Hypophosphatasia and Type 1 Diabetes: A Pilot Study and Review of Literature

Hypophosphatasia (HPP) and type 1 diabetes (T1D) are both associated with low bone turnover and increased fracture risk. In this review, our objectives were to (a) discuss results of our pilot study aimed to evaluate prevalence and clinical and radiological characteristics of HPP in adults with T1D and (b) to review literature on the use of electronic medical records (EMR) for HPP case findings.

In our pilot study, 18 individuals had persistent low alkaline phosphatase levels (ALP) [18/1723, 1.05%]. Among 10 participants who completed the study with potential HPP and T1D, three had a pathogenic ALPL mutation (0.16% prevalence), and six had elevated serum vitamin B6. No significant differences were found in DXA-based bone density, QCT-based bone density, or Finite element-estimated bone strength between the potential HPP group, T1D adults, and controls. We did not find any study that evaluated persistent low ALP levels or potential HPP in patients with diabetes (either type 1 or type 2 diabetes). The literature reported higher prevalence of low ALP levels when electronic medical records were searched (~ 1–3%). However, prevalence of suspected HPP based on persistent low ALP levels and/or clinical signs and symptoms was around 0.5% or lower depending on sample size, methods and geographical locations.

Our study suggests that EMR-based screening for HPP is feasible and may identify previously undiagnosed cases of HPP. Prevalence of potential HPP in T1D is around 1% and genetically confirmed HPP is 0.16% which is similar to reported prevalence of HPP in selected population without diabetes. Skeletal imaging and clinical presentations are not sufficient for identifying potential HPP in individuals with T1D. Given the increased fracture risk and low bone turnover typically seen in T1D, we propose that an EMR-based screening strategy could be a more effective approach for diagnosing HPP in T1D population.