AJPB

Vitamin D Deficiency Treatment Patterns in Academic Urban Medical Center

Published Online: February 19, 2014
Paulette D. Chandler, MD, MPH; Edward L. Giovannucci, MD, ScD; Michelle A. Williams, ScD; Meryl S. LeBoff, MD; David W. Bates, MD, MSc; and LeRoi S. Hicks, MD, MPH
Objectives: To assess racial/ethnic and sex differences in treatment of vitamin D deficiency in a northeastern US ambulatory clinic of an academic urban medical center.

Study Design: Cross-sectional observational review of electronic medication prescribing records of patients with 25-hydroxyvitamin D (25OHD) defi ciency from 2004 to 2008.

Methods: Using multivariable logistic regression with adjustment for patients’ demographics and Elixhauser comorbidity score, we examined the association of sex and race/ethnicity with a prescription for at least 1 dose of vitamin D.

Results: Among 2140 patients without renal disease who were tested for 25OHD deficiency (25OHD <20 ng/mL), 66.2% received no vitamin D prescription for vitamin D deficiency. Blacks and Hispanics received vitamin D prescriptions more often than whites: 37.8% and 38.4% versus 30.9%, respectively (P = .003). The vitamin D prescription rate for women was 26.3% versus 7.5% for men (P = .003). In a fully adjusted model, no difference in prescription likelihood for blacks and whites (odds ratio [OR] = 1.18, 95% confidence interval [CI], 0.88-1.58; P = .29) or Hispanics and whites was noted (OR = 1.01, 95% CI, 0.70-1.45; P = .73). Similarly, the fully adjusted model showed no difference in prescription likelihood for women and men (OR = 1.23, 95% CI, 0.93-1.63; P = .12).

Conclusions: Among primary care patients with vitamin D deficiency, the rate of vitamin D supplementation was low. Interventions to correct the high prevalence of vitamin D defi ciency should address the markedly low rate of vitamin D prescribing when 25OHD levels are measured.

Am J Pharm Benefits. 2014;6(1):e1-e8
Vitamin D deficiency, defined as a 25-hydroxyvitamin D (25OHD) level less than 20 ng/mL, is widespread due to low dietary intake, low supplement use, and sun avoidance.1,2 Vitamin D deficiency is associated with a myriad of costly diseases including fractures,3-7 sepsis,8-13 and cancer.14-17 Higher healthcare costs associated with vitamin D deficiency are linked with increased length of hospital stay, surgical intensive care unit cost, and mortality rate.18-20 Furthermore, the risk of all-cause mortality is inversely related to 25OHD level.21-23 Overall, 25OHD levels among blacks tend to be one-third to one-half those of whites.24-26 As a result, 25OHD levels represent an important health issue in this group.

Serum 25OHD is a reliable method for evaluating vitamin D stores in patients. Although the desirable 25OHD range for patients needs to be more accurately defi ned, the Institute of Medicine (IOM) recommends that 25OHD be above 20 ng/mL to ensure that 97.5% of the population is vitamin D replete for optimal bone health.27 Higher levels may be needed to provide extraskeletal benefits.28 Furthermore, vitamin D supplementation can prevent and treat vitamin D deficiency.

To date, there are limited data on sex, racial, and ethnic differences in vitamin D prescribing for vitamin D deficiency. The goal of this study was to evaluate treatment of vitamin D deficiency (25OHD <20 ng/mL) in a racially diverse ambulatory practice affiliated with an academic urban medical center to determine the presence of racial/ethnic or sex disparities in use of vitamin D supplementation. Exploration of the process of ordering the test or determining why patients get the test is beyond the scope of this study.

METHODS

Study Setting and Participants


The Human Studies Institutional Review Board committee of Partners HealthCare System approved the study protocol. We used the Research Patient Data Registry, a research and administrative data source designed to identify patients who meet specified criteria, through a query tool. We identified 11,454 adult patients (aged 18-102 years) receiving care in 1 of 16 ambulatory practices affi liated with an academic medical center who had 25OHD levels checked between January 1, 2004, and December 31, 2008. We restricted the present study to a single clinic because it was the most demographically diverse clinic. With the largest patient population of the 16 ambulatory practices, it has 31 attending physicians, 2 nurse practitioners, and no physician assistants. Furthermore, it has the largest black population of the 16 practices (24.8% black, 47.7% white, 14.1% Hispanic). We eliminated 1790 patients belonging to racial/ethnic categories other than non-Hispanic black, Hispanic, and non-Hispanic white because of small numbers and/or because patients had missing race/ethnicity data (Figure).

