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.

Adult hypophosphatasia (HPP) is caused by genetic variations in the ALPL gene causing a loss-of-function, leading to disruptions in normal skeletal mineralization processes. However, the impact of adult HPP extends beyond the skeletal system, as the ubiquitous expression and involvement of the affected enzyme in the body's metabolic processes result in a broad spectrum of symptoms. Consequently, individuals with HPP mostly experience a diminished quality of life (QoL). The severity and presentation of the disease are highly heterogeneous. Despite this variability, the underlying reasons and contributing factors remain poorly understood. This study aims to get a better understanding of HPP patients QoL and identify parameters that correlate with their QoL. To address this, our study retrospectively analyzed 146 adult patients diagnosed with HPP. Health-related quality of life was assessed using the Short Form Health Survey version 1.0 (SF-36 v1), and pain levels were assessed using the brief pain inventory. Our findings indicate that HPP compromises not only physical health but also significantly impacts mental well-being, with a Physical Component Summary of 39.9 and a Mental Component Summary of 39.3. Moreover, we observed that patients' QoL was inversely associated with factors such as obesity, lower concentrations of alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BAP). Additionally, indicators of physical status demonstrated a strong correlation with QoL. These results underscore the need for a systematic approach to monitoring both somatic parameters and mental health in adult HPP patients to help evaluate disease progression, treatment effects, and overall patient condition. Clinicians can utilize objective criteria, namely physical status indicators, ALP and BAP concentrations, and BW as additional tools in assessing patients' conditions, as these factors are linked to QoL in HPP. This may help clinicians estimate patients disease status and may help to assess and monitor the impact of therapy on QoL.

Hypophosphatasia is a rare metabolic bone disorder that is often misdiagnosed. We present the case of a middle-aged woman initially misdiagnosed with rickets and later as osteogenesis imperfecta and treated with zoledronate, after which she developed atypical femoral fractures. After switching to teriparatide therapy, her bone mineral density improved significantly. This case underscores that persistently low alkaline phosphatase with fragility or atypical fractures should prompt evaluation for hypophosphatasia and that antiresorptives (eg, bisphosphonates) may precipitate atypical fractures in this condition and should be avoided. Disease-specific therapy is enzyme replacement with asfotase alfa; anabolic therapy may improve bone mineral density in selected adults when asfotase alfa is unavailable.

The aim of this study was to investigate the influence of overweight (BMI ≥ 25 (kg/m²)) on the oral health status in patients with adult hypophosphatasia (HPP). Throughout a retrospective assessment both oral health status and bone metabolism including dual x-ray absorptiometry (DXA) for bone mineral density (BMD) measures were analyzed. The oral health status was assessed by the decayed/missing/filled teeth index (DMFT), clinical attachment level (CAL), probing pocket depth (PPD), and the periodontal screening index (PSI). The study population was divided into two groups based on the overweight classification by BMI (Overweight = BMI ≥ 25 kg/m²; n = 17) vs. non-overweight ( BMI < 25 kg/m²; n = 31). 48 HPP patients were included in this study. Overweight HPP patients showed a significantly reduced oral health status regarding filled teeth, DMFT, PSI, PPD and periodontitis severity index compared to non-overweight HPP patients. Furthermore, overweight HPP patients revealed significantly higher DXA findings regarding BMD, T- and Z-scores. In the present study overweight (BMI ≥ 25 (kg/m²)) is associated with a poorer oral health status and higher BMD in adult HPP. Since overweight is associated with a poorer oral health status in the general population and promotes the development of periodontal disease, the findings of the present study indicate that overweight also affects oral health in adult HPP.

Hypophosphatasia (HPP) