Hypophosphatasia Clinical Trials 2026 — Find Recruiting Studies

About Hypophosphatasia

Hypophosphatasia is a metabolic bone disease caused by loss-of-function variants in ALPL, encoding tissue-nonspecific alkaline phosphatase (TNSALP), resulting in defective bone and tooth mineralisation due to accumulation of natural substrates including inorganic pyrophosphate and pyridoxal-5'-phosphate. Clinical severity spans from lethal perinatal disease with profound unmineralised bone to isolated premature loss of deciduous teeth in childhood or stress fractures in adulthood. Enzyme replacement therapy with asfotase alfa is approved for paediatric-onset disease, creating an important distinction for trial eligibility.

Common Clinical Features

Premature loss of deciduous teeth with intact roots (before age 5) Rachitic bone disease with bowing and fractures in childhood Low or absent serum alkaline phosphatase activity Elevated plasma pyridoxal-5'-phosphate (a TNSALP substrate) Respiratory failure from thoracic hypomineralisation in neonates Stress fractures and poor fracture healing in adults Seizures responsive to pyridoxine (vitamin B6) in perinatal forms

Clinical Trial Eligibility Tips

What to know before applying to Hypophosphatasia trials.

Alkaline phosphatase activity (serum ALP) and plasma PLP levels are diagnostic biomarkers required at screening — ensure these are drawn fasting and without recent vitamin B6 supplementation.

Patients receiving asfotase alfa enzyme replacement therapy may be excluded from some trials or may qualify for different arms; disclose current and prior treatment history in detail.

Radiographs documenting skeletal manifestations (rachitic changes, pseudofractures, or tongue-of-radiolucency at metaphyses) are commonly required as part of baseline imaging.