- Email: [email protected]
Insufficiency Practice Patterns in a Veterans Health Administration Long-Term Care Population: A Retrospective Analysis
Vitamin D Deficiency/Insufficiency Practice Patterns in a Veterans Health Administration Long-Term Care Population: A Retrospective Analysis Kathryn K. Braddy, PharmD, Syed N. Imam, MD, Kavita R. Palla, PharmD, and Todd A. Lee, PharmD, PhD
Objectives: To evaluate the prevalence of vitamin D deficiency/insufficiency in long-term care patients at a Veterans Health Administration (VHA) hospital and to assess treatment and follow-up of low vitamin D levels. Design: Observational cohort study.
of patients with low vitamin D levels received some form of vitamin D therapy, whereas 43% received treatment as well as follow-up evaluation of vitamin D status within 3 months. Only 13% received a formulation of vitamin D appropriate for the severity of their deficiency/insufficiency with concurrent calcium supplementation and had a repeat vitamin D level within 3 months.
Setting: VA hospital extended care center (ECC). Participants: 2218 ECC patients between January 2001 and December 2006 were screened. Measurement: Serum 25-hydroxyvitamin D (25[OH]D) level, vitamin D therapy regimen, time to follow-up, documented adverse event to vitamin D therapy. Results: Of 2218 patients admitted to the ECC during the study period, 229 (10%) had a vitamin D level measured. Among these 229 patients, 49% were vitamin D sufficient (25[OH]D $30 ng/mL), 14% were insufficient (25[OH]D 5 21–29 ng/mL), and 37% were deficient (25[OH]D #20 ng/mL). Sixty-nine percent
Vitamin D is a key factor influencing calcium and phosphorus homeostasis and bone health. Serum 25-hydroxyvitamin D (25[OH]D) is the vitamin D metabolite measured clinically to assess vitamin D status.1 Reference values for serum 25(OH)D are based on adverse health outcomes rather than population-based reference values, which vary based on geographical region, as well as lifestyle and environmental factors.2 Vitamin D deficiency is defined as 25(OH)D levels of 20 ng/mL or less, whereas levels between 21 and 29 ng/
Edward Hines, Jr. VA Hospital, Hines, IL (K.K.B., S.N.I., K.R.P., T.A.L.); VA Maryland Health Care System, Baltimore, MD (K.K.B.). Address correspondence to Kathryn K. Braddy, PharmD, VA Maryland Health Care System, 10 N. Greene Street (119), Baltimore, MD 21201. E-mail: kathryn. [email protected]
Published by Elsevier, Inc. on behalf of the American Medical Directors Association DOI:10.1016/j.jamda.2009.08.010 ORIGINAL STUDIES
Conclusion: Vitamin D levels were measured infrequently in long-term care patients. Among those monitored, the rate of vitamin D deficiency/insufficiency is high. Few patients with low vitamin D status received proper treatment and follow-up. These data support the need to educate physicians regarding the high prevalence of vitamin D insufficiency/deficiency among long-term care patients to ensure that patients with low vitamin D levels are identified and treated appropriately. (J Am Med Dir Assoc 2009; 10: 653–657) Keywords: Vitamin D; long-term care; vitamin D insufficiency; vitamin D deficiency
mL are deemed insufficient; 25(OH)D levels 30 ng/mL or higher are considered sufficient.1 Vitamin D deficiency/insufficiency is a widespread problem in the elderly, particularly in institutionalized and geriatric populations. The prevalence of vitamin D deficiency is estimated at 41% in outpatients aged 49 to 83 years,3 and although there are no definitive estimates of the prevalence of vitamin D deficiency in nursing home patients, studies indicate that 25(OH)D levels are significantly lower in nursing home patients compared with community-dwelling elderly.4 The main sources of vitamin D are exposure to sunlight and limited dietary sources, such as fatty fish and egg yolks, and certain fortified foods3. Vitamin D levels decline as a result of multiple factors associated with aging, including decreased solar exposure, decreased dietary intake of vitamin D, and decreased dermal production of vitamin D, as well as decreased conversion of vitamin D to its active form by the kidneys owing to age-related decline in renal function.5 Braddy et al 653
Low serum vitamin D leads to impaired calcium metabolism, in turn triggering secondary hyperparathyroidism, increased bone turnover, and progressive bone loss.3 Osteoporosis is a leading cause of morbidity and mortality in the elderly, although largely undetected in men. Males who suffer osteoporotic fracture, however, have a worse prognosis than age-matched females.6 In patients with osteoporosis and/or fracture, the prevalence of low vitamin D levels appears to be even higher than in the general population; 76% of osteoporotic patients had very low vitamin D levels in a study conducted by Passeri et al,7 and Simonelli et al8 reported that 97% of patients in a study of patients 50 years and older hospitalized for nontraumatic fracture had 25(OH)D levels lower than 30 ng/mL. Furthermore, recent meta-analyses of randomized controlled trials concluded that vitamin D supplementation appears to reduce the risk of falls and fractures among older individuals.9,10 Vitamin D is an important factor in optimal muscle strength and function. Ongoing research also suggests benefits of vitamin D supplementation in several other chronic illnesses, including many cancers, autoimmune diseases, infectious diseases, cardiovascular disease, and possibly psychiatric illnesses such as depression and schizophrenia. Prior research has shown that vitamin D supplementation can reverse the negative effects of hypovitaminosis D on bone mineral density. Currently, there are no consensus guidelines on proper treatment of vitamin D deficiency/insufficiency; however, some studies suggest that supplementation with 50,000 units ergocalciferol (vitamin D2) weekly for 8 weeks, followed by subsequent dosing of 50,000 units every 2 to 4 weeks thereafter, is effective at restoring and maintaining adequate vitamin D levels.11 Clearly, vitamin D deficiency is a common, fixable risk factor for osteoporosis and its complications. This study aimed to evaluate the awareness and treatment of vitamin D deficiency/insufficiency in an extended care population in a single Veterans Health Administration (VHA) hospital. The primary purposes of this paper were to (1) characterize vitamin D evaluation in the ECC; (2) determine the frequency of vitamin D deficiency/insufficiency among monitored patients; and (3) assess the treatment and follow-up that occurs when patients are identified to have low vitamin D levels.
