Low alkaline phosphatase in adults: implications for the diagnosis of hypophosphatasia during evaluation for osteoporosis
Authors' conclusion
Very low ALP strongly indicates HPP, yet the clinical spectrum extends beyond strict biochemical thresholds. ALP level-independent of genetic status-predicts fracture risk, suggesting residual enzyme activity is clinically relevant.
Study context
- Population
- Adults referred for thyroid, endocrine, osteoporosis or rheumatological conditions in whom low alkaline phosphatase (ALP) was identified
- Participants
- 33 adults
- Exposure
- ALPL variant-positive vs ALPL variant-negative adults with low ALP
- ALPL-positiven = 20
- Outcome
- Predictors of genetically confirmed hypophosphatasia (HPP)
Methodological detailssingle-centre
- Single-centre
Main finding
As reported in the abstract
- All individuals with ALP ≤ 25 IU/L had a detectable disease-causing variant
- ALP was often higher in variant-positive patients
- PLP levels differed significantly between groups
- Bone-specific ALP, standard biochemical markers and DXA T-scores did not differ between groups
Observational data: associations, not effects.
Further findings
- Overall fracture prevalence similar between groups
- Each 7.8 IU/L decrease in ALP significantly increased fracture probability, independent of genotype
- Peripheral fractures predominated
Safety
Contraindicated treatment
- Patients who received bisphosphonates before diagnosis
- 1
Original publication
Low alkaline phosphatase in adults: implications for the diagnosis of hypophosphatasia during evaluation for osteoporosis. Osteoporos Int. Published 5 August 2026. doi:10.
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