What are the recommendations for screening serum 25‑hydroxyvitamin D levels in adults, particularly those over 65 years, with osteoporosis or low‑impact fractures, malabsorption syndromes, chronic kidney disease, obesity, limited sun exposure, darker skin pigmentation, chronic glucocorticoid or anticonvulsant therapy, or who are pregnant or lactating?

Vitamin D Screening Recommendations

Primary Recommendation: Targeted Testing Only

Routine screening of asymptomatic adults for vitamin D deficiency is not recommended; testing should be reserved exclusively for individuals with specific risk factors or conditions that substantially increase the likelihood of deficiency. 1, 2

The U.S. Preventive Services Task Force assigns an "I" (insufficient evidence) grade to population-wide screening, concluding that current evidence cannot determine whether screening asymptomatic adults improves health outcomes such as fractures, falls, cardiovascular disease, or mortality. 1

---

High-Risk Populations Who Warrant Testing

Skeletal & Fall Risk

• Adults ≥65 years with osteoporosis, osteopenia, or history of low-impact fractures 3, 4
• Individuals with recurrent falls or high fracture risk 3, 4
• Secondary hyperparathyroidism of unclear etiology 3, 4

Malabsorption Syndromes

• Post-bariatric surgery (especially Roux-en-Y gastric bypass or biliopancreatic diversion) 3
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 3
• Celiac disease, pancreatic insufficiency, or short-bowel syndrome 3

Chronic Kidney Disease

• CKD stages 3–5 (GFR <60 mL/min/1.73 m²) or dialysis patients 3, 2
• Annual measurement recommended, with monitoring every 3 months during repletion 2
• Vitamin D insufficiency affects 80–90% of CKD patients 2

Lifestyle & Physiologic Factors

• Dark skin pigmentation (African American, Hispanic, Asian populations living at higher latitudes) 1, 2
  • African Americans have 2–9 times higher prevalence of low 25(OH)D but half the fracture risk of white individuals, suggesting bioavailable vitamin D may differ from total measured levels 1, 2
• Limited sun exposure: homebound, institutionalized, extensive clothing coverage, or residence at high latitude 1, 2
• Obesity: vitamin D is sequestered in adipose tissue, though a portion remains bioavailable 1, 2

Medication-Related Risk

• Chronic glucocorticoid therapy 3, 4
• Chronic anticonvulsant therapy 3, 4

Pregnancy & Lactation

• Pregnant or lactating women, particularly those with additional risk factors 3, 4

---

Alternative to Testing: Empiric Supplementation

For elderly (≥65 years), institutionalized, dark-skinned individuals with limited sun exposure, or those with extensive clothing coverage, empiric supplementation with 800 IU vitamin D daily is reasonable without prior testing. 3, 2

• This dose meets the needs of 97.5% of adults over 70 years and avoids the cost and variability of testing 2
• Testing in these populations may be deferred unless clinical suspicion for severe deficiency exists 3, 2

---

Critical Limitations of Vitamin D Assays

Analytical Variability

• Inter-assay variability ranges from 10–25%, with classification of deficiency differing by 4–32% depending on the assay used 2, 5
• No internationally recognized reference standard exists, making sensitivity and specificity unknown 2, 5
• Laboratories should use assays that measure both 25(OH)D₂ and 25(OH)D₃ and participate in external quality-control programs 3, 2

Biological Confounders

• 25(OH)D acts as a negative acute-phase reactant: levels decrease during inflammation (CRP >40 mg/L), leading to misinterpretation in acutely ill patients 3, 2
• Ethnic differences: total 25(OH)D may underestimate adequacy in African Americans, as bioavailable vitamin D (accounting for binding-protein differences) may be sufficient despite lower total levels 1, 2

---

Monitoring After Initiating Supplementation

• Re-measure serum 25(OH)D 3 months after starting or adjusting therapy to allow levels to plateau 3, 2
• Measuring earlier than 3 months does not reflect steady-state levels and may lead to inappropriate dose adjustments 3, 2
• For intermittent dosing regimens (weekly or monthly), measure immediately before the next scheduled dose 3
• Once target levels (≥30 ng/mL) are achieved and stable, annual monitoring is sufficient 3

---

Common Pitfalls

• Do not order vitamin D testing in asymptomatic, average-risk adults: poor assay standardization combined with lack of proven screening benefit makes this practice wasteful and potentially harmful through overdiagnosis 1, 2
• Avoid interpreting isolated low 25(OH)D values in patients with acute illness or elevated inflammatory markers, as vitamin D acts as a negative acute-phase reactant 3, 2
• Do not assume a single "normal" reference range applies universally across ethnic groups: bioavailable vitamin D may differ substantially from total measured levels, particularly in African Americans 1, 2
• Do not rely on sun exposure for vitamin D repletion due to increased skin cancer risk from UVB radiation 3

---

Safety Thresholds

• Deficiency: <20 ng/mL (requires treatment) 3, 4
• Insufficiency: 20–30 ng/mL (supplementation should be considered) 3, 4
• Optimal range: 30–44 ng/mL for musculoskeletal, cardiovascular, and cancer-preventive benefits 3, 6, 7
• Upper safety limit: 100 ng/mL; levels above this increase toxicity risk 3, 4
• Toxicity manifestations: hypercalcemia, hyperphosphatemia, suppressed PTH, hypercalciuria 1, 3