Vitamin D Deficiency Treatment Patterns in Academic Urban Medical Center

Abstract

OBJECTIVE

Assess racial/ethnic and sex differences in treatment of vitamin D deficiency with high dose ergocalciferol (‘vitamin D2’) or other forms of vitamin D in a northeastern U.S. 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) deficiency (25OHD < 20 ng/ml) from 2004–2008.

METHODS

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

RESULTS

Among 2,140 patients without renal disease and 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 at a higher frequency than whites, 37.8% 38.4% and 30.9%, respectively, p=0.003. The vitamin D prescription rate for women versus men was 26.3% and 7.5%, respectively, p=0.04. In a fully adjusted model, no difference in prescription likelihood for blacks and whites [OR=1.18 95% CI, 0.88–1.58; p=0.29] or Hispanics and whites was noted [OR=1.01 95% CI, 0.70–1.45;p=0.73]. Similarly, fully adjusted model showed no difference in prescription likelihood for females and males [OR=1.23 95% CI, 0.93–1.63; p=0.12].

CONCLUSIONS

Among primary care patients with vitamin D deficiency, vitamin D supplementation was low and white patients were less likely to receive vitamin D treatment than blacks or Hispanics. Interventions to correct the high prevalence of vitamin D deficiency should address the markedly low rate of vitamin D prescribing when 25OHD levels are measured.

INTRODUCTION

Vitamin D deficiency, defined as 25-hydroxyvitamin D (25OHD) level less than 20 ng/ml, is widespread due to low dietary intake, 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, blacks have 25OHD levels that 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 defined, the Institute of Medicine (IOM) recommends 25OHD above 20 ng/ml to ensure that 97.5% of the population are 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, limited data on sex, racial and ethnic differences in vitamin D prescribing for vitamin D deficiency exist. 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 (IRB) committee of Partners HealthCare System approved the study protocol. We used the Research Patient Data Registry (RPDR), a research and administrative data source designed to identify patients who meet specified criteria through a query tool. We identified 11,454 adult patients (ages 18 to 102 years) receiving care in one of 16 ambulatory practices affiliated with an academic medical center that had 25OHD levels checked between January 1, 2004 and December 31, 2008. The present study is restricted to a single clinic because it represents the most demographically diverse clinic. With the largest patient population of the 16 ambulatory practices, it has 31attending physicians, two 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 of racial/ethnic categories other than non-Hispanic black, Hispanic, and non-Hispanic white because of small numbers and/or patients had missing race/ethnicity data (Figure 1).

Figure 1.

Selection of patients in the primary care clinic with at least one 25OHD level

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 level during the study period to ensure that enrollees were regular ambulatory patients in this system. From these, we identified 2,140 patients with 25OHD < 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 2,140 eligible patients with 25OHD deficiency for our electronic medical record review.

Medical Record Review

For each participant, we abstracted electronic medical record 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 patient’s 25OHD level, date of 25OHD level, type of vitamin D prescribed within 30 days of 25OHD level, and date of vitamin D prescription.

Performance Measures

For this study, we selected the measure of treating vitamin D deficiency with a prescription of 50,000 units once weekly (7140 IU/day) or other forms of vitamin D including calcium/ergocalciferol (‘vitamin D2’) 200–400 IU or calcium/cholecalciferol 200–400 IU, cholecalciferol 400 IU – 1000 IU, or ergocalciferol 400 IU–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.³⁹

Data regarding treatment were obtained from patients’ electronic medical record. We analyzed whether 50,000 IU 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. Elixhauser 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 following document (http://journals.lww.com/lww-medicalcare/Abstract/2009/06000/A_Modification_of_the_Elixhauser_Comorbidity.4.aspx). The score was calculated based on the ICD-9 codes of patients’ diseases documented on the day of the vitamin D test or on the day nearest the day 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.²⁹

Statistical Analysis

We evaluated the frequency of different types of vitamin D supplements 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 of high-dose vitamin D or other forms of vitamin D within 30 days of a laboratory diagnosis of serum 25OHD deficiency. Insurance status is dichotomized as Medicare, Medicaid, and self-pay versus private insurance. Age is dichotomized as <65 years old and ≥ 65 years old. Comorbidity score is dichotomized as ≤0 and >0 based on the median score of zero for Elixhauser commordity score 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 to adjust for patients’ age, sex, insurance status, and Elixhauser comorbidity score. For each patient’s characteristic we report adjusted odds ratios (OR) and 95% confidence intervals 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, NC) for the analysis.