than 65 years old, hemodialysis patients, and patients with history of parathyroidectomy were excluded. All ECC patients meeting inclusion criteria with documented vitamin D levels during the specified time period were evaluated. This research protocol was approved by the institutional review board (IRB), and a waiver for written consent was obtained from the IRB. Patients’ medical records were reviewed from the date of vitamin D level measurement until 12 months later to assess the following: serum 25(OH)D level, vitamin D therapy regimen if applicable (formulation, dose, frequency, duration of treatment), length of time to follow-up after initiation of vitamin D therapy, and posttreatment vitamin D level. We also collected information on confirmed diagnosis of osteoporosis, documented adverse events to vitamin D therapy (hypercalcemia, hyperphosphatemia), use of medications that may affect metabolism of vitamin D (phenytoin, carbamazepine, phenobarbital, theophylline, rifampin, and isoniazid), and documentation of fall or fracture occurring posttreatment. We analyzed whether patients were receiving appropriate or inappropriate treatment using the following criteria: any formulation of vitamin D was considered suitable in patients with vitamin D insufficiency. Vitamin D–deficient patients require high doses of vitamin D; therefore, only ergocalciferol 50,000 units or calcitriol were considered adequate treatment in these patients. Cholecalciferol 50,000-unit capsules were not on the market during the period of this study; thus treatment with cholecalciferol at doses available at our facility (400 units) was considered insufficient therapy for patients with vitamin D deficiency. Currently available formulations of vitamin D are listed in Table 1. All patients receiving vitamin D therapy should also receive calcium supplementation. We examined whether or not patients were receiving calcium, although we did not evaluate the appropriateness of the dose. Finally, treatment of vitamin D insufficiency/deficiency was deemed appropriate only if a patient had a repeat vitamin D measurement within 3 months of beginning vitamin D therapy. Data analysis was performed using descriptive statistics. Counts and percentages were used to summarize categorical variables. In addition, we estimated the rate of vitamin D insufficiency and deficiency in the population.
METHODS A list of veterans residing in the ECC between January 1, 2001, and December 31, 2006, was extracted from the computerized patient record system (CPRS). All ECC patients during this time period were screened for inclusion; patients younger Table 1.
RESULTS There were 2218 unique admissions to the ECC between January 1, 2001, and December 31, 2006 (Figure 1). A total of 229 patients (10%) had at least one serum vitamin D
Available Vitamin D Formulations
Formulation
Available as
Cholecalciferol (vitamin D3) Ergocalciferol (vitamin D2)
Tablets: 400IU, 1000IU,* 5000IU,* 50,000 IU* Capsules: 400IU, 50,000IU Oral solution: 8000 units/mL Capsules: 0.25 mcg, 0.5 mcg Oral solution: 1 mg/mL Injectable solution: 1 mg/mL
Calcitriol (1,25-dihydroxyvitamin D)†
* Not available on the VA National Formulary. † Physiologically active form of vitamin D; treatment of choice for patients with renal failure. 654 Braddy et al
JAMDA – November 2009
Unique admissions to ECC 1/1/01 – 12/31/06 n=2218
Vitamin D level n=229 (10%)
No vitamin D level n=1989 (90%)
Met inclusion criteria n=164 (72%)
Low vitamin D level n=83 (51%)
Deficient vitamin D n=60 (72%)
Sufficient vitamin D level n=81 (49%)
Insufficient vitamin D n=23 (28%)
Fig. 1. Patient screening approach for inclusion into study.
