Vitamin D deficiency in adults

Recognizing and managing vitamin D deficiency in adults: Key insights.
Maha Khalifa, BS Pharm, PharmD, BCPS, MSc

Introduction

Vitamin D deficiency is characterized by hypocalcemia and/or hypophosphatemia and rickets in children and osteomalacia in adults. When interpreting a vitamin D level, you are really asking, “Is this vitamin D level adequate to meet my patient’s needs?” The problem is that some patients may have a greater or lesser need for vitamin D than others. We can’t actually know what an individual patient’s need is. Patients with Vitamin D (25-hydroxyvitamin D) level < 20 ng/mL (50 nmol/L) are at risk of vitamin D deficiency (i.e., rickets or osteomalacia). we favor maintaining the serum 25(OH)D concentration between 20 and 40 ng/mL (50 to 100 nmol/L). Vitamin D deficiency may affect levels of calcium, phosphorus, and even bone metabolism. Risk Factors for vitamin D deficiency are listed below, "see table 1".

Most adults with vitamin D deficiency are asymptomatic, but those with severe vitamin D deficiency may have musculoskeletal symptoms such as pain or weakness and if untreated can cause complications such as osteomalacia, and secondary hyperparathyroidism. Common causes of vitamin D deficiency may be due to insufficient dietary intake, malabsorption, decreased synthesis in the skin (such as, people with dark skin pigmentation, aging, or lack of sunlight exposure), kidney impairments, medications, and impaired hepatic metabolism.

NPS-adv

Table (1). Risk Factors for Vitamin D Deficiency
RISK FACTORS
  • Age older than 65 years.
  • Breastfed exclusively without vitamin D supplementation.
  • Dark skin.
  • Insufficient sunlight exposure (using sunscreen with sun protection factor > 15).
  • Medication use that alters vitamin D metabolism (e.g., anticonvulsants, glucocorticoids).
  • Obesity (body mass index greater than 30 kg per m2).
  • Sedentary lifestyle.
  • Renal or liver disease.
  • Smoking.
This information from, Am Fam Physician. 2009 Oct 15;80(8):841-846.

Diagnosis

Investigation

Be sure to measure 25-hydroxyvitamin D, NOT 1,25-dihydroxyvitamin D, in most patients. 1,25-dihydroxyvitamin D levels do not correlate with vitamin D stores; they are regulated by parathyroid hormone. In vitamin D deficiency, 1,25-hydroxyvitamin D levels actually go up. It is appropriate to check 1,25-dihydroxyvitamin D levels in patients with hypercalcemia (as part of the diagnostic workup), and perhaps end-stage renal disease (because vitamin D activation is impaired). The test should be recommended only for patients at risk for vitamin D deficiency, such as patients with chronic kidney disease, hypocalcemia, hyperparathyroidism, osteoporosis, obesity or a malabsorption syndrome.

History and physical are important to specify the underlying causes such as liver disease and conditions such as celiac disease that in turn causes gastrointestinal absorption defects. Blood tests for parathyroid hormone, calcium, phosphorus, and alkaline phosphatase levels may be considered. patients with bone pain Imaging studies may be performed such as radiographic imaging, computed tomography (CT), and magnetic resonance imaging (MRI) to help in identifying fractures and bone scans (bone scintigraphy) may help detect abnormal metabolic bone activity.

Management

Pharmacotherapy

For patients with symptomatic disease or patients who will start treatment with potent antiresorptive agents (bisphosphonates, etc), they require rapid correction of vitamin D level, treatment will include fixed loading doses followed by regular maintenance therapy. A loading dose of 300,000 units of vitamin D in total can be given either as separate weekly or daily doses over 6 to 10 weeks.

  • Loading regimen options
    • 50,000 units (1,250 mcg) of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) once weekly for 6 weeks (300,000 units) while vitamin D3 is preferred than vitamin D2 in achieving the desired serum level of 25-hydroxyvitamin D > 30 ng/mL (75 nmol/L).
    • 40,000 units (1000 mcg) orally once weekly for 7 weeks (280,000 units).
    • 6000 units (150 mcg) orally, once per day for 8 weeks (336,000 units).
    • 1000 units (25 mcg) orally, 4 times per day for 10 weeks (280,000 units).
    • 800-unit (20 mcg) orally, 5 times per day given for 10 weeks (280,000 units).

