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AAOS Now / Issue: May 2024 / commentary01

Alexandra E. Page, MD, FAAOS

AAOS Now

Published 5/29/2024
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Alexandra E. Page, MD, FAAOS
Commentary Clinical

It’s D-Lightful, D-Licious, D-Lovely: It’s D-Vitamin

Is vitamin D superhero or superhype?

With apologies to Cole Porter, “I feel a sudden urge to sing, the kind of ditty that invokes the …” virtues of vitamin D! Is vitamin D the miracle cure-all of the 21st century? One of the few advantages of aging is that I anticipate never taking another test on vitamin D metabolism. On the flip side, I regrettably seem to be more aware of my own aches and pains. When headlines started appearing over a decade ago, I dutifully placed a bottle of vitamin D on the shelf for daily consumption and sat back to await the return of my youth.

Vitamin D in the musculoskeletal system and beyond
In adults, the list of musculoskeletal (MSK) diagnoses impacted by vitamin D deficiency streams long. Associations between vitamin D deficiency and fragility fracture have been long-standing, but associations with soft-tissue injury and surgical treatment have been more recently reported. Higher index rates and re-injury after surgical reconstruction have been found for anterior cruciate ligament tears as well as patellar instability. Charcot arthropathy, rotator cuff repair complications, and prosthetic joint infection have been associated with hypovitaminosis D. The presence of a vitamin D receptor on skeletal muscle is the purported mechanism for increased strength metrics with supplementation. Another study found reduced rates of sports injury and improved performance with higher levels of vitamin D. In some of these studies, supplementation with vitamin D was done even absent deficiency or insufficiency of serum levels.

My fascination with vitamin D was really piqued when I became aware of its seemingly magical powers beyond the MSK realm. In an era when anti-inflammatory diets are the rage, vitamin D repletion has been demonstrated to reduce elevated C-reactive protein levels. Vitamin D acts as an immunomodulatory hormone, and a large level 1 study demonstrated a cumulative 22 percent reduction in incidence of autoimmune diseases in the 2,000 IU/day supplement arm over placebo. When the cohort was reassessed 2 years after cessation of supplementation, the protective effect had disappeared.

In recent years, deficiency has been associated with multiple autoimmune and inflammatory conditions. The short list includes cancer, diabetes, cardiovascular disease, inflammatory bowel disease, obesity, depression, and other neuro-psychiatric diseases. It has even been included among risk factors for early-onset dementia. Supplementation has been used to reduce COVID-19 morbidity and improve treatment response for pulmonary tuberculosis.

Perhaps the obsession with vitamin D stems from the allure of a simple solution for complex problems. Consider orthopaedics: From degenerative joint disease in young people to socioeconomic disparities, so many challenges we face treating MSK problems have multivariate causations. For surgeons, even when the diagnosis is easy, the solution can be complicated. Compare piecing together a complex intra-articular fracture with recommending 600 IU of over-the-counter vitamin D. Even if the surgeon achieves anatomic reduction, we want to believe that the miracle vitamin will ameliorate the chondrocyte damage.

Determining vitamin deficiency
Decades of research have demonstrated that vitamin D deficiency extends far beyond the elderly or institutionalized. However, optimal levels remain controversial. For example, the Institute of Medicine and the National Academy of Medicine recommend 20 ng/mL as an adequate serum concentration. The National Osteoporosis Foundation and Endocrine Society recommend 30 ng/mL as the optimal concentration. A trial with more than 15,000 available baseline serum vitamin D levels found an average of about 30 ng/mL in American adults, and 13 percent had <20 ng ml. the implications of deficiency, the optimal serum benchmarks, and the appropriate indications for level testing remain opaque, but the financial impact of the vitamin d testing frenzy is clear. in 2015, cms spent $337 million on vitamin d testing, and despite a choosing wisely recommendation against population-based laboratory screening for vitamin d, an estimated 10 million vitamin d levels are checked annually in the united states.></20>

More dilemma than delightful?
Despite the myriad diseases associated with deficiency, the literature also suggests that the magic of vitamin D might be a chimera. Positive impacts make for popular headlines, and the null results end up on back pages. Most of the highly touted findings emerged in observational studies that did not stand up to the rigor of randomized, controlled trials. The level 1 VITAL trial found that supplementation was not effective in preventing cardiovascular or cancer events. Even more surprising, in generally healthy patients, supplementation with vitamin D did not even reduce the incidence of fractures over the placebo arm. The level 1 ViDA trial in New Zealand found similar failure of vitamin D supplementation. Digging deeper into the relationship with chronic inflammation, early observational nutritional studies have been disputed by more robust randomized trials. The inverse association between vitamin D and elevated C-reactive protein appears to hold true only in deficiency states, and causation remains unproven. With obesity, causation remains unproven. Rather, deficiency may be related to dilution and sequestration in the greater body volumes of fat, blood, muscle, and liver. Patients with high BMI may even have diminished response to vitamin D supplementation.

Certainly, data support multiple clear benefits for repleting deficient vitamin D levels. Given the ease and low cost, supplementation for insufficiency also makes sense. Ordering serum levels on low-risk adults seems a poor use of resources. Channeling Cole Porter again:

So, control your desire to curse
While I crucify the verse:
It’s delightful, it’s delicious, it’s delectable, it’s delirious
It’s dilemma, it’s de-limit, it’s deluxe, it’s de-lovely …

It’s D-vitamin.

For now, I will keep the vitamin D in my cupboard next to the ibuprofen, but if I have a serum level over 30 ng/mL, I may have hit D-limit of this purported panacea of the 21st century. Perhaps I should still reserve shelf space for the elixir I plan to bring home when I find the Fountain of Youth.

Alexandra E. Page, MD, FAAOS, is a foot and ankle specialist in private practice in San Diego and the deputy editor of AAOS Now.

References

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  15. Centers for Medicare & Medicaid Services: Medicare Coverage Database: Local Coverage Determination—Vitamin D Assay Testing. Available at: https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39391&ver=6. Accessed Feb. 15, 2024.
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  18. Porter C: “It’s De-Lovely.” 1934.