measurement; 90% of patients did not have a serum vitamin D level measured. Seventy-two percent of patients with a serum vitamin D level met inclusion criteria for the study (n 5 164). Patients who were younger than 65 and/or were receiving hemodialysis were excluded (n 5 65). Of those 164 patients meeting inclusion criteria, approximately half (n 5 83) had low vitamin D levels. Twenty-eight percent (n 5 23) of patients with low vitamin D levels were insufficient, whereas 72% (n 5 60) were deficient of vitamin D. Twenty-seven percent of patients (n 5 22) had a dual-energy x-ray absorptiometry (DEXA) score lower than –2.5 confirming a diagnosis of osteoporosis, whereas an additional 11 patients had osteoporosis listed as a diagnosis in their medical charts but did not have documented DEXA scans. Six percent (n 5 5) of patients were taking a medication that interferes with vitamin D metabolism. Demographic information for patients with low vitamin D status is shown in Table 2. Of patients with deficient/insufficient vitamin D levels, 69% received some form of vitamin D therapy with cholecalciferol, ergocalciferol, or calcitriol (Table 3). Thirty-one percent of patients received no treatment for vitamin D defi-
ciency/insufficiency. Eleven percent of treated patients received duplicate treatment with more than one form of vitamin D therapy simultaneously. Figure 2 shows a breakdown of vitamin D formulations prescribed in response to low vitamin D levels. We found no uniformity in the vitamin D treatment regimen prescribed (formulation, dose, dosing frequency, duration of therapy). Fewer than half of patients (43%) had a follow-up vitamin D level within 3 months after starting vitamin D therapy. Among patients who did have a repeat vitamin D level measured, posttreatment serum vitamin D levels ranged from less than 7.0 to 56 ng/mL. One of 57 patients receiving vitamin D therapy experienced an adverse reaction: 1 patient who received calcitriol 0.5 mg/day for a total duration of 17 weeks experienced an increase in serum calcium from 11.02 ng/ mL before treatment to 11.86 ng/mL after treatment. Of 60 patients with deficient vitamin D status, 22% received appropriate vitamin D therapy with ergocalciferol or calcitriol plus supplemental calcium. Ten percent received the aforementioned treatment and had a repeat vitamin D level within 3 months of beginning vitamin D therapy (Table
Table 2.
Table 3.
Study Participant Demographics
Mean age Gender Male Female Race White African American Asian Hispanic Not specified
ORIGINAL STUDIES
Different Modes of Vitamin D Therapy in this Study
77.8 years (range 65–94 years) 98.8% (n582) 0.2% (n51) 83.1% (n569) 12.1% (n510) 1.2% (n51) 1.2% (n51) 2.4% (n52)
n (%) Total583 Patients receiving any vitamin D therapy Patients NOT receiving vitamin D therapy Patients with follow-up vitamin D level Patients receiving duplicate vitamin D therapy
57 (69) 26 (31) 36 (43) 9 (11)
Braddy et al 655
Few studies have examined vitamin D status in elderly, male, long-term care patients. Our study revealed a very low frequency (10%) of vitamin D screening in our study population. In addition, among those patients in our predominantly male, long-term care, veteran population who had vitamin D levels assessed, our study found a high rate of vitamin D insufficiency and deficiency. The high prevalence of vitamin D deficiency among screened ECC residents is consistent with the results of a study in elderly ambulatory outpatients by Linnebur et al.12 This study, which defined vitamin D insufficiency as 25(OH)D concentrations lower than 32 ng/mL, found 74% of all participants and 51% of male participants to be vitamin Dinsufficient. Most patients in this study were female (68%), whereas our study population was almost exclusively male (99%). What is notable about the Linnebur et al. study is that most vitamin D–insufficient patients were taking at least 400 to 600 units/day of vitamin D, suggesting that these doses are inadequate to maintain sufficient vitamin D levels. Additional studies support the frequent need for adequate vitamin D supplementation among institutionalized elderly to maintain sufficient serum 25(OH)D levels. O’Dowd et al13 studied 109 elderly nursing home residents in the New York City area and found that 46% of participants taking cho-
lecalciferol 200 to 400 units/day were deficient of vitamin D (25[OH]D concentrations \15 ng/mL). In another small study assessing vitamin D deficiency in 35 residents of a VA Medical Center nursing home, the mean 25(OH)D level was 17.4 5.2 ng/mL.4 Overall, studies suggest the rate of vitamin D deficiency among community dwelling elderly men and women to be between 40% and 100%1. We can assume that vitamin D would be lowest in institutionalized elderly, as a result of poorer dietary intake, decreased sun exposure, and high rates of comorbidities, such as liver and renal disease. Unlike previous studies that described the baseline vitamin D supplementation of vitamin D–insufficient/deficient individuals, our study focused on assessing the response to low vitamin D levels, including treatments initiated and followup that occurred. Although the National Academy of Sciences recommends a daily vitamin D intake of 400 units/ day for people 51 to 70 years old and 600 units/day for people age 71 years and older to maintain adequate vitamin D levels, recent consensus in the literature suggests that individuals with vitamin D insufficiency will need at least 800 to 1000 units/day of vitamin D to achieve the target 25(OH)D level of 30 ng/mL. Furthermore, for patients with vitamin D deficiency, recent literature suggests that 50,000 units ergocalciferol (vitamin D2) weekly for 8 weeks, followed by subsequent dosing of 50,000 units every 2 to 4 weeks thereafter, is effective at restoring and maintaining adequate vitamin D levels.11 According to these newer recommendations, very few vitamin D–deficient patients in our study received adequate treatment, and follow-up was rare. Our results indicate that many patients (31%) received no vitamin D therapy at all following a low vitamin D level. Among patients with vitamin D insufficiency, 61% received some form of vitamin D supplementation with concurrent calcium supplementation, yet 78% did not have a follow-up vitamin D level to assess whether treatment was successful. In addition, 78% of deficient patients did not receive high-dose vitamin D supplementation necessary to restore vitamin D levels to normal along with calcium supplementation, and 90% did not have a repeat vitamin D level. Our results suggest several ways in which patient care can be improved. First, educating providers in the ECC about the high morbidity and mortality associated with osteoporosis in elderly males, as well as the essential role that vitamin D plays in bone health and muscle function, is a high priority. New reviews of published studies indicate that, in addition to improving bone mineral density, vitamin D supplementation also reduces falls and may reduce the risk of fracture. As a result, we believe all appropriate patients should have
Table 4. Patients
Table 5. Patients
11% 23%
Ergocalciferol Calcitriol 6%
31%
Cholecalciferol No treatment Ergo OR Calc + Cholecalc
29% Fig. 2. Vitamin D formulations prescribed in response to low Vitamin D levels.