Tweet Screenshot
Figure (1)
Vitamin D supplementation algorithm.

Maintenance therapy of vitamin D in doses equivalent to 800 to 2000 units (20 mcg-50 mcg) daily, up to a maximum of 4000 units (100mcg) daily is then given. For other patients who are not in need to rapid correction of vitamin D levels or patients who will have vitamin D supplements with an oral antiresorptive agent (bisphosphonates, etc), treatment will include maintenance dose without initiation of loading doses.

Practice

  • Patients with chronic renal failure, nephrotic syndrome, or severe malabsorption syndromes start with calcitriol, 1, 25-dihydroxycholecalciferol analogue (One Alpha, Bone Care, etc) orally or IV.
  • Patients with severe liver disease or impaired hepatic metabolism due to drugs start with calcifediol, 25-hydroxyvitamin D3 (Davalindi 1000 IU).
  • Patients with malabsorption consider intramuscular vitamin D.
  • Consider a dose of 1000 mg of calcium daily for men and premenopausal women with vitamin D deficiency and a dose of 1200 mg of calcium daily for postmenopausal females with vitamin D deficiency.
  • Consider Calcium plus vitamin D not vitamin D alone in older adults preventing bone fracture and falls and reducing mortality.

Nutrition care

Nutritional counselling, dietary sources of vitamin D include supplements and food, food sources of vitamin D such as salmon, sardines, tuna, cod liver oil, and egg yolk or dietary supplements are in the form of vitamin D2 or vitamin D3, "see table 2".

Table (2). Food Sources of Vitamin D
FOOD STANDARD PORTION CALORIES VITAMIN D (IU)
Protein Foods
Rainbow trout, freshwater 3 ounces 142 645
Salmon (various) 3 ounces ~115-175 383-570
Light tuna, canned 3 ounces 168 231
Herring 3 ounces 172 182
Sardines, canned 3 ounces 177 164
Tilapia 3 ounces 108 127
Flounder 3 ounces 73 118
Dairy and Fortified Soy Alternatives
Soy beverage (soy milk), unsweetened 1 cup 80 119
Milk, low fat (1 %) 1 cup 102 117
Yogurt, plain, nonfat 8 ounces 137 116
Yogurt, plain, low fat 8 ounces 154 116
Milk, fat free (skim) 1 cup 83 115
Kefir, plain, low fat 1 cup 104 100
Cheese, American, low fat or fat free, fortified 1 1/2 ounces 104 85
Vegetables
Mushrooms, raw (various) 1 cup ~15-20 114-1110
Fruit
Orange juice, 100%, fortified 1 cup 117 100
Other Sources
Almond beverage (almond milk), unsweetened 1 cup 36 107
Rice beverage (rice milk), unsweetened 1 cup 113 101
This information from: Food Sources of Vitamin D | Dietary Guidelines for Americans. [online] Available at: https://www.dietaryguidelines.gov/resources/2020-2025-dietary-guidelines-online-materials/food-sources-select-nutrients/food-sources.

Monitoring treatment

Check serum level of 25-hydroxyvitamin D 10-12 weeks after starting therapy, and reassessing treatment if level is < 30 ng/mL (75 nmol/L), despite that Royal Osteoporosis Society guidelines not suggest routine monitoring of plasma 25-hydroxyvitamin D but may be helpful in patients with symptomatic vitamin D deficiency, malabsorption, or suspected poor drug compliance.

Check adjusted plasma calcium 1 month after completing the loading regimen or after starting lower dose vitamin D supplementation: hypercalcemia may be a sign of a coexisting primary hyperparathyroidism. Check for possible toxicities with excessive serum vitamin D (> 100 ng/mL [250 nmol/L]) such as hypercalciuria, hypercalcemia, hyperphosphatemia, and possible increased risk of falls.

NPS-adv

References

  1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
  2. National Institutes of Health (2017). Vitamin D. [online] Nih.gov. Available at: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional.
  3. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T113821, Vitamin D Deficiency in Adults; [updated 2018 Dec 04, cited March 11, 2022]. Available from https://www.dynamed.com/topics/dmp~AN~T113821. Registration and login required.
  4. Narvaez J, Maldonado G, Guerrero R, Messina OD, Rios C. Vitamin D Megadose: Definition, Efficacy in Bone Metabolism, Risk of Falls and Fractures. Open Access Rheumatol. 2020 Jun 11;12:105-115.