Practice Perfect 695
The Ever-Important Fourth Vitamin - D

When it comes to taking care of patients with foot and ankle disorders, one of the most frustrating aspects is dealing with unknowns. The biggest unknown or uncertainty in my mind is deficiency of the fourth vitamin discovered. You guessed it; when vitamins were first discovered around 1919, they named them in order. “Fat-soluble factor A,” later vitamin A was the first, with B, and C to follow.  Vitamin D, then, was the fourth vitamin – and first one for which a Nobel prize was awarded.1 This vitamin was first characterized in response to rickets, but today we often hear about it as the cause of almost every problem in the body from diabetes to nonunions after surgery to heart disease, and vitamin D supplements seem to be the new panacea for whatever ails us. Let’s take a quick, high-yield tour of the vitamin D world and see what we know and don’t know to refresh our memories.

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Vitamin D Physiology

There are five subtypes of vitamin D, but the ones we are most concerned with are D2 (ergocalciferol – synthetically made by irradiating ergosterol, the fungal cell wall sterol constituent, with ultraviolet light), and D3 (cholecalciferol – made from 7-dehydrocholestol in the skin when exposed to UVB radiation and also absorbed by the intestines from certain foods).

Vitamin D3 (cholecalciferol) is converted in the liver to 25-hydroxycholecalciferol (AKA calcidiol). This is the chemical we measure in the serum when checking vitamin D levels (see “Testing” below). Calcidiol is then processed in the kidneys to 1,25 dihydroxycholecalciferol (calcitriol) caused by increased parathyroid hormone (resulting from low serum calcium), which promotes intestinal calcium absorption, promotes bone resorption (due to increased osteoclast activity), and decreases parathyroid hormone (PTH) levels (in a negative feedback loop). All of these have the effect of increasing plasma calcium. Vitamin D also has the somewhat more mysterious effect of simultaneously increasing osteoblast activity. Yes, vitamin D does both increase and decrease calcium in the blood. Vitamin D is thought to have both a mineralization effect (discussed here) called the classical action and a hormonal action (beyond the scope of this discussion). For the interested, I’ve included a diagram showing the mineralization effect of vitamin D and the important function of parathyroid hormone.

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Testing

Vitamin D levels are checked using serum 25-hydroxyvitamin D (25(OH)D or calcidiol) concentrations. Optimal serum levels are 20-40 ng/mL. Some controversy exists in these numbers with some experts stating 30 ng/mL is the minimum acceptable level. Given this difference of opinion, and 30 ng/mL being right in the middle, my suggestion is to use 30 ng/mL as your minimum normal cutoff.

My suggestion is to use 30 ng/mL of Calcidiol as your minimum normal cutoff.

Prevalence

Without citing a ton of research articles, we know hypovitaminosis D is highly common. After reading through several studies looking at the prevalence of vitamin D deficiency and the effect of vitamin D deficiency on orthopedic podiatric surgery, I came away with no new information. The studies universally find a high prevalence of vitamin D deficiency in patients undergoing various orthopedic and podiatric surgeries and that functional outcomes are worse in those patients with deficiency. The problem with all of these studies is that vitamin D deficiency may be a marker of poor health leading to worse outcomes rather than being the actual cause of those poor outcomes. Remember this: very high prevalence (> 60% in some studies) and the outcomes are generally worse in those patients with deficiency compared with healthy people. Surprise!

The studies universally find a high prevalence of vitamin D deficiency in patients undergoing various orthopedic and podiatric surgeries and that functional outcomes are worse in those patients with deficiency.

3 States of Vitamin D Levels

Sufficiency: 25(OH)D > 20 ng/mL
Insufficiency: 25(OH)D 12 - 20 ng/mL
Deficiency: 25(OH)D < 12 ng/mL

Recommendations to Prevent Deficiency2

The Institute of Medicine recommends the following:

  • Adults and children (everyone < 70 years-old) should receive 600 IU of vitamin D3 daily
  • Anyone > 70 years should receive 800 IU of vitamin D3

Recommendations to Treat Deficiency

Vitamin D deficient adults are recommended to receive 50,000 IU of vitamin D2 or D3 once per week for 8 weeks or 6,000 IU per day with a goal to achieve a serum level of 30 ng/mL. Maintenance therapy should then follow with a vitamin D2 or D3 dose of 1500-2000 IU/day.2

Sources of Vitamin D

UV radiation (AKA the sun) – Vitamin D produced in the skin will last approximately twice as long as the ingested version3. UV radiation exposure that causes a slight pink of the skin 24 hours after exposure is equivalent to taking 10,000-25,000 IU orally.4

Foods – Cod liver oil, fresh wild caught salmon, shitake mushrooms all contain Vitamin D at levels at or above the recommended daily allowance.

Supplements – Centrum®Silver® contains 1,000 IU, while other supplements contain anywhere from 200 IU to 800 IU. Have patients look for 600-800 IU to prevent deficiency, but remember that supplements are not FDA regulated, so doses may vary from pill to pill.

Vitamin D and Foot & Ankle Care

There are a lot of topics we could focus on, but let’s stick with the elephant in the operating room: the possibility of nonunions after surgery. Unfortunately, there is a paucity of powerful studies with strong methodology to guide our decisions.

In 2017, Moore and colleagues retrospectively examined two matched cohorts of patients who underwent elective foot and ankle surgery, 29 patients with nonunions and 29 patients with successful healing. When they looked at the patients with endocrine disease (vitamin D deficiency, thyroid disease, diabetes, and parathyroid disease) 76% of them had nonunions versus 26% in the non-endocrine disease patients. Patients with vitamin D deficiency or insufficiency were 8.1 times more likely to experience a nonunion.5

In Moore et al’s study, patients with vitamin D deficiency or insufficiency were 8.1 times more likely to experience a nonunion.5

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I applaud Moore’s group for taking on this project and giving us something to consider. Unfortunately, there are literally no other studies to consider. My search terms “Vitamin D nonunion foot ankle” only came up with Moore’s study.

Based on this tiny bit of data that may link nonunions in the foot and ankle with vitamin D deficiency, the very high prevalence of hypovitaminosis D, and what we know about the metabolism of this vitamin, it makes sense to be cautious and test vitamin D levels preop and supplement with relatively high doses before elective surgeries and during the recovery phases after emergent surgery. Measure at the very least 25(OH) vitamin D and calcium levels and supplement accordingly. The more sophisticated might consider ordering ionized calcium (the only type of serum calcium that is metabolically active) instead of total calcium that is commonly reported. May the fourth - vitamin be with you!

It makes sense to be cautious and test vitamin D levels preop and supplement with relatively high doses before elective surgeries and during the recovery phases after emergent surgery.
Best wishes.

Jarrod Shapiro, DPM
PRESENT Practice Perfect Editor
jarrod@podiatry.com
References
  1. Wolf G. The Discovery of Vitamin D: The Contribution of Adolf Windaus. J Nutr. 2004 Jun;134(6):1299-1302.
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  2. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-1930.
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  3. Haddad JG, Matsuoka LY, Hollis BW, Hu YZ, Wortsman J. Human Plasma Transport of Vitamin D after Its Endogenous Synthesis.J Clin Invest. 1993 Jun;91(6):2552-2555.
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  4. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S-6S.
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  5. Moore KR, Howell MA, Saltrick KR, Catanzariti AR. Risk Factors Associated With Nonunion After Elective Foot and Ankle Reconstruction: A Case-Control Study. J Foot Ankle Surg. 2017 May - Jun;56(3):457-462.
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