4). Of 23 patients with insufficient vitamin D status, 61% received appropriate vitamin D therapy with ergocalciferol, calcitriol, or cholecalciferol plus supplemental calcium. Twenty-two percent received appropriate treatment along with a follow-up vitamin D level within 3 months of initiating vitamin D therapy (Table 5). DISCUSSION
Appropriateness of Vitamin D Therapy in Vitamin D–Deficient
Appropriateness of Vitamin D Therapy in Vitamin D–Insufficient
n (%) Total560 Ergocalciferol OR calcitriol1 calcium supplement Above treatment WITH repeat vitamin D level
656 Braddy et al
13 (22) 6 (10)
n (%) Total523 Ergocalciferol OR calcitriol OR cholecalciferol1calcium supplement Above treatment WITH repeat vitamin D level
14 (61) 5 (22)
JAMDA – November 2009
25(OH)D levels measured to identify those with low vitamin D status. Because institutionalized patients, as well as patients being evaluated for or with established osteoporosis, are considered appropriate candidates for screening of 25(OH)D levels, most of our long-term care population would benefit from screening. Furthermore, we promote the establishment of institution-wide guidelines consistent with recent literature for restoring normal vitamin D levels in patients with inadequate lab results. As previous studies indicate, supplementation with cholecalciferol up to 600 IU/day is not successful at restoring or maintaining adequate vitamin D levels in the elderly. Therefore, our goal should be to treat vitamin D–deficient patients with vitamin D 50,000 IU/week for at least 8 weeks, with subsequent dosing as described previously. Finally, in accord with the literature, follow-up vitamin D levels should be repeated approximately 3 months after initiating vitamin D therapy to assess patient response. As only 10% of patients residing in the ECC during the study period were monitored for vitamin D status, it is difficult to know whether the high prevalence of vitamin D deficiency we found among monitored patients is truly representative of the entire ECC population. Whether selected patients were chosen for monitoring based on certain characteristics or risk factors is unknown. However, as mentioned earlier, recent review articles indicate that all institutionalized elderly are candidates for vitamin D monitoring, therefore suggesting that monitoring in our long-term care facility is largely inadequate. Commercial assays typically measure total 25(OH)D, but some labs report 25(OH)D2 and 25(OH)D3 values separately. The laboratory tests the VA has used to assess vitamin D status have changed over the years, therefore we were unable to accurately differentiate the difference between insufficiency and deficiency in some patients. We did not exclude patients using medications that may interfere with vitamin D metabolism, such as anticonvulsants (although the percentage was very low [6%]), nor did we exclude patients with liver or renal disease (except those on hemodialysis) in order to ensure generalizability of our results to the entire ECC population. Moreover, these patients are most likely to have low vitamin D status, and thus are most in need of monitoring and, presumably, vitamin D supplementation. CONCLUSIONS Our study suggests that vitamin D insufficiency/deficiency is prevalent among elderly, institutionalized, predominantly male veterans in a VA hospital Extended Care Center. In addition, few patients in our study who were identified to have low vitamin D levels received adequate treatment and
ORIGINAL STUDIES
follow-up. Based on our findings and the known benefits of vitamin D repletion therapy for preventing falls and fracture, as well as the emerging benefits reported in studies of numerous other chronic illnesses, we recommend expanding screening of long-term care patients and ensuring appropriate treatment and follow-up to restore vitamin D levels to normal to help decrease morbidity associated with low vitamin D levels. ACKNOWLEDGMENTS We thank Nicholas Emanuele, MD, Professor and Division Director, Division of Endocrinology & Metabolism, Department of Medicine, Loyola University Health System for his review of this manuscript and suggestions. There are no conflicts of interest to report. REFERENCES 1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–281. 2. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477–501. 3. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353–373. 4. McMurtry CT, Young SE, Downs RW, Adler RA. Mild vitamin D deficiency and secondary hyperparathyroidism in nursing home patients receiving adequate dietary vitamin D. J Am Geriatr Soc 1992;40: 343–347. 5. Mosekilde L. Vitamin D and the elderly. Clin Endocrinol 2005;62: 265–281. 6. Miller E. Vitamin D insufficiency in male osteoporosis. Clin Cornerstone 2006;8:S14–S19. 7. Passeri G, Pini G, Troiano L, et al. Low vitamin D status, high bone turnover, and bone fractures in centenarians. J Clin Endocrinol Metab 2003; 88:5109–5115. 8. Simonelli C, Weiss TW, Morancey J, et al. Prevalence of vitamin D inadequacy in a minimal trauma fracture population. Curr Med Res Opin 2005;21:1069–1074. 9. Bischoff-Ferrarri HA, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004;291:1999–2006. 10. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. JAMA 2005;293:2257–2264. 11. Holick MF, Garabedian M. Vitamin D: Photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006. p. 129–137. 12. Linnebur SA, Vondracek SF, Vande Griend JP, et al. Prevalence of vitamin D insufficiency in elderly ambulatory outpatients in Denver, Colorado. Am J Geriatr Pharmacother 2007;5:1–8. 13. O’Dowd KJ, Clemens TL, Kelsey JL, Lindsay R. Exogenous calciferol (vitamin D) and vitamin D endocrine status among elderly nursing home residents in the New York City area. J Am Geriatr Soc 1993;41: 414–421.
