of GCS not clearly defined |
| Treatment status with GCS unclear in some subjects |
| Excluded |
| Vitamin D supplementation ≥400 IU/d (10 ÎĽg/d) |
| GCS treatment <2-wk duration |
| Duration of GCS treatment unclear |
| Serum 25(OH)D not measured |
| >50% of study population on GCS for renal or hepatic disease |
| >50% of study population on GCS after transplant |
| Study population includes a patient with Cushing's syndrome |
| Vitamin D supplementation study without a measure of 25(OH)D at baseline a |
| 25(OH)D in users vs. nonusers of GCS not clearly defined |
| Treatment status with GCS unclear in some subjects |
a Except where patients commenced GCS and vitamin D supplementation at the same time and there was no placebo arm (GCS alone).
Table 1.
Reasons for exclusion of studies in patients treated with GCS
| Excluded |
| Vitamin D supplementation ≥400 IU/d (10 ÎĽg/d) |
| GCS treatment <2-wk duration |
| Duration of GCS treatment unclear |
| Serum 25(OH)D not measured |
| >50% of study population on GCS for renal or hepatic disease |
| >50% of study population on GCS after transplant |
| Study population includes a patient with Cushing's syndrome |
| Vitamin D supplementation study without a measure of 25(OH)D at baseline a |
| 25(OH)D in users vs. nonusers of GCS not clearly defined |
| Treatment status with GCS unclear in some subjects |
| Excluded |
| Vitamin D supplementation ≥400 IU/d (10 ÎĽg/d) |
| GCS treatment <2-wk duration |
| Duration of GCS treatment unclear |
| Serum 25(OH)D not measured |
| >50% of study population on GCS for renal or hepatic disease |
| >50% of study population on GCS after transplant |
| Study population includes a patient with Cushing's syndrome |
| Vitamin D supplementation study without a measure of 25(OH)D at baseline a |
| 25(OH)D in users vs. nonusers of GCS not clearly defined |
| Treatment status with GCS unclear in some subjects |
a Except where patients commenced GCS and vitamin D supplementation at the same time and there was no placebo arm (GCS alone).
Review of all included studies (by Z.E.D.) led to the extraction of the following information: affiliation and source of funds, study design, location, sample size, population characteristics, potential confounding variables (age, gender, ethnicity, vitamin D supplementation, sun exposure, cumulative GCS dose, daily GCS dose), type of 25(OH)D assay, and mean serum 25(OH)D. Any studies providing insufficient information for the meta-analysis were now excluded; at a minimum, a sample size and a mean serum 25(OH)D level were required.
Study quality was assessed as positive, neutral, or negative according to criteria developed by the American Dietetic Association (25). Levels of evidence were assigned according to an accepted hierarchy (26). Whenever the measure of 25(OH)D taken came from a single point within an intervention or cohort study (e.g. baseline measure), the level of evidence was considered equivalent to a cross-sectional study. Study quality and level of evidence were not considered when assessing eligibility for inclusion.
Statistical methods
Analyses were undertaken using STATA (version 11, 2009; StataCorp, College Station TX). The relationship between GCS treatment and serum 25(OH)D was explored by meta-analysis. Three key elements were examined: the weighted mean 25(OH)D concentrations, comparison of 25(OH)D concentrations in GCS users and nonusers, and comparison of 25(OH)D before and after GCS administration. All measures of 25(OH)D have been reported as nanograms per milliliter.
Weighted mean 25(OH)D
The weighted mean was calculated first in accordance with sample size (27) and second in relation to the sd with consideration of random effects principles (27). Studies were included in these analyses if they provided the mean serum 25(OH)D concentration plus either the sample size or a sd or sem, respectively.
Comparison of 25(OH)D between GCS users and nonusers
Studies allowing comparison of 25(OH)D concentrations between GCS users and nonusers reported mean ± sd (or sem) serum 25(OH)D concentrations for a cohort of GCS users and a cohort of steroid-naive controls (either healthy or with a disease). Where 25(OH)D was reported for several GCS-treated groups vs. one control group, the measure with the least variation was used in analyses. Effect sizes were calculated using Cohen's d (28). A negative d value indicates that serum 25(OH)D is decreased in GCS users compared with nonusers. Effect sizes are taken as small, d = 0.2; medium, d = 0.5; and large, d = 0.8 (28).
The STATA "metan" command (29) was used to calculate overall weighted mean difference in serum 25(OH)D between GCS users and all controls (healthy and diseased), between GCS users and healthy controls, and between GCS users and controls with active disease. A random effects model was also used whereby the standardized mean difference (SMD) was used in place of mean 25(OH)D. Heterogeneity was examined both qualitatively and quantitatively using the I2 statistic: low heterogeneity is defined as below 25%, medium as below 50%, and high as below 75% (30).
Comparison of 25(OH)D before and after GCS administration
Studies were included for comparison of 25(OH)D before and after GCS administration if they reported 25(OH)D and sd or sem in a group of subjects before commencing GSC and after at least 1 month of treatment. Studies were excluded if GCS administration was accompanied by supplementation with vitamin D. Again, Cohen's d was used to estimate effect size and the overall SMD was calculated.
Results
The process of study selection for the meta-analyses is illustrated in Supplemental Fig. 1 (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). From the search, 1309 studies were received for classification. Of these, 171 studies, including 10 studies identified via a hand search, were retrieved—of which 38 were found eligible for data extraction. During data extraction, 13 additional studies were excluded because they provided insufficient data points for inclusion in any meta-analyses. Of the 25 included studies, 12 were cross-sectional studies, two were cohort studies, six studies had either a single arm intervention or were a nonrandomized control trial, and five were randomized control trials. One additional study became available after the search was completed. This could not be included in the meta-analysis due to the lack of mean values for vitamin D in steroid-treated patients (31).
The studies included in the meta-analyses are summarized in Supplemental Tables 1, 2, and 3. Most (92%) were assessed as of neutral quality only; one paper was assessed as positive quality (32) and one as negative quality (33). Participants included patients treated with GCS for inflammatory bowel disease, sarcoidosis, rheumatoid arthritis and other rheumatic disorders, chronic obstructive pulmonary disorder, asthma, connective tissue disorders, and systemic lupus erythematosis. Thirteen of the 25 included studies were conducted in the United States, others were from Europe (n = 10), New Zealand (n = 1), and Canada (n = 1). Participants were aged 23–69 yr and 0–100% male, and they were given 5–150 mg/d GCS. Serum 25(OH)D was generally determined by competitive protein binding assay or RIA.
Weighted mean serum 25(OH)D
A total of 25 studies with 867 participants allowed the determination of a mean 25(OH)D weighed by sample size as 22.4 (95% CI, 19.4, 25.3) ng/ml, whereas 23 studies with 640 participants provided data allowing estimation of a mean 25(OH)D weighed by sd as 21.0 (95% CI, 13.5, 28.5) ng/ml ( Supplemental Table 1).
Comparison of serum 25(OH)D between GCS users and nonusers
Twelve studies including a total of 271 GCS users and 251 steroid-naive controls (123 healthy, 128 with disease) were available to compare serum 25(OH)D between GCS users and nonusers ( Supplemental Table 2). A meta-analysis (Fig. 1) indicated that the SMD was not significant [SMD = −0.2 (95% CI, −0.4, 0.1) ng/ml]. A moderate degree of heterogeneity, however, was evident between studies (I2 = 53.9%).
Fig. 1.
Random effects meta-analysis comparing 25(OH)D concentrations between GCS users and nonusers (both healthy and disease controls). I2 = 53.9%; P = 0.011; test of SMD = 0, z = 1.06, P = 0.289.
Fig. 1.
Random effects meta-analysis comparing 25(OH)D concentrations between GCS users and nonusers (both healthy and disease controls). I2 = 53.9%; P = 0.011; test of SMD = 0, z = 1.06, P = 0.289.
Meta-analyses also examined relationships between GCS users and healthy controls, and between GCS users and disease controls (Figs. 2 and 3). Serum 25(OH)D in GCS users was significantly below that of healthy controls [SMD = −0.5 (95% CI, −1.0, −0.1) ng/ml; P = 0.03]. Heterogeneity (I2 = 56.4%) was moderate in this analysis. In contrast, there was no difference in serum 25(OH)D between GCS users and disease controls [SMD = 0.0 (95% CI, −0.2, 0.3) ng/ml]. There was a low degree of heterogeneity between these studies (I2 = 16.2%).
