Screening and patient exploration for adult hypophosphatasia in orthopedics

Hypophosphatasia is an inherited metabolic bone disorder characterized by cartilage and bone abnormalities. Adult hypophosphatasia presents with a wide range of symptoms, including refractory fractures, recurrent fractures, stress fractures, and reduced bone mineral density, along with extraskeletal manifestations such as myalgia, muscle weakness, and fatigue. Some patients with these symptoms may have undiagnosed hypophosphatasia. While hypophosphatasia is treatable with enzyme replacement therapy, early diagnosis is often difficult owing to its diverse clinical presentations. This study aimed to create a screening method for identifying suspected hypophosphatasia cases.

We retrospectively reviewed all adult patients of orthopedics (2392 cases; 859 men and 1533 women, mean age 71.0 ± 18.7 years) who underwent serum alkaline phosphatase testing at our hospital between April 1, 2022, and March 31, 2023. Patients with at least one alkaline phosphatase level below the lower limit of normal (38 U/L) were included. Patients who consistently showed low alkaline phosphatase levels in all tests were classified as suspected hypophosphatasia cases. We investigated the fracture history, musculoskeletal symptoms, and alkaline phosphatase levels of these patients to identify potential hypophosphatasia cases.

Eight patients (0.33 %) were suspected of having hypophosphatasia. Of the two patients who were followed up, one was diagnosed with hypophosphatasia through genetic testing.

Our screening method can extract suspected hypophosphatasia cases. Our study is the first to propose and apply a targeted screening approach for adult hypophosphatasia in an orthopaedic cohort-an at-risk population that has not been previously examined in this context. Orthopaedic surgeons should be aware of the possibility of hypophosphatasia in patients presenting with fractures or pain and consider alkaline phosphatase levels cautiously.