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Vitamin D: Beneficial for Pain, Fracture, and Falls in Long-Term Care Residents?
Vitamin D deficiency is common in elderly individuals, including long-term care (LTC) residents. Supplementation with vitamin D has been reported to ameliorate chronic pain and reduce the incidence of falls in these persons. It has also been associated with reduced mortality following a fracture. However, many studies assessing have been small or retrospective, and there is currently no consensus on optimal dosing of vitamin D, or on the role of adding calcium or other therapies such as antiosteoporotic drugs to vitamin D therapy. Despite these limitations, current evidence suggests that the vitamin D risk-to-benefit ratio is favorable and cost-effectiveness may be exceptional, particularly for LTC residents found to be vitamin D deficient or insufficient. The authors review sources of vitamin D, target levels and dosing strategies, and the use of vitamin D to treat chronic musculoskeletal pain, reduce the risk of falls, and decrease the risk of mortality following a fracture. They also make recommendations for LTC residents based on currently available data. (Annals of Long-Term Care: Clinical Care and Aging. 19[5]:33-36.)
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Vitamin D is a fat-soluble prohormone that plays a major role in calcium regulation and bone development. It can be obtained through exposure to the sun or derived from ingested foods or supplements, but regardless of how it is acquired, it must be converted in the body to an active form. Although almost all adults older than 65 years should be supplementing with some form of vitamin D, many elderly individuals, including residents of long-term care (LTC) facilities, remain vitamin D deficient or insufficient. In 2003, Elliott and colleagues1 reported that 60% of 49 female residents of a Wisconsin nursing home had vitamin D levels low enough to cause secondary hyperparathyroidism, and only 4% of this population had normal vitamin D levels (>30 ng/mL). Braddy and colleagues2 reported similar findings in 2009 in both male and female patients. Of the 229 VA hospital extended care center patients who had their vitamin D levels measured in this study, 14% had insufficient 25-hydroxyvitamin D levels [25(OH)D], 21-29 ng/mL) and 37% were classified as deficient (25(OH)D, ≤20 ng/mL).
Low vitamin D levels have been associated with numerous maladies, including exacerbation of chronic musculoskeletal pain, increased risk of falls, and increased risk of mortality following a fracture. Although the benefits of vitamin D are widely recognized, there is currently no gold-standard method for replacement.3 We review the forms and sources of vitamin D, target levels and dosing strategies, and the use of vitamin D to treat chronic musculoskeletal pain, reduce the risk of falls, and decrease the risk of mortality following a fracture. We also make a few recommendations for LTC residents based on our assessment of current data.
Forms and Sources of Vitamin D
The two major forms of vitamin D are D2, or ergocalciferol, and D3, cholecalciferol. When people talk about vitamin D, they are typically referring to cholecalciferol, which is the naturally occurring form of vitamin D in humans. Cholecalciferol is obtained through exposure to the sun or from food sources, particularly animal-based products. Most over-the-counter supplements also take this form.4 Ergocalciferol is a plant-derived form of vitamin D, which is found in yeast and fungi, and is generally available through prescription, but it is also be found in some over-the-counter supplements and fortified foods.