From these cross-sectional data, we selected 11,454 self-identified non-Hispanic black, Hispanic, and non- Hispanic white patients who were seen in the same primary care clinic within the 12 months before their first 25OHD measurement during the study period to ensure that enrollees were regular ambulatory patients in this system. From this group, we identified 2140 patients with 25OHD less than 20 ng/mL and with no diagnosis of renal disease. Patients with renal disease were excluded based on Elixhauser criteria for renal failure. Thus, the final sample consisted of 2140 eligible patients with 25OHD deficiency for our electronic medical record (EMR) review.

Medical Record Review

For each participant, we abstracted EMR data including participants’ demographic and clinical characteristics. Data elements obtained from each record included patients’ self-identified race/ethnicity (non-Hispanic black, Hispanic, or non-Hispanic white), sex, insurance status, comorbid conditions, and age. For each patient we also obtained the 25OHD level, date of 25OHD measurement, type of vitamin D prescribed within 30 days of 25OHD measurement, and date of vitamin D prescription.

Performance Measures

For this study, we selected treatment of vitamin D defi ciency with a prescription of 50,000 units of ergocalciferol (vitamin D2) once weekly (7140 IU/day) or other forms of vitamin D including calcium/ergocalciferol 200 to 400 IU, cholecalciferol 400 to 1000 IU, or ergocalciferol 400 to 800 IU. The Endocrine Society Task Force guidelines state that all vitamin D–deficient adults should be treated with 50,000 IU of vitamin D2 or D3 once a week for 8 weeks or its equivalent of 6000 IU of vitamin D2 or D3 daily to achieve a blood level of 25OHD above 30 ng/mL.29 Data regarding treatment were obtained from each patient’s electronic medical record. We analyzed whether 50,000 IU of ergocalciferol or other forms of vitamin D was prescribed within 30 days of a 25OHD laboratory result less than 20 ng/mL.

A comorbidity index was calculated using the Elixhauser code method. The Elixhauser code method assigns points to 29 different diseases. Version 3.6 of Elixhauser codes was used (http://www.hcup-us.ahrq.gov/toolssoftware/ comorbidity/comorbidity.jsp). Points for each code were assigned based on the work of van Walraven and colleagues.30 The score was calculated based on the International Classification of Diseases, Ninth Revision codes for patients’ diseases documented on the day of the vitamin D test or on the day nearest that of the vitamin D test. Elixhauser comorbidity codes are condensed to a single numeric score that summarizes disease burden and is adequately discriminative for death in hospital. A higher score represents greater disease burden.30

Statistical Analysis

We evaluated how frequently different types of vitamin D supplements were prescribed within 30 days for patients with a laboratory diagnosis of serum 25OHD deficiency. We then developed a series of logistic regression models to examine the association of patients’ socioeconomic characteristics and comorbidities with the outcome of prescribing high-dose vitamin D or other forms of vitamin D within 30 days of a laboratory diagnosis of serum 25OHD deficiency. Insurance status was dichotomized as Medicare, Medicaid, and self-pay versus private insurance. Age was dichotomized as less than 65 years and 65 years or older. Comorbidity score was dichotomized as 0 and greater than 0 based on the median Elixhauser comorbidity score of 0 for the study population. We then conducted multivariable logistic regression modeling to examine the independent association of patients’ race/ethnicity with differences in prescribing of high-dose vitamin D or other forms of vitamin D, adjusting for patient age, sex, insurance status, and Elixhauser comorbidity score. For each patient’s characteristics, we report adjusted odds ratios (ORs) and 95% confidence intervals (CIs) representing the odds of being prescribed high-dose vitamin D or some other form of vitamin D. We used SAS version 9.2 (SAS Institute, Inc, Cary, North Carolina) for the analysis.

RESULTS

Baseline Patient Characteristics

Among the 2140 patients evaluated for vitamin D deficiency, non-Hispanic white patients were significantly older, more likely to be privately insured, and had more comorbid diseases (Table 1). Among blacks, whites, and Hispanics, more women than men had vitamin D deficiency (women: 83.7%, 70.1%, and 80.8%, respectively; men: 16.3%, 29.9%, and 19.2%, respectively; Table 1). Most patients were aged less than 65 years (blacks 76.8%, whites 67.9%, Hispanics 79.3%; Table 1).

Comorbidities

Of patients with identified comorbidities and vitamin D deficiency (n = 1396), hypertension was the most common comorbidity, present in 51.7% of blacks; 37.2% of whites, and 48% of Hispanics (Table 2). (Note: comorbidities were not available for all patients.)