Braddy et al 657
Objectives: To evaluate the prevalence of vitamin D deficiency/insufficiency in long-term care patients at a Veterans Health Administration (VHA) hospital and to assess treatment and follow-up of low vitamin D levels. Design: Observational cohort study.
of patients with low vitamin D levels received some form of vitamin D therapy, whereas 43% received treatment as well as follow-up evaluation of vitamin D status within 3 months. Only 13% received a formulation of vitamin D appropriate for the severity of their deficiency/insufficiency with concurrent calcium supplementation and had a repeat vitamin D level within 3 months.
Setting: VA hospital extended care center (ECC). Participants: 2218 ECC patients between January 2001 and December 2006 were screened. Measurement: Serum 25-hydroxyvitamin D (25[OH]D) level, vitamin D therapy regimen, time to follow-up, documented adverse event to vitamin D therapy. Results: Of 2218 patients admitted to the ECC during the study period, 229 (10%) had a vitamin D level measured. Among these 229 patients, 49% were vitamin D sufficient (25[OH]D $30 ng/mL), 14% were insufficient (25[OH]D 5 21–29 ng/mL), and 37% were deficient (25[OH]D #20 ng/mL). Sixty-nine percent
Vitamin D is a key factor influencing calcium and phosphorus homeostasis and bone health. Serum 25-hydroxyvitamin D (25[OH]D) is the vitamin D metabolite measured clinically to assess vitamin D status.1 Reference values for serum 25(OH)D are based on adverse health outcomes rather than population-based reference values, which vary based on geographical region, as well as lifestyle and environmental factors.2 Vitamin D deficiency is defined as 25(OH)D levels of 20 ng/mL or less, whereas levels between 21 and 29 ng/
Edward Hines, Jr. VA Hospital, Hines, IL (K.K.B., S.N.I., K.R.P., T.A.L.); VA Maryland Health Care System, Baltimore, MD (K.K.B.). Address correspondence to Kathryn K. Braddy, PharmD, VA Maryland Health Care System, 10 N. Greene Street (119), Baltimore, MD 21201. E-mail: kathryn. [email protected]
Published by Elsevier, Inc. on behalf of the American Medical Directors Association DOI:10.1016/j.jamda.2009.08.010 ORIGINAL STUDIES
Conclusion: Vitamin D levels were measured infrequently in long-term care patients. Among those monitored, the rate of vitamin D deficiency/insufficiency is high. Few patients with low vitamin D status received proper treatment and follow-up. These data support the need to educate physicians regarding the high prevalence of vitamin D insufficiency/deficiency among long-term care patients to ensure that patients with low vitamin D levels are identified and treated appropriately. (J Am Med Dir Assoc 2009; 10: 653–657) Keywords: Vitamin D; long-term care; vitamin D insufficiency; vitamin D deficiency
mL are deemed insufficient; 25(OH)D levels 30 ng/mL or higher are considered sufficient.1 Vitamin D deficiency/insufficiency is a widespread problem in the elderly, particularly in institutionalized and geriatric populations. The prevalence of vitamin D deficiency is estimated at 41% in outpatients aged 49 to 83 years,3 and although there are no definitive estimates of the prevalence of vitamin D deficiency in nursing home patients, studies indicate that 25(OH)D levels are significantly lower in nursing home patients compared with community-dwelling elderly.4 The main sources of vitamin D are exposure to sunlight and limited dietary sources, such as fatty fish and egg yolks, and certain fortified foods3. Vitamin D levels decline as a result of multiple factors associated with aging, including decreased solar exposure, decreased dietary intake of vitamin D, and decreased dermal production of vitamin D, as well as decreased conversion of vitamin D to its active form by the kidneys owing to age-related decline in renal function.5 Braddy et al 653
Low serum vitamin D leads to impaired calcium metabolism, in turn triggering secondary hyperparathyroidism, increased bone turnover, and progressive bone loss.3 Osteoporosis is a leading cause of morbidity and mortality in the elderly, although largely undetected in men. Males who suffer osteoporotic fracture, however, have a worse prognosis than age-matched females.6 In patients with osteoporosis and/or fracture, the prevalence of low vitamin D levels appears to be even higher than in the general population; 76% of osteoporotic patients had very low vitamin D levels in a study conducted by Passeri et al,7 and Simonelli et al8 reported that 97% of patients in a study of patients 50 years and older hospitalized for nontraumatic fracture had 25(OH)D levels lower than 30 ng/mL. Furthermore, recent meta-analyses of randomized controlled trials concluded that vitamin D supplementation appears to reduce the risk of falls and fractures among older individuals.9,10 Vitamin D is an important factor in optimal muscle strength and function. Ongoing research also suggests benefits of vitamin D supplementation in several other chronic illnesses, including many cancers, autoimmune diseases, infectious diseases, cardiovascular disease, and possibly psychiatric illnesses such as depression and schizophrenia. Prior research has shown that vitamin D supplementation can reverse the negative effects of hypovitaminosis D on bone mineral density. Currently, there are no consensus guidelines on proper treatment of vitamin D deficiency/insufficiency; however, some studies suggest that supplementation with 50,000 units ergocalciferol (vitamin D2) weekly for 8 weeks, followed by subsequent dosing of 50,000 units every 2 to 4 weeks thereafter, is effective at restoring and maintaining adequate vitamin D levels.11 Clearly, vitamin D deficiency is a common, fixable risk factor for osteoporosis and its complications. This study aimed to evaluate the awareness and treatment of vitamin D deficiency/insufficiency in an extended care population in a single Veterans Health Administration (VHA) hospital. The primary purposes of this paper were to (1) characterize vitamin D evaluation in the ECC; (2) determine the frequency of vitamin D deficiency/insufficiency among monitored patients; and (3) assess the treatment and follow-up that occurs when patients are identified to have low vitamin D levels.