RESULTS

Baseline Patient Characteristics

Among the 2,140 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). More women than men had vitamin D deficiency for blacks, whites, and Hispanics (women:83.7%;70.1%; 80.8%, respectively; men: 16.3%;29.9%; 19.2%, respectively; Table 1). Most patients were younger than 65 (blacks 76.8%; whites 67.9%; Hispanics 79.3%; Table 1).

Table 1.

Vitamin D Deficiency Subjects’ Characteristics^*

Characteristic	Black (N=534)	White (N=1278)	Hispanic (N=328)
Age (years), mean(SD)	53.0(16.6)	57.8(15.8)	50.9(16.1)
Age (years)
<65	410(76.8)	868(67.9)	260(79.3)
≥65	124(23.2)	410(32.1)	68(20.7)
Men	87(16.3)	382(29.9)	63(19.2)
Women	447(83.7)	896(70.1)	265(80.8)
25(OH)D ng/ml, mean(SD)
Overall	12.1(4.9)	13.5(4.3)	13.6(4.7)
Men	12.2(5.0)	13.8(4.6)	13.0(5.0)
Women	12.1(4.9)	13.9(4.5)	13.4(4.3)
Insurance
Private	141(26.4)	564(44.1)	50(15.2)
Othera	280(52.4)	587(45.9)	238(72.6)
Unknown	113(21.2)	127(9.9)	40(12.2)
Elixhauser Total Points
≤0	207(38.8)	357(27.9)	144(43.9)
>0	147(27.5)	485(37.9)	54(16.5)
Unknown	180(33.7)	436(34.1)	130(39.6)

^*number of patients(%) except when expressed as mean(SD)

^aMedicare, Medicaid, and self-pay

Comorbidities

Of patients with identified comorbidities and vitamin D deficiency, hypertension, the most common comorbidity, was present in 51.7% blacks; 37.2% whites, and 47.9% Hispanics.

Frequency and Likelihood of Vitamin D Therapy

Among the 11,454 patients tested for vitamin D status, 2,140 (18.7%) were 25OHD deficient (Figure 1). Overall 25(OH)D status for the 11,454 patients by race was n=number of patients, 25(OH)D [ng/ml, mean(SD)]: non-Hispanic black, n=1,604, 24.1(14.7); Hispanic, n=1,144, 28.0(20.2); white, n=8,706, 33.1(4.9). From these we identified 723 non-Hispanic black, Hispanic, or non-Hispanic white patients prescribed some type of vitamin D within 30 days of which 561 patients received at least one prescription dose of 50,000 IU ergocalciferol (Figure 1). 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 at a higher frequency than whites, 37.8% 38.4% and 30.9%, respectively, p=0.003 (Table 3). The vitamin D prescription rate for women versus men was 26.3% and 7.5%, respectively, p=0.04 (Table 3). In unadjusted analyses, 25OHD deficient women had 25% higher odds of getting a vitamin D prescription compared to men (p=0.03; Table 4).

Table 3.

Frequency of Subjects with Vitamin D Deficiency and No Renal Disease that Received Any Form of Vitamin D Prescription

Characteristic	Overall	Black	White	Hispanic	Overall Races P value	Overall Gender P value	P value Men	P value Women
All Patients Prescribed Vitamin D	723(33.8)	202(37.8)	395(30.9)	126(38.4)	0.003	0.04
Men Prescribed Vitamin D	160(7.5)	33(37.9)	107(28.0)	20(31.8)			0.18
Women Prescribed Vitamin D	563(26.3)	169(37.8)	288(32.1)	106(40)				0.003

^*number of patients(%)

Table 4.