Fig. 2.
Random effects meta-analysis comparing 25(OH)D concentrations between GCS users and healthy control nonusers. I2 = 56.4%; P = 0.057; test of SMD = 0, z = 2.13, P = 0.033.
Fig. 2.
Random effects meta-analysis comparing 25(OH)D concentrations between GCS users and healthy control nonusers. I2 = 56.4%; P = 0.057; test of SMD = 0, z = 2.13, P = 0.033.
Fig. 3.
Random effects meta-analysis comparing 25(OH)D concentrations between GCS users and nonusers with active disease. I2 = 16.2%; P = 0.302; test of SMD = 0, z = 0.26, P = 0.798.
Fig. 3.
Random effects meta-analysis comparing 25(OH)D concentrations between GCS users and nonusers with active disease. I2 = 16.2%; P = 0.302; test of SMD = 0, z = 0.26, P = 0.798.
Comparison of serum 25(OH)D before and after GCS administration
Only two studies with a total of 33 participants could be analyzed to examine the difference in serum 25(OH)D concentration before and after GCS administration ( Supplemental Table 3). No significant change in serum 25(OH)D occurred after 6 months [SMD = −0.2 (95% CI, −0.7, 0.3) ng/ml]. The mean daily GCS dose given in each study, however, was very different. Where the mean GCS dose was 19.9 mg/d, the effect size was small to medium (34), whereas with a mean GCS dose of only 5 mg/d, no change in serum 25(OH)D concentrations was observed (35).
Discussion
Adults receiving GCS therapy appear frequently to have concentrations of serum 25(OH)D that are suboptimal for the prevention or management of GIO. Although neither weighted mean statistic [by sample size, 22.4 (95% CI, 19.4, 25.3) ng/ml; by sd, 21.0 (95% CI, 13.5, 28.5) ng/ml] fell below 20 ng/ml, the size of CI suggests that the true weighted mean statistic could indeed indicate deficiency. Furthermore, serum 25(OH)D in GCS users was on average −0.5 (95% CI, −1.0, −0.1) ng/ml lower than that found in healthy controls. This relationship was not evident between GCS users and disease controls, indicating that disease status may explain the difference in 25(OH)D between GCS users and healthy controls. These results are consistent with findings from a recent population study using data from National Health and Nutrition Examination Survey III; the authors determined that those using steroids were two times more likely to be vitamin D deficient (defined as 25(OH)D <10 ng/ml) compared with those not using steroids (31).
Prednisone not only increases the catabolism of 25(OH)D (8, 17, 36) but may also induce significant weight gain. Obesity may then compound the deleterious effects of GCS on vitamin D status because it is known that vitamin D sequesters in body fat (8), decreasing its bioavailability (37). The prevalence of obesity thus complicates assessment of the effects of GCS on vitamin D status. Nonetheless, it is clear that 25(OH)D was suboptimal in the GCS-treated cohorts examined here, suggesting that recommendations for vitamin D supplementation in people treated with GCS may need revision. Based on our weighted means in adults, which are in the range 16–24 ng/ml, 1800 IU/d (45 ÎĽg/d) of vitamin D supplementation would be required to achieve serum concentrations of 25(OH)D of at least 32 ng/ml (24). In comparison to this calculated requirement, The Endocrine Society recommends a higher daily dose for adult steroid users [3000–6000 IU/d (75–150 ÎĽg/d)] (8), whereas the recommendations of the American College of Rheumatology (15) are considerably lower [800–1000 IU/d (20–25 ÎĽg/d)].