After exposure to the sun’s ultraviolet B radiation, cholecalciferol is synthesized in the vitamin D receptors in the skin. Although most tissues in the human body express these receptors, making it possible to spend as little as 10 minutes in the sun to prevent deficiencies,5,6 a various of factors can affect UV radiation exposure and, subsequently, the amount of vitamin D that is synthesized. Factors to consider include season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen use.7
Vitamin D can also be obtained through food and nutritional supplements; however, few foods contain adequate amounts. The flesh of fish (eg, salmon, tuna, mackerel) and fish liver oils are the best sources.8 Smaller amounts can be found in beef liver, cheese, egg yolks, and mushrooms. Fortified foods provide most of the vitamin D in the American diet. In the United States, almost all milk is fortified to contain 100 IU of vitamin D per cup, accounting for 25% of the daily value or 50% of the adequate intake for individuals 14 to 50 years of age. Cereal flours, fruit juices, and milk-based products can also be fortified with vitamin D.9
Vitamin D2 from diet and vitamin D3 from diet and sun exposure undergo two hydroxylation reactions to produce an active form. They are first metabolized in the liver to produce 25-hydroxyvitamin D (25(OH)D), the major circulating form of vitamin D. This form is then taken up by renal proximal tubule epithelial cells via megalin-dependent endocytosis, producing 1,25-dihydroxyvitamin D (1,25(OH)12D), also known as calcitriol.10
Target Levels of Vitamin D and Dosing
Target levels of vitamin D and dosing in elderly LTC residents have not been specifically defined. The Institute for Clinical Systems Improvement guidelines from 2008 suggest a target level of at least 30 ng/mL,11 but the Vitamin D Council recommends a level between 50 and 80 ng/mL.4 Persons with vitamin D deficiency or insufficiency should have their vitamin D levels restored to at least 30 ng/mL before starting on maintenance doses, to keep stored and circulating vitamin D at appropriate levels.
Data on how to optimally dose vitamin D to correct deficiencies also conflict. For patients who do not have renal compromise, some experts recommend supplementing with 50,000 units of vitamin D2 weekly for 8 weeks, with a maintenance combination supplement of calcium plus vitamin D2 taken twice daily thereafter, and then periodically monitoring vitamin D levels.12 A maximum maintenance dose of 2000 IU daily is recommended by the Food and Nutrition Board; however, a monthly dose of 50,000 IU orally is often used to maintain vitamin D levels because this dosage can be covered by Medicare Part D prescription drug plans.8
Patients who are healthy and have no vitamin D deficiency should continue to have their 25(OH)D level periodically measured and, if necessary, take supplements to ensure that levels between 50 and 80 ng/mL are maintained year-round.4 Patients receiving high doses of vitamin D to correct deficiency should also undergo regular assessments of their vitamin D levels, as 25(OH)D levels that are consistently between 150 ng/mL and 200 ng/mL are potentially toxic and may lead to hypercalcemia and hyperphosphatemia.9
Vitamin D Therapy for Chronic Musculoskeletal Pain
Low-dose vitamin D has been used to treat chronic musculoskeletal pain. The proposed mechanism is that inadequate levels of vitamin D can cause hypocalcemia, which elevates parathyroid hormone (PTH) levels. The increase in PTH may lead to diminished bone mineral density (BMD), or osteopenia, and eventually to osteoporosis. In addition to diminished BMD, increased PTH levels produce negative changes in bone architecture and mineralization. The bone becomes a porous matrix that absorbs fluid, expanding and compressing the outer layers of periosteal tissues, which are replete with sensory pain fibers. The pain that results from this compression usually does not respond well to opioid and nonsteroidal anti-inflammatory medications.5,13
In a review of 22 clinical investigations (>3600 patients), Leavitt13 found that patients with pain were significantly more likely to be vitamin D deficient. Based on this finding, Leavitt concluded that “as a whole, the research evidence supports vitamin D supplementation as a potentially important therapy for helping to ameliorate chronic nonspecific musculoskeletal pain and fatigue syndromes.”
In contrast, a 2010 intervention review published in the Cochrane Library by Straube and colleagues,5 conducted a literature search of Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database, and concluded that the evidence for vitamin D use in chronic pain is “poor.” The authors found low-quality studies and an insufficient number of randomized controlled trials.
Although there is currently not enough evidence to support the use of vitamin D supplements to treat chronic pain and more research is needed to determine potential target groups, dosing strategies, and duration of therapy, any deficiency or insufficiency in vitamin D levels should be corrected. While restoring vitamin D levels may or may not have an impact on a patient’s pain, vitamin D is important in maintaining general health.