Frequency and Likelihood of Vitamin D Therapy

Among the 11,454 patients tested for vitamin D status, 2140 (18.7%) were 25OHD deficient (Figure). From this group, we identified 723 non-Hispanic black, Hispanic, or non-Hispanic white patients prescribed some type of vitamin D within 30 days, 561 of whom received at least 1 prescription dose of 50,000 IU of ergocalciferol (Figure). High-dose ergocalciferol represented 77.6% of vitamin D medications prescribed during the 30-day period. Overall, only 33.8% of vitamin D–deficient patients received a vitamin D prescription within 30 days of diagnosis of vitamin D deficiency. Blacks and Hispanics received vitamin D prescriptions more often than whites: 37.8%, 38.4%, and 30.9%, respectively (P = .003; Table 3). The vitamin D prescription rate for women versus men was 26.3% and 7.5%, respectively (P = .003; Table 3). In unadjusted analyses, 25OHD-deficient women had 25% higher odds of getting a vitamin D prescription compared with men (P = .03; Table 4).

We assessed whether race/ethnicity, age, sex, Elixhauser comorbidity score, or insurance status modified the likelihood of receiving a vitamin D prescription. In a fully adjusted model, we found no difference in prescription likelihood for blacks and whites (OR = 1.18, 95% CI, 0.88-1.58; P = .29) or Hispanics and whites (OR = 1.01, 95% CI, 0.70-1.45; P = .73). Similarly, the fully adjusted model showed no difference in prescription likelihood for females and males (OR = 1.23, 95% CI, 0.93-1.63; P = .12) (Table 4). Comorbidities did not influence likelihood of receiving a vitamin D prescription (Table 4).

DISCUSSION

Many studies have documented disparities in vitamin D deficiency prevalence.31-39 Correction of vitamin D deficiency in ambulatory care, an important strategy to reduce vitamin D deficiency disparities, is less well studied. In this large, racially and ethnically diverse cohort of primary care patients with 25OHD deficiency, 66.2% of patients did not receive a vitamin D prescription for vitamin D deficiency. Furthermore, in terms of prescriptions given, male patients received fewer prescriptions. Lastly, the rate of vitamin D prescriptions for blacks and Hispanics was significantly higher than that for whites,and white women received fewer prescriptions than black and Hispanic women. To our knowledge, this is the first examination of vitamin D prescribing for 25OHD deficiency among patients in a primary care clinic in the United States.

Given the recent IOM report, we chose the threshold of 20 ng/mL to determine appropriateness of therapy in order to be consistent with the most conservative guidelines. 27 The IOM recommends that children and adults (1-70 years) need 600 IU/day of vitamin D, whereas adults 71 years and older need 800 IU of vitamin D. In contrast to the IOM, the Endocrine Society Task Force recommends screening for vitamin D deficiency with serum 25OHD in individuals at risk for deficiency and treatment with supplements when vitamin D deficiency is identified. 29 The Task Force suggests using either vitamin D2 or vitamin D3 for the treatment of vitamin D deficiency. The Task Force guidelines state that all vitamin D-deficient adults should be treated with 50,000 IU of vitamin D2 or D3 once a week for 8 weeks or its equivalent of 6000 IU of vitamin D2 or D3 daily to achieve a 25OHD blood level above 30 ng/mL.29

In this study population, evaluation of vitamin D therapy was limited to documented vitamin D prescriptions. The overall low use of vitamin D prescriptions for vitamin D deficiency agrees with the supplement use research. There is low use of appropriate vitamin supplementation for evidence-based clinical benefits such as preconception prescribing of a multivitamin with folate for women of child-bearing age to reduce neural tube defects, as recommended by US Preventive Services Task Force (USPSTF) guidelines.40-46 Studies of vitamin D prescribing patterns in 6 southeastern VA (Department of Veterans Affairs) medical centers have documented that veterans who were tested and effectively treated had the lowest yearly inpatient costs.19 Specifically, inpatient laboratory and pharmacy costs were twice as high among vitamin D-deficient patients compared with patients not deficient in vitamin D; length of hospitalization was also longer for vitamin D-deficient patients.19 Furthermore, if patients in this cohort were taking over-the-counter vitamin D or a multivitamin, their overall 25OHD level was still low.

The consequences of chronic vitamin D deficiency— osteomalacia, osteopenia, and osteoporosis—are each associated with increased fracture risk.3 In an evaluation of community-dwelling postmenopausal women with hip fracture and without secondary osteoporosis as a cause, 50% had extreme vitamin D deficiency (25OHD <12 ng/mL).5 Thus, the USPSTF advises exercise or physical therapy and vitamin D supplementation to prevent falls in adults 65 years or older who are at increased risk for falls.47

Additionally, the risk of all-cause mortality is inversely related to 25OHD level.21-23 Low serum 25OHD at critical care initiation is associated with increased mortality and a higher rate of sepsis.9,10 Vitamin D may be associated with sepsis through its modulatory role in the inflammatory pathways of sepsis and local immune response to pathogens.12,13,48-51

Healthcare providers have a unique opportunity to diagnose and treat vitamin D deficiency. In blacks and whites, studies have associated a lack of vitamin D supplementation with lower vitamin D levels.52,53 Even among black men and women taking vitamin D supplements, the prevalence of vitamin D deficiency is greater than in whites.53,54 In a perioperative inpatient intervention program for hip fracture patients, patients who were provided with information and questions for their primary care physician about osteoporosis were more likely to receive interventions such as vitamin D deficiency treatment.55 Future studies can evaluate the efficacy of outpatient computer-assisted enhancement of fracture prevention initiatives within the EMR.