It is essential to measure 25(OH)D concentrations in individuals as they commence GCS therapy because there may be considerable variation in their vitamin D status, and hence their requirement for supplementation. Yet this review found several studies indicating a lack of assessment and/or treatment for bone health in patients commencing or receiving GCS therapy (38–41). In practice, it is probable that many patients commencing GCS do not have their 25(OH)D measured. Because bone is lost rapidly during first few months of GCS treatment (1), it would be prudent to set vitamin D recommendations for adults at or above 2000 IU/d (50 ÎĽg/d) to achieve optimal levels of 25(OH)D at this critical time. Exemptions may be appropriate where an individual is at risk of hypercalciuria and hypercalcemia, for example in patients with sarcoidosis (42). This amount of vitamin D is well below the safe upper limit of vitamin D intake [4000 IU (100 ÎĽg) per day for most adults] as determined by the Institute of Medicine (43). The safe upper limit of vitamin D intake has, however, been a matter of much contention, and for many patients at risk of deficiency, an upper limit as high as 10,000 IU (250 ÎĽg) has been proposed (8). A dose at this level has no detrimental effects on serum calcium or urinary calcium excretion (44). Moreover, vitamin D toxicity appears rare. Severe adverse effects are not seen until serum 25(OH)D rises above 700 nmol/liter (45). Very high bolus doses, however, are not advised. A recent Australian study noted adverse effects when elderly women were given 500,000 IU (12,500 ÎĽg) of vitamin D in a single oral annual dose, a single dose 10 times higher than that established as safe in previous trials. This nonphysiological dose increased basal 25(OH)D from a median of 49 to 120 nmol/liter within 1 month, and although no serious toxicity was reported, a significant increase in the rate of falls and fractures was detected (46). These outcomes appeared due to the single, very large dose given rather than to the serum 25(OH)D concentrations achieved.
This paper provides the first meta-analysis of serum 25(OH)D concentrations in patients receiving GCS. The use of weighted mean 25(OH)D statistics increases the clinical significance of this research and provides evidence for recommendations for vitamin D supplementation during GCS treatment. The meta-analysis is not without its limitations. Although unique, this review provides level III quality evidence at best because it mainly draws on cross-sectional measures of 25(OH)D. Non-English publications were excluded, which may overestimate the effect by 2% (47). Unpublished communications were also not reviewed as advised by Schlesselman (48).
With the exception of one analysis, a moderate degree of heterogeneity, both qualitatively and quantitatively, was evident among reviewed studies. This is inevitable because GCS are used widely across a diverse range of cohorts varying in age, disease types, and locality. Although this level of heterogeneity is held statistically to reduce the generalizability of a meta-analysis; it can conversely be argued that from a clinical viewpoint the diverse range of populations included in the analysis should increase generalizability. It can be noted that heterogeneity was low (I2 = 16.2%) in the analysis comparing 25(OH)D concentrations in GCS users vs. nonusers with disease. Because there was no significant difference between serum 25(OH)D between these groups, disease status may account for the observed difference in 25(OH)D concentrations between GCS users and healthy controls. Overall, the quality of studies used in this analysis was assessed as "neutral." This rating appeared more reflective of study reporting than of study design and methods because cross-sectional studies reviewed often provided insufficient description of their methods. Another key limitation was the dearth of information in studies regarding sun exposure and seasonal variation in serum 25(OH)D. These factors were often not measured because reviewed studies addressed very different research questions to our own. Only two studies were designed to assess the effect of GCS on 25(OH)D with a high level of evidence; these were studies where 25(OH)D concentrations were measured before and after GCS administration. Moreover, in studies where 25(OH)D was not the primary outcome measure, other key confounders were not adjusted for. Therefore, this review highlights the need for appropriately designed, longitudinal clinical studies to investigate the true effect of GCS on 25(OH)D concentrations.
Conclusion
This meta-analysis demonstrates that most adults receiving GCS treatment for a variety of disorders have suboptimal 25(OH)D concentrations. Recommendations for vitamin D supplementation need to be adjusted accordingly. The weighted mean 25(OH)D value obtained by meta-analysis suggests that vitamin D supplementation should, at a minimum, be 1800 IU/d (45 ÎĽg/d) for adult patients receiving GCS therapy.
Acknowledgments
Disclosure Summary: The authors have nothing to disclose.
Abbreviations
-
CI
-
GCS
-
GIO
glucocorticoid-induced osteoporosis
-
25(OH)D
-
SMD
standardized mean difference.
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