than 65 years old, hemodialysis patients, and patients with history of parathyroidectomy were excluded. All ECC patients meeting inclusion criteria with documented vitamin D levels during the specified time period were evaluated. This research protocol was approved by the institutional review board (IRB), and a waiver for written consent was obtained from the IRB. Patients’ medical records were reviewed from the date of vitamin D level measurement until 12 months later to assess the following: serum 25(OH)D level, vitamin D therapy regimen if applicable (formulation, dose, frequency, duration of treatment), length of time to follow-up after initiation of vitamin D therapy, and posttreatment vitamin D level. We also collected information on confirmed diagnosis of osteoporosis, documented adverse events to vitamin D therapy (hypercalcemia, hyperphosphatemia), use of medications that may affect metabolism of vitamin D (phenytoin, carbamazepine, phenobarbital, theophylline, rifampin, and isoniazid), and documentation of fall or fracture occurring posttreatment. We analyzed whether patients were receiving appropriate or inappropriate treatment using the following criteria: any formulation of vitamin D was considered suitable in patients with vitamin D insufficiency. Vitamin D–deficient patients require high doses of vitamin D; therefore, only ergocalciferol 50,000 units or calcitriol were considered adequate treatment in these patients. Cholecalciferol 50,000-unit capsules were not on the market during the period of this study; thus treatment with cholecalciferol at doses available at our facility (400 units) was considered insufficient therapy for patients with vitamin D deficiency. Currently available formulations of vitamin D are listed in Table 1. All patients receiving vitamin D therapy should also receive calcium supplementation. We examined whether or not patients were receiving calcium, although we did not evaluate the appropriateness of the dose. Finally, treatment of vitamin D insufficiency/deficiency was deemed appropriate only if a patient had a repeat vitamin D measurement within 3 months of beginning vitamin D therapy. Data analysis was performed using descriptive statistics. Counts and percentages were used to summarize categorical variables. In addition, we estimated the rate of vitamin D insufficiency and deficiency in the population.
METHODS A list of veterans residing in the ECC between January 1, 2001, and December 31, 2006, was extracted from the computerized patient record system (CPRS). All ECC patients during this time period were screened for inclusion; patients younger Table 1.
RESULTS There were 2218 unique admissions to the ECC between January 1, 2001, and December 31, 2006 (Figure 1). A total of 229 patients (10%) had at least one serum vitamin D
Available Vitamin D Formulations
Formulation
Available as
Cholecalciferol (vitamin D3) Ergocalciferol (vitamin D2)
Tablets: 400IU, 1000IU,* 5000IU,* 50,000 IU* Capsules: 400IU, 50,000IU Oral solution: 8000 units/mL Capsules: 0.25 mcg, 0.5 mcg Oral solution: 1 mg/mL Injectable solution: 1 mg/mL
Calcitriol (1,25-dihydroxyvitamin D)†
* Not available on the VA National Formulary. † Physiologically active form of vitamin D; treatment of choice for patients with renal failure. 654 Braddy et al
JAMDA – November 2009
Unique admissions to ECC 1/1/01 – 12/31/06 n=2218
Vitamin D level n=229 (10%)
No vitamin D level n=1989 (90%)
Met inclusion criteria n=164 (72%)
Low vitamin D level n=83 (51%)
Deficient vitamin D n=60 (72%)
Sufficient vitamin D level n=81 (49%)
Insufficient vitamin D n=23 (28%)
Fig. 1. Patient screening approach for inclusion into study.
measurement; 90% of patients did not have a serum vitamin D level measured. Seventy-two percent of patients with a serum vitamin D level met inclusion criteria for the study (n 5 164). Patients who were younger than 65 and/or were receiving hemodialysis were excluded (n 5 65). Of those 164 patients meeting inclusion criteria, approximately half (n 5 83) had low vitamin D levels. Twenty-eight percent (n 5 23) of patients with low vitamin D levels were insufficient, whereas 72% (n 5 60) were deficient of vitamin D. Twenty-seven percent of patients (n 5 22) had a dual-energy x-ray absorptiometry (DEXA) score lower than –2.5 confirming a diagnosis of osteoporosis, whereas an additional 11 patients had osteoporosis listed as a diagnosis in their medical charts but did not have documented DEXA scans. Six percent (n 5 5) of patients were taking a medication that interferes with vitamin D metabolism. Demographic information for patients with low vitamin D status is shown in Table 2. Of patients with deficient/insufficient vitamin D levels, 69% received some form of vitamin D therapy with cholecalciferol, ergocalciferol, or calcitriol (Table 3). Thirty-one percent of patients received no treatment for vitamin D defi-
ciency/insufficiency. Eleven percent of treated patients received duplicate treatment with more than one form of vitamin D therapy simultaneously. Figure 2 shows a breakdown of vitamin D formulations prescribed in response to low vitamin D levels. We found no uniformity in the vitamin D treatment regimen prescribed (formulation, dose, dosing frequency, duration of therapy). Fewer than half of patients (43%) had a follow-up vitamin D level within 3 months after starting vitamin D therapy. Among patients who did have a repeat vitamin D level measured, posttreatment serum vitamin D levels ranged from less than 7.0 to 56 ng/mL. One of 57 patients receiving vitamin D therapy experienced an adverse reaction: 1 patient who received calcitriol 0.5 mg/day for a total duration of 17 weeks experienced an increase in serum calcium from 11.02 ng/ mL before treatment to 11.86 ng/mL after treatment. Of 60 patients with deficient vitamin D status, 22% received appropriate vitamin D therapy with ergocalciferol or calcitriol plus supplemental calcium. Ten percent received the aforementioned treatment and had a repeat vitamin D level within 3 months of beginning vitamin D therapy (Table
Table 2.
