• US Preventive Services Task Force (2021). For community-dwelling, nonpregnant, asymptomatic adults, the USPSTF concluded that evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency (I statement). No studies directly evaluating the benefits or harms of screening were identified. This recommendation does not apply to people who are hospitalized or institutionalized, who are pregnant, who have conditions for which treatment is indicated (including osteomalacia, malabsorption, or chronic kidney disease), or who take medications that increase deficiency risk.^[1]
• Endocrine Society (2024; reaffirmed in 2025). In healthy adults who are not at increased risk, the guideline suggests against routine 25-OHD screening (weak recommendation, very-low-certainty evidence).^[2][3]

Neither recommendation supports population-wide 25-OHD testing of healthy, asymptomatic adults. Higher-risk or symptomatic individuals require a different clinical approach, in which targeted testing is used for case-finding rather than population screening.

Because formal population screening for osteomalacia is not established, clinicians should consider targeted biochemical case-finding in individuals with relevant risk factors or minimal nonspecific symptoms. Examples include dark skin pigmentation, limited effective sun exposure or concealing clothing, institutionalization, pregnancy or lactation, malabsorptive disorders, chronic kidney or liver disease, and relevant medications.^[4]

A reasonable initial biochemical case-finding panel includes:

• Serum calcium
• Serum phosphate
• Serum alkaline phosphatase (ALP)
• Serum 25-hydroxyvitamin D (25-OHD)
• Parathyroid hormone (PTH)
• Assessment of dietary calcium intake

Abnormalities should trigger a diagnostic evaluation rather than be treated as diagnostic of osteomalacia. Detailed biochemical interpretation and confirmatory investigations belong in the Laboratory Findings and Other Diagnostic Studies microchapters.

Uday and Högler proposed non-invasive criteria for identifying nutritional osteomalacia without requiring bone biopsy. The proposed approach emphasizes:

• High ALP
• High PTH
• Low dietary calcium intake (<300 mg/day) and/or low 25-OHD (<30 nmol/L)
• Support from compatible clinical findings or Looser zones when present

These criteria are proposed rather than prospectively validated and should therefore be used as a case-finding framework rather than as definitive diagnostic criteria.^[4]

A non-invasive case-finding algorithm was also evaluated in British Asian outpatients. In this study, 160 patients were evaluated and 45 underwent biopsy. A clinical score was highly sensitive (8 of 9 cases) but not specific, while PTH was the single best biochemical discriminator. A discriminant function combining PTH and ALP correctly classified 96% of cases, compared with 85% using calcium, phosphate, and ALP. The authors recommended measuring PTH and ALP in patients with an abnormal clinical score; high PTH and high ALP in the absence of hypercalcemia made histologic osteomalacia extremely likely in that dataset.^[5]

An older biopsy-anchored study defined biopsy-proven osteomalacia as osteoid volume >10% and osteoid width >15 µm. All patients had at least two of low calcium, low phosphate, elevated ALP, or a suggestive radiograph. ALP was elevated in 94%, whereas PTH was elevated in only 41%. The authors concluded that PTH offered no apparent benefit as a screening test and that calcium, phosphate, ALP, and radiography could serve as initial investigations in clinically suggestive patients.^[6]

Thus, PTH’s screening value is directly disputed between two biopsy-anchored datasets. Nisbet et al. found PTH to be the single best biochemical discriminator, with PTH + ALP correctly classifying 96% of cases, whereas Bingham–Fitzpatrick found PTH elevated in only 41% and concluded that it offered no apparent benefit as a screening test. Uday–Högler nonetheless include high PTH as a core proposed criterion.^[5][6][4]

A low 25-OHD concentration alone does not establish osteomalacia. Biochemical osteomalacia in nutritional vitamin D deficiency is associated with severe and persistent vitamin D deficiency, generally at concentrations substantially below thresholds commonly used to define vitamin D insufficiency. In a cohort of 42,171 25-OHD measurements, the prevalence of biochemical osteomalacia was only 0.02% overall and 0.23% among measurements with 25-OHD <25 nmol/L; all pre-supplementation cases had 25-OHD ≤18 nmol/L.^[7]

These findings reinforce that vitamin D insufficiency should not be equated with osteomalacia and provide context for targeted rather than population-wide case-finding.

Conversely, a normal 25-OHD does not exclude osteomalacia. Phosphopenic osteomalacia and disorders of vitamin D activation may occur despite normal 25-OHD; therefore, testing should be guided by the clinical and biochemical pattern rather than by 25-OHD alone.^[6]

1. Do not perform population-wide 25-OHD screening in healthy, asymptomatic adults.
2. Consider targeted case-finding in individuals with substantial risk factors or minimal nonspecific symptoms using calcium, phosphate, ALP, 25-OHD, PTH, and assessment of dietary calcium intake.
3. Use proposed non-invasive criteria as case-finding tools, not definitive diagnostic criteria. The Uday–Högler criteria remain unvalidated prospectively, while the Nisbet algorithm provides supportive evidence from a biopsy-anchored cohort.
4. Interpret PTH in context. Evidence regarding its value as a case-finding test is conflicting between biopsy-anchored studies.
5. Do not equate vitamin D insufficiency with osteomalacia. A low 25-OHD concentration requires clinical and biochemical interpretation.
6. Do not use a normal 25-OHD concentration to exclude osteomalacia when the clinical or biochemical pattern suggests a phosphopenic or vitamin D–activation disorder.
7. Proceed to diagnostic evaluation when abnormalities or clinical findings raise suspicion. Confirmatory biochemical and specialized investigations are addressed in the Laboratory Findings and Other Diagnostic Studies microchapters.