AJPB

Vitamin D Deficiency Treatment Patterns in Academic Urban Medical Center | Page 2

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
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.
1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3)266-281.

2. Dawson-Hughes B, Mithal A, Bonjour JP, et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 2010;21(7):1151-1154.

3. Bruce DG, St John A, Nicklason F, Goldswain PR. Secondary hyperparathyroidism in patients from Western Australia with hip fracture: relationship to type of hip fracture, renal function, and vitamin D deficiency. J Am Geriatr Soc. 1999; 47(3):354-359.

4. LeBoff MS, Hawkes WG, Glowacki J, Yu-Yahiro J, Hurwitz S, Magaziner J. Vitamin D-deficiency and post-fracture changes in lower extremity function and falls in women with hip fractures. Osteoporos Int. 2008;19(9):1283-1290.

5. LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281(16):1505-1511.

6. Robbins J, Aragaki AK, Kooperberg C, et al. Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA. 2007;298(20):2389-2398.

7. Glowacki J, Harris MB, Simon J, et al. Brigham fracture intervention team initiatives for hospital patients with hip fractures: a paradigm shift. Published online. Int J Endocrinol. 2010;2010:590751.

8. Watkins RR, Yamshchikov AV, Lemonovich TL, Salata RA. The role of vitamin D deficiency in sepsis and potential therapeutic implications. J Infect. 2011;63(5): 321-326.

. Braun A, Chang D, Mahadevappa K, et al. Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med. 2011;39(4): 671-677.

10. Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med. 2012;40(1):63-72.

11. Ginde AA, Camargo CA Jr, Shapiro NI. Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. Acad Emerg Med. 2011;18(5):551-554.

12. Grant WB. Vitamin D supplementation could reduce risk of sepsis in infants. World J Pediatr. 2010;6(2):185.

13. Jeng L, Yamshchikov AV, Judd SE, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;7:28.

14. Grant WB, Schuitemaker GE. Health benefits of higher serum 25-hydroxyvitamin D levels in The Netherlands. J Steroid Biochem Mol Biol. 2010;121(1-2):456-458.

15. Grant WB, Cross HS, Garland CF, et al. Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe. Prog Biophys Mol Biol. 2009;99(2-3):104-113.

16. Grant WB, Garland CF. The health benefits of vitamin D greatly outweigh the health risks. Bioessays. 2008;30(5):506-507.

17. Grant WB, Garland CF, Gorham ED. An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day. Recent Results Cancer Res. 2007;174:225-234.

18. Youssef D, Bailey B, El Abbassi A, et al. Healthcare costs of Staphylococcus aureus and Clostridium difficile infections in veterans: role of vitamin D deficiency. Epidemiol Infect. 2010;138(9):1322-1327.

19. Bailey BA, Manning T, Peiris AN. Vitamin D testing patterns among six Veterans Medical Centers in the Southeastern United States: links with medical costs. Mil Med. 2012;177(1):70-76.

20. Matthews LR, Ahmed Y, Wilson KL, Griggs DD, Danner OK. Worsening severity of vitamin D deficiency is associated with increased length of stay, surgical intensive care unit cost, and mortality rate in surgical intensive care unit patients. Am J Surg. 2012;204(1):37-43.

21. Saliba W, Barnett O, Rennert HS, Rennert G. The risk of all-cause mortality is inversely related to serum 25(OH)D levels. J Clin Endocrinol Metab. 2012;97(8): 2792-2798.

22. Pilz S, Dobnig H, Tomaschitz A, et al. Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. J Clin Endocrinol Metab. 2012;97(4):E653-E657.

23. Eaton CB, Young A, Allison MA, et al. Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women’s Health Initiative (WHI). Am J Clin Nutr. 2011;94(6):1471-1478.

24. Harris SS, Dawson-Hughes B. Reduced sun exposure does not explain the inverse association of 25-hydroxyvitamin D with percent body fat in older adults. J Clin Endocrinol Metab. 2007;92(8):3155-3157.

25. Harris SS. Vitamin D and African Americans. J Nutr. 2006;136(4):1126-1129.

26. Giovannucci E, Liu Y, Willett WC. Cancer incidence and mortality and vitamin D in black and white male health professionals. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2467-2472.

27. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds; Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2010.

28. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009;19(7):468-483.

29. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.

30. van Walraven C, Austin PC, Jennings A, Quan H, Forster AJ. A modification of the Elixhauser comorbidity measures into a point system for hospital death using administrative data. Med Care. 2009;47(6):626-633.

31. Gordon CM, Feldman HA, Sinclair L, et al. Prevalence of vitamin D deficiency among healthy infants and toddlers. Arch Pediatr Adolesc Med. 2008;162(6): 505-512.

32. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009; 169(6):626-632.

33. Garland CF, Gorham ED, Baggerly CA, Garland FC. Re: prospective study of vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2008; 100(11):826-827.

34. Garland CF,Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96(2):252-261.

35. Garland CF, Garland FC, Gorham ED. Can colon cancer incidence and death rates be reduced with calcium and vitamin D? Am J Clin Nutr. 1991;54(1) (suppl):193S-201S.

36. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. 1989;2(8673):1176-1178.

37. Egan KM, Signorello LB, Munro HM, Hargreaves MK, Hollis BW, Blot WJ. Vitamin D insufficiency among African-Americans in the southeastern United States: implications for cancer disparities (United States). Cancer Causes Control. 2008;19(5):527-535.

38. Dong Y, Pollock N, Stallmann-Jorgensen IS, et al. Low 25-hydroxyvitamin D levels in adolescents: race, season, adiposity, physical activity, and fitness. Pediatrics. 2010;125(6):1104-1111.

39. Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Endocrinol Metab Clin North Am. 2010; 39(2):287-301.

40. US Preventive Services Task Force. Folic acid for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(9):626-631.

41. Wehby GL, Castilla EE, Lopez-Camelo JS, Murray JC. Predictors of multivitamin use during pregnancy in Brazil. Int J Public Health. 2009;54(2):78-87.

42. Wilson RD, Johnson JA, Wyatt P, et al; Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada and The Motherrisk Program. Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can. 2007;29(12): 1003-1026.

43. Czeizel AE. Experience of the Hungarian Preconception Service between 1984 and 2010. Eur J Obstet Gynecol Reprod Biol. 2012;161(1):18-25.

44. Czeizel AE. Periconceptional folic acid-containing multivitamin supplementation for the prevention of neural tube defects and cardiovascular malformations. Ann Nutr Metab. 2011;59(1):38-40.

45. Czeizel AE, Bánhidy F. Vitamin supply in pregnancy for prevention of congenital birth defects. Curr Opin Clin Nutr Metab Care. 2011;14(3):291-296.

46. Czeizel AE, Dudás I, Paput L, Bánhidy F. Prevention of neural-tube defects with periconceptional folic acid, methylfolate, or multivitamins? Ann Nutr Metab. 2011;58(4):263-271.

47. Moyer VA, on behalf of the US Preventive Services Task Force. Prevention of falls in community-dwelling older adults: US preventive services task force recommendation statement. Ann Intern Med. 2012;157(3):197-204.

48. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin Dmediated human antimicrobial response. Science. 2006;311(5768):1770-1773.

49. Fabri M, Stenger S, Shin DM, et al. Vitamin D is required for IFN-gammamediated antimicrobial activity of human macrophages. Sci Transl Med. 2011; 3(104):104ra102.

50. Lee WM, Reines D, Watt GH, et al. Alterations in Gc levels and complexing in septic shock. Circ Shock. 1989;28(3):249-255.

51. Pène F, Grimaldi D, Zuber B, et al. Toll-like receptor 2 deficiency increases resistance to Pseudomonas aeruginosa pneumonia in the setting of sepsis-induced immune dysfunction. J Infect Dis. 2012;206(6):932-942.

52. Shea MK, Houston DK, Tooze JA, et al. Correlates and prevalence of insufficient 25-hydroxyvitamin D status in black and white older adults: the health, aging and body composition study. J Am Geriatr Soc. 2011;59(7):1165-1174.

53. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination survey, 1988-1994. Am J Clin Nutr. 2002;76(1):187-192.

54. Tseng M, Giri V, Bruner DW, Giovannucci E. Prevalence and correlates of vitamin D status in African American men. BMC Public Health. 2009;9:191.

55. Glowacki J, LeBoff MS, Kolatkar NS, Thornhill TS, Harris MB. Importance of vitamin D in hospital-based fracture care pathways. J Nutr Health Aging. 2008; 12(5):291-293.

56. Nelson HD, Haney EM, Dana T, Bougatsos C, Chou R. Screening for osteoporosis: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2010;153(2):99-111.

57. Abellan van Kan G, André E, Bischoff Ferrari HA, et al. Carla Task Force on Sarcopenia: propositions for clinical trials. J Nutr Health Aging. 2009;13(8): 700-707.

58. Whiting SJ, Calvo MS. Correcting poor vitamin D status: do older adults need higher repletion doses of vitamin D3 than younger adults? Mol Nutr Food Res. 2010;54(8):1077-1084.

59. Henry HL, Bouillon R, Norman AW, et al. 14th Vitamin D Workshop consensus on vitamin D nutritional guidelines. J Steroid Biochem Mol Biol. 2010;121(1-2): 4-6.

60. Hanley DA, Cranney A, Jones G, et al; Guidelines Committee of the Scientific Advisory Council of Osteoporosis Canada. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ. 2010;182(12): E610-E618.

61. Kohn LT, Corrigan JM, Donadlson MS, eds; Committee on Quality of Health Care in America, Institute of Medicine. To Err Is Human: Building a Safer Health System. Washington, DC: National Academies Press; 2000.

62. McGlynn EA, Asch SM, Adams J, et al. The quality of health care delivered to adults in the United States. N Engl J Med. 2003;348(26):2635-2645.

63. Orrico KB. Sources and types of discrepancies between electronic medical records and actual outpatient medication use. J Manag Care Pharm. 2008;14(7): 626-631.
Issue: January/February 2014
More on AJMC.COM