- Design
- Cross-sectional study with nested randomised placebo-controlled trial
- Population
- 423 Norwegian adults with low 25-hydroxyvitamin D (mean 34 nmol/L); 382 randomised
- Primary outcome
- Prevalence of biochemical patterns compatible with osteomalacia
- Effect
- 0% with full pattern; 8.3% with most permissive pattern
A cross-sectional study with a nested randomised trial in Calcified Tissue International (23 September 2026) measured PTH, calcium and alkaline phosphatase in 423 adults from the population-based Tromsø study with low vitamin D (mean 25-hydroxyvitamin D 34 nmol/L). 382 were then randomised to vitamin D (100,000 IU loading, then 20,000 IU weekly for four months) or placebo.
None had the full pattern of raised PTH, raised alkaline phosphatase and low calcium. Using the most permissive pattern, 8.3% qualified. Vitamin D lowered PTH and alkaline phosphatase and raised calcium against placebo.
Without bone biopsy, these patterns cannot confirm or exclude osteomalacia, and the authors say so. But for the physician, the finding is useful: a low 25-hydroxyvitamin D in an otherwise well adult is not, by itself, a diagnosis of bone disease.
- Do not diagnose osteomalacia from a low vitamin D level alone
- Check calcium, phosphate, alkaline phosphatase and PTH in a patient with bone pain, proximal weakness or a raised ALP
- Suspect osteomalacia when a low vitamin D comes with raised ALP and low calcium or phosphate
- Replacing vitamin D does lower PTH and ALP — recheck them after treatment where they were abnormal
Why it matters
It questions whether thresholds defining vitamin D 'deficiency' identify people who actually have bone disease.
Don't overread it
Without bone histology, these biochemical patterns cannot establish the true prevalence of osteomalacia.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for internal medicine, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free