Lab Interpretation: Low vitamin D (25-OH vitamin D) in adults

ALGORITHM — 

(algorithm 1)

INITIAL EVALUATION — 

Serum 25-hydroxyvitamin D (25(OH)D) concentrations are measured in high-risk adults to estimate vitamin D sufficiency. There are several causes of vitamin D deficiency (table 1). The etiology is often apparent from the history and physical examination. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Candidates for 25(OH)D measurements' and "Causes of vitamin D deficiency and resistance".)

25-hydroxyvitamin D <12 ng/mL (30 nmol/L) — Patients with 25(OH)D <12 ng/mL (30 nmol/L) are at risk for developing osteomalacia and, therefore, require laboratory evaluation. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Evaluation' and "Clinical manifestations, diagnosis, and treatment of osteomalacia in adults".)

Obtain:

●Calcium, phosphorus, parathyroid hormone (PTH)

●Alkaline phosphatase

●Electrolytes, blood urea nitrogen (BUN), creatinine

●Tissue transglutaminase (tTG) antibodies (to assess for celiac disease)

For patients with bone pain in the pelvis and lower extremities, obtain radiographs of affected sites to assess for stress fractures or Looser zones (pseudofractures), findings that are suspicious for osteomalacia.

Although bone mineral density (BMD) of the spine, hip, and forearm (as measured by dual-energy x-ray absorptiometry [DXA]) may be markedly reduced in patients with osteomalacia related to vitamin D deficiency, BMD is not required for the diagnosis of osteomalacia, and BMD findings are unable to differentiate osteomalacia and osteoporosis. Patients with low 25(OH)D levels require vitamin D supplementation regardless of the findings on BMD.

Many patients have serum 25(OH)D levels assessed as part of an evaluation for osteoporosis (diagnosed on BMD or due to a fragility fracture). In such patients with severely low 25(OH)D levels (and particularly if the serum PTH is high), the need for osteoporosis therapy should be reevaluated after vitamin D replenishment. In severely vitamin D-deficient patients, there can be marked increases in BMD after treatment of osteomalacia with calcium and vitamin D supplementation, such that treatment for "osteoporosis" is not necessary. Similarly, treatment of celiac disease with a gluten-free diet can result in significant improvement in BMD. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement'.)

25-hydroxyvitamin D 12 to 20 ng/mL (30 to 50 nmol/L) — The majority of healthy adults with vitamin D deficiency in this range do not require any additional evaluation; however, some experts measure similar tests as when 25(OH)D is <12 ng/mL (30 nmol/L), particularly if the level is 12 to 15 ng/mL (30 to 37.5 nmol/L), or there is concern for a secondary cause of vitamin D deficiency (eg, malabsorption, celiac disease).

Patients with vitamin D in this range should receive supplementation. Vitamin D should be replenished cautiously in patients with underlying primary hyperparathyroidism, granulomatous disease, or metastatic bone disease since worsening hypercalcemia and hypercalciuria have been reported in these settings.

Measure serum 25(OH)D levels approximately three to four months after initiating supplementation with vitamin D. For patients who are compliant with vitamin D supplementation but have no or minimal increase in the serum 25(OH)D levels, we measure tTG antibodies (if not previously measured) to assess for celiac disease. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement' and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Monitoring' and "Diagnosis of celiac disease in adults".)

25-hydroxyvitamin D >20 ng/mL (50 nmol/L) — No further evaluation is needed for vitamin D level >20 ng/mL. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement'.)

REFERENCE RANGE — 

The optimal 25(OH)D for skeletal health is controversial. The lower limit of normal is approximately 20 ng/mL (50 nmol/L). Levels vary with the assay method used. Commercial assays measure total 25(OH)D, but some laboratories report 25(OH)D2 and 25(OH)D3 values separately. It is the total 25(OH)D concentration that is clinically important.

CITATIONS — 

The supporting references for this content are accessible in the linked topics.