The lower vitamin D treatment rates in men are in agreement with earlier studies. Prior literature suggests that vitamin D deficiency may be ignored in men unless they have underlying risk factors for poor bone health such as chronic steroid use.56-60 Vitamin D may be overprescribed in light of IOM report that suggests that patients are vitamin D replete when they have a 25OHD level greater than or equal to 20 ng/mL.27 Yet this study suggests that vitamin D deficiency is being undertreated in all patients, given that only about one-third of patients with a 25OHD level less than 20 ng/mL received some form of vitamin D prescription within 30 days. The low prescription rate confirms low treatment of vitamin D deficiency. A 2000 IOM report estimates that medication errors are among the most common medical mistakes and highlights that errors are most common when prescribing and administering medications.61 Furthermore, McGlynn and colleagues62 report that adults receive only 55% of recommended care, with no significant difference in the recommended preventive care versus the recommended acute care provided.

There are some limitations to our study. We examined patients receiving care in a multiethnic practice affiliated with a single large tertiary hospital. This practice was selected because it was representative of the most ethnically diverse primary care patient population (24.8% black, 47.7% white, 14.1% Hispanic) and it had the largest patient population, with 31 attending physicians and 2 nurse practitioners. Our findings may not be generalizable outside of similar academic settings. Interpretation of these findings is limited by the absence of information regarding the indication for testing. Determinants of the decision to test for vitamin D deficiency may influence vitamin D deficiency treatment patterns. Yet the most common indications for checking 25OHD (eg, osteoporosis) would prompt treatment of vitamin D deficiency. Another limitation relates to electronic prescribing as our primary predictor of treatment of vitamin D deficiency; we may have underestimated treatment if a significant number of patients were told to take over-the-counter supplementation. Orrico63 noted that the most common discrepancy between EMR and actual outpatient medication use is the presence of an EMR medication that is no longer being taken by the patient. They also noted that the most common patient-generated discrepancy was the omission of a multivitamin. However, the high frequency of vitamin D deficiency in this population suggests that patients are not ingesting adequate amounts of vitamin D.

Although we used comorbidities as a proxy for the intensity of relationship between patient and doctor, factors in the patient-doctor interaction likely are not represented in our model. Finally, performance measures are inherently limited in their ability to predict quality and outcomes, and measures of treatment of vitamin D deficiency have not yet been validated through large-scale implementation.

In summary, we found no difference in adjusted results by race/ethnicity or sex for vitamin D prescribing for vitamin D deficiency. Overall, there were very low rates of treatment for vitamin D deficiency in this study. Vitamin D deficiency is associated with increased fracture risk and mortality. Future work should focus on increasing vitamin D prescribing for vitamin D deficiency.

Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether the association between hypovitaminosis D and death is causal and reversible, and whether treatment of vitamin D deficiency reduces sepsis risk.

Take-Away Points

Overall, we found low vitamin D prescribing rates for identified vitamin D deficiency. 
  • A knowledge-to-action gap exists for prompt treatment of vitamin D deficiency and contributes to chronic vitamin D deficiency. 

  • Vitamin D supplementation is a tolerable low-cost intervention with strong evidence for fracture prevention and possible reduction in mortality.

  • Physicians and other healthcare providers must integrate evidence-based practices for vitamin D supplementation into care pathways to prevent and treat vitamin D deficiency.
Author Affiliations: Brigham and Women’s Hospital, Boston, MA (PDC, MSL, DWB); Harvard Medical School (ELG); Harvard School of Public Health (MAW); University of Massachusetts - Medicine (LSH).

Funding Source: This study was funded via a grant from the National Cancer Institute (NCI U01CA138962). 

Author Disclosures: The authors (PDC, ELG, MAW, MSL, DWB, LSH) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (PDC, ELG, LSH, DWB, MSL); acquisition of data (PDC, MSL); analysis and interpretation of data (PDC, MAW, ELG, LSH, DWB, MSL); drafting of the manuscript (PDC, LSH); critical revision of the manuscript for important intellectual content (PDC, MAW, ELG, LSH, DWB, MSL); statistical analysis (PDC); provision of study materials or patients (PDC); obtaining funding (PDC); administrative, technical, or logistic support (PDC, DWB); supervision (PDC, MAW).

Address correspondence to: Paulette D. Chandler, MD, Brigham and Women’s Hospital, Phyllis Jen Center of Primary Care, Ste G, 75 Francis St, Boston, MA 02115. E-mail: pchandler@partners.org.
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