Table 3.
Study Participant Demographics
Mean age Gender Male Female Race White African American Asian Hispanic Not specified
ORIGINAL STUDIES
Different Modes of Vitamin D Therapy in this Study
77.8 years (range 65–94 years) 98.8% (n582) 0.2% (n51) 83.1% (n569) 12.1% (n510) 1.2% (n51) 1.2% (n51) 2.4% (n52)
n (%) Total583 Patients receiving any vitamin D therapy Patients NOT receiving vitamin D therapy Patients with follow-up vitamin D level Patients receiving duplicate vitamin D therapy
57 (69) 26 (31) 36 (43) 9 (11)
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Few studies have examined vitamin D status in elderly, male, long-term care patients. Our study revealed a very low frequency (10%) of vitamin D screening in our study population. In addition, among those patients in our predominantly male, long-term care, veteran population who had vitamin D levels assessed, our study found a high rate of vitamin D insufficiency and deficiency. The high prevalence of vitamin D deficiency among screened ECC residents is consistent with the results of a study in elderly ambulatory outpatients by Linnebur et al.12 This study, which defined vitamin D insufficiency as 25(OH)D concentrations lower than 32 ng/mL, found 74% of all participants and 51% of male participants to be vitamin Dinsufficient. Most patients in this study were female (68%), whereas our study population was almost exclusively male (99%). What is notable about the Linnebur et al. study is that most vitamin D–insufficient patients were taking at least 400 to 600 units/day of vitamin D, suggesting that these doses are inadequate to maintain sufficient vitamin D levels. Additional studies support the frequent need for adequate vitamin D supplementation among institutionalized elderly to maintain sufficient serum 25(OH)D levels. O’Dowd et al13 studied 109 elderly nursing home residents in the New York City area and found that 46% of participants taking cho-
lecalciferol 200 to 400 units/day were deficient of vitamin D (25[OH]D concentrations \15 ng/mL). In another small study assessing vitamin D deficiency in 35 residents of a VA Medical Center nursing home, the mean 25(OH)D level was 17.4 5.2 ng/mL.4 Overall, studies suggest the rate of vitamin D deficiency among community dwelling elderly men and women to be between 40% and 100%1. We can assume that vitamin D would be lowest in institutionalized elderly, as a result of poorer dietary intake, decreased sun exposure, and high rates of comorbidities, such as liver and renal disease. Unlike previous studies that described the baseline vitamin D supplementation of vitamin D–insufficient/deficient individuals, our study focused on assessing the response to low vitamin D levels, including treatments initiated and followup that occurred. Although the National Academy of Sciences recommends a daily vitamin D intake of 400 units/ day for people 51 to 70 years old and 600 units/day for people age 71 years and older to maintain adequate vitamin D levels, recent consensus in the literature suggests that individuals with vitamin D insufficiency will need at least 800 to 1000 units/day of vitamin D to achieve the target 25(OH)D level of 30 ng/mL. Furthermore, for patients with vitamin D deficiency, recent literature suggests that 50,000 units ergocalciferol (vitamin D2) weekly for 8 weeks, followed by subsequent dosing of 50,000 units every 2 to 4 weeks thereafter, is effective at restoring and maintaining adequate vitamin D levels.11 According to these newer recommendations, very few vitamin D–deficient patients in our study received adequate treatment, and follow-up was rare. Our results indicate that many patients (31%) received no vitamin D therapy at all following a low vitamin D level. Among patients with vitamin D insufficiency, 61% received some form of vitamin D supplementation with concurrent calcium supplementation, yet 78% did not have a follow-up vitamin D level to assess whether treatment was successful. In addition, 78% of deficient patients did not receive high-dose vitamin D supplementation necessary to restore vitamin D levels to normal along with calcium supplementation, and 90% did not have a repeat vitamin D level. Our results suggest several ways in which patient care can be improved. First, educating providers in the ECC about the high morbidity and mortality associated with osteoporosis in elderly males, as well as the essential role that vitamin D plays in bone health and muscle function, is a high priority. New reviews of published studies indicate that, in addition to improving bone mineral density, vitamin D supplementation also reduces falls and may reduce the risk of fracture. As a result, we believe all appropriate patients should have
Table 4. Patients
Table 5. Patients
11% 23%
Ergocalciferol Calcitriol 6%
31%
Cholecalciferol No treatment Ergo OR Calc + Cholecalc
29% Fig. 2. Vitamin D formulations prescribed in response to low Vitamin D levels.