Unadjusted and Adjusted Odds Ratios for Significant Predictors of Vitamin D Prescription for Vitamin D Deficiency in Patients Without Renal Disease

Subgroup	No. Patients	Unadjusted Odds Ratio (95% CI) Vitamin D Prescription	Adjusted Odds Ratio (95% CI) Vitamin D Prescriptiona
Race/ethnicity
White	1278	1.00	1.00
Black	534	1.36 [1.10–1.68]	1.18 [0.88–1.58]
Hispanic	328	1.39 [1.08–1.79]	1.01 [0.70–1.45]
Age, years
≥ 65	602	1.00	1.00
< 65	1538	0.87 [0.71–1.06]	0.89 [0.67–1.17]
Sex
Male	532	1.00	1.00
Female	1608	1.25[1.01–1.55]	1.23 [0.93–1.63]
Elixhauser comorbidity score
≤ 0	632	1.00	1.00
> 0	762	1.07 [0.84–1.36]	1.06 [0.82–1.35]

^aModel: Logistic regression with covariates of gender, race/ethnicity, age, Elixhauser comorbidity score, and insurance status

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=0.29] or Hispanics and whites [OR=1.01 95% CI, 0.70–1.45;p=0.73]. Similarly, fully adjusted model showed no difference in prescription likelihood for females and males [OR=1.23 95% CI, 0.93–1.63; p=0.12] (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.^30–38 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/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 of 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 U.S.

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 while adults 71 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 supplement treatment for identified vitamin D deficiency.³⁹ 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 blood level of 25OHD above 30 ng/ml.³⁹

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 pre-conception prescribing of multivitamin with folate for women of child-bearing age to reduce neural tube defects as recommended by US Preventive Services Task Force guidelines.^40–46 Studies of vitamin D prescribing patterns in six southeastern veteran medical centers have documented that veterans tested and effectively treated have the lowest yearly inpatient costs.¹⁹ Specifically, inpatient laboratory and pharmacy costs were twice as high among vitamin D deficient patients compared with non-vitamin D deficient patients and length of hospitalization was also longer for vitamin D deficient patients.¹⁹ Furthermore, if patients in this cohort are taking over-the-counter vitamin D or multivitamin, overall their 25OHD level is 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 no cause of secondary osteoporosis, 50% of them had extreme vitamin D deficiency (25OHD<= 12 ng/ml).⁵ Thus, the U.S. Preventive Task Force (USPTF) advises exercise or physical therapy and vitamin D supplementation to prevent falls in adults aged 65 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 health maintenance fracture prevention initiatives within the electronic health record (EHR).

The lower vitamin D treatment rates in men support 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. ^{56,56–58,58–60} Vitamin D may be overprescribed in light of IOM report that suggests that patients are vitamin D replete with 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 a third of patients with 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 et al.⁶² report that adults receive only 55% of recommended care with no significant difference in the recommended preventive care versus the recommended acute care provided.

Some limitations to our study exist. We examined patients receiving care in a multi-ethnic practice affiliated with a single large tertiary hospital. This practice was selected because it is representative of the most ethnically diverse primary care patient population (24.8% black, 47.7% white, 14.1% Hispanic) and it has 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 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 such as 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. Orrico et al.⁶³ noted that the most common discrepancy between EHR and actual outpatient medication use is the presence of an EHR medication that is no longer being taken by 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 use the concept of comorbidities as a proxy for the intensity of relationship between patient and doctor, there are likely factors in the patient-doctor interaction that 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.

Table 2.

Comorbidities of Patients with Vitamin D Deficiency and No Renal Disease^*

Characteristic	Overall (N=1396)	Black (N=354)	White (N=844)	Hispanic (N=198)
Overweight or Obesity	199(14.2)	80(22.6)	79(9.4)	40(20.2)
Hypertension	592(42.4)	183(51.7)	314(37.2)	95(48.0)
Type II Diabetes without complications	282(20.2)	90(25.4)	134(15.9)	58(29.3)
COPD	251(18.0)	66(18.6)	153(18.1)	32(16.2)

^*number of patients(%)

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 health care providers must integrate evidence-based practices for vitamin D supplementation into care pathways to prevent and treat vitamin D deficiency.