Vitamin D for Postfracture Treatment and Fall Reduction
The majority of available studies regarding postfracture treatment include calcium plus vitamin D interventions, rather than vitamin D therapy alone. Several studies have shown a correlation between calcium plus vitamin D supplementation and reduced mortality following a fracture. However, in one such study,14 which included 221 patients with hip fractures, the investigators found that supplementation with calcium plus vitamin D ranked only fourth among the variables that best explained post fracture survival. Age younger than 80 years, American Society of Anesthesiologists Physical Status class 1 to 2, and use of antiosteoporotic drugs in combination with calcium and vitamin D were better predictors of survival, ranking first, second, and third, respectively. Nevertheless, because excess mortality was highest among individuals who did not use antiosteoporotic drugs or calcium plus vitamin D, the authors speculated that there is a potential relationship between reduced mortality and calcium plus vitamin D use, but conceded that more studies are needed to determine a true association.14
In 2003, Latham and associates18 conducted a systematic review of 13 studies examining the effects of vitamin D supplementation on fall risk in older persons. Most of the trials reviewed had methodological problems, including a high risk of type II error because they were small and limited to ambulatory populations. Of the 13 trials, 10 showed no effect on falls or physical function; however, the 3 trials that used combination therapy with calcium documented a positive effect on the incidence of falls. Latham and associates calculated that the overall relative risk for fall reduction was 0.99 (95% confidence interval, 0.89-1.11), which was not statistically significant. Based on this finding, the authors concluded that there was insufficient evidence that vitamin D alone is beneficial and that larger better controlled studies are needed.
In 2008, LeBoff and associates15 assessed whether vitamin D levels affected the risk of falls in 110 women with hip fractures. Lower extremity gain scale (LEGS) was measured at 2, 6, and 12 months in a subset of women to gauge their lower extremity function. The investigators found that 25(OH)D levels were deficient (<32 ng/mL) in 96% of the patients, with 38% having extremely low levels (≤9 ng/mL). One year after the fracture, those with a 25(OH)D level of ≤9 ng/mL had poorer LEGS performance (P < .0001) and higher fall rates compared with those who had a level >9 ng/mL, with falls occurring in 51.5% versus 30.0%, respectively (P = .049); these findings were independent of grip strength or balance.
Despite the prevailing data that correcting or preventing vitamin D deficiency may reduce fracture risk, <29% of subjects with hip fractures are treated with calcium and vitamin D.16,17 Vitamin D deficiency causes muscle weakness, which could lead to falls. Although vitamin D supplementation may improve muscle strength, thereby reducing falls related to muscle weakness, it is not reasonable to expect vitamin D alone to change mobility problems that are related to other conditions. Vitamin D supplementation may be of benefit only in patients with seriously deficient levels of vitamin D.
A concern with some studies assessing the impact of vitamin D supplementation on fall reduction is that vitamin D dosing may have been inadequate to produce benefit. In addition, the amount and role of calcium supplementation and of antiosteoporotic therapies are variables that likely affect outcomes and require further assessment in studies of fracture treatment and fall reduction.
Recommendations for LTC Patients
Vitamin D has many associated and confirmed health benefits, especially in older adults. Based on the extremely low cost of vitamin D supplements, available evidence, and the relatively low rate and severity of toxicity issues, all residents of LTC facilities should be checked for vitamin D deficiency or insufficiency. Even residents who are found to have adequate levels of vitamin D may benefit from supplementing with 800 IU to 2000 IU of vitamin D daily. The goal should be to maintain vitamin D levels at least 30 ng/mL.12 For residents at risk of osteoporosis, falls, and fractures, consideration should be given to assuring adequate calcium intake, use of or antiosteoporotic therapy, or both, in addition to vitamin D supplementation.
Conclusion
A multitude of smaller studies and epidemiological reports have demonstrated benefits with vitamin D use, but large, prospective, well-designed studies are needed to confirm the long-term benefits and assess for risks in LTC residents. Because most current evidence suggests that the risk-to-benefit ratio of vitamin D use is favorable and cost-effectiveness may be exceptional, particularly for LTC residents who are found to be vitamin D deficient or insufficient, supplementation should be considered in these patients.
The authors report no relevant financial relationships.
Ms. Papas is a doctor of pharmacy candidate and Dr. Cluxton is professor of pharmacy practice & family medicine, The James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH.
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