4). Of 23 patients with insufficient vitamin D status, 61% received appropriate vitamin D therapy with ergocalciferol, calcitriol, or cholecalciferol plus supplemental calcium. Twenty-two percent received appropriate treatment along with a follow-up vitamin D level within 3 months of initiating vitamin D therapy (Table 5). DISCUSSION
Appropriateness of Vitamin D Therapy in Vitamin D–Deficient
Appropriateness of Vitamin D Therapy in Vitamin D–Insufficient
n (%) Total560 Ergocalciferol OR calcitriol1 calcium supplement Above treatment WITH repeat vitamin D level
656 Braddy et al
13 (22) 6 (10)
n (%) Total523 Ergocalciferol OR calcitriol OR cholecalciferol1calcium supplement Above treatment WITH repeat vitamin D level
14 (61) 5 (22)
JAMDA – November 2009
25(OH)D levels measured to identify those with low vitamin D status. Because institutionalized patients, as well as patients being evaluated for or with established osteoporosis, are considered appropriate candidates for screening of 25(OH)D levels, most of our long-term care population would benefit from screening. Furthermore, we promote the establishment of institution-wide guidelines consistent with recent literature for restoring normal vitamin D levels in patients with inadequate lab results. As previous studies indicate, supplementation with cholecalciferol up to 600 IU/day is not successful at restoring or maintaining adequate vitamin D levels in the elderly. Therefore, our goal should be to treat vitamin D–deficient patients with vitamin D 50,000 IU/week for at least 8 weeks, with subsequent dosing as described previously. Finally, in accord with the literature, follow-up vitamin D levels should be repeated approximately 3 months after initiating vitamin D therapy to assess patient response. As only 10% of patients residing in the ECC during the study period were monitored for vitamin D status, it is difficult to know whether the high prevalence of vitamin D deficiency we found among monitored patients is truly representative of the entire ECC population. Whether selected patients were chosen for monitoring based on certain characteristics or risk factors is unknown. However, as mentioned earlier, recent review articles indicate that all institutionalized elderly are candidates for vitamin D monitoring, therefore suggesting that monitoring in our long-term care facility is largely inadequate. Commercial assays typically measure total 25(OH)D, but some labs report 25(OH)D2 and 25(OH)D3 values separately. The laboratory tests the VA has used to assess vitamin D status have changed over the years, therefore we were unable to accurately differentiate the difference between insufficiency and deficiency in some patients. We did not exclude patients using medications that may interfere with vitamin D metabolism, such as anticonvulsants (although the percentage was very low [6%]), nor did we exclude patients with liver or renal disease (except those on hemodialysis) in order to ensure generalizability of our results to the entire ECC population. Moreover, these patients are most likely to have low vitamin D status, and thus are most in need of monitoring and, presumably, vitamin D supplementation. CONCLUSIONS Our study suggests that vitamin D insufficiency/deficiency is prevalent among elderly, institutionalized, predominantly male veterans in a VA hospital Extended Care Center. In addition, few patients in our study who were identified to have low vitamin D levels received adequate treatment and
ORIGINAL STUDIES
follow-up. Based on our findings and the known benefits of vitamin D repletion therapy for preventing falls and fracture, as well as the emerging benefits reported in studies of numerous other chronic illnesses, we recommend expanding screening of long-term care patients and ensuring appropriate treatment and follow-up to restore vitamin D levels to normal to help decrease morbidity associated with low vitamin D levels. ACKNOWLEDGMENTS We thank Nicholas Emanuele, MD, Professor and Division Director, Division of Endocrinology & Metabolism, Department of Medicine, Loyola University Health System for his review of this manuscript and suggestions. There are no conflicts of interest to report. REFERENCES 1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–281. 2. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477–501. 3. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353–373. 4. McMurtry CT, Young SE, Downs RW, Adler RA. Mild vitamin D deficiency and secondary hyperparathyroidism in nursing home patients receiving adequate dietary vitamin D. J Am Geriatr Soc 1992;40: 343–347. 5. Mosekilde L. Vitamin D and the elderly. Clin Endocrinol 2005;62: 265–281. 6. Miller E. Vitamin D insufficiency in male osteoporosis. Clin Cornerstone 2006;8:S14–S19. 7. Passeri G, Pini G, Troiano L, et al. Low vitamin D status, high bone turnover, and bone fractures in centenarians. J Clin Endocrinol Metab 2003; 88:5109–5115. 8. Simonelli C, Weiss TW, Morancey J, et al. Prevalence of vitamin D inadequacy in a minimal trauma fracture population. Curr Med Res Opin 2005;21:1069–1074. 9. Bischoff-Ferrarri HA, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004;291:1999–2006. 10. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. JAMA 2005;293:2257–2264. 11. Holick MF, Garabedian M. Vitamin D: Photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006. p. 129–137. 12. Linnebur SA, Vondracek SF, Vande Griend JP, et al. Prevalence of vitamin D insufficiency in elderly ambulatory outpatients in Denver, Colorado. Am J Geriatr Pharmacother 2007;5:1–8. 13. O’Dowd KJ, Clemens TL, Kelsey JL, Lindsay R. Exogenous calciferol (vitamin D) and vitamin D endocrine status among elderly nursing home residents in the New York City area. J Am Geriatr Soc 1993;41: 414–421.
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