Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study

Summary: Hypophosphatasia (HPP) is a rare disease affecting bone mineralization. Adults with HPP have an increased occurrence of low-energy fractures, which cannot be explained by reduced bone mass assessed by dual energy X-ray absorptiometry. The bone phenotype in adults with HPP requires further studies investigating bone strength and bone structural parameters. Introduction: Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism, characterized by broad-ranging clinical manifestations and severity. However, studies investigating the clinical spectrum in adults with HPP compared to a control group are scarce. The aim of this study was to evaluate biochemical and clinical characteristics as well as bone health in a Danish cohort of adults with HPP. Methods: We conducted a cross-sectional study assessing biochemical parameters, fracture prevalence, bone mineral density (BMD), bone turnover markers, physical performance and pain characteristics in 40 adults with HPP and 40 sex-, age-, BMI- and menopausal status-matched healthy controls. Results: Patients with HPP had a significantly higher prevalence of non-vertebral, low-energy fractures (p = < 0.001). BMD at the lumbar spine, total hip, femoral neck, forearm and whole body did not differ between the groups. Low levels of the bone-specific alkaline phosphatase correlated significantly with higher BMD at the lumbar spine and femoral neck in both groups. The bone formation marker N-terminal propeptide of type 1 procollagen was significantly lower in patients with HPP than healthy controls (p = 0.006). Adults with HPP had significantly reduced walking capability (p = < 0.001) and lower body strength (p = < 0.001). Chronic pain was significantly more prevalent in adults with HPP than the control group (p = 0.029). Conclusions: The increased occurrence of low-energy fractures in adults with HPP is not explained by low BMD. Adults with HPP have reduced physical performance when compared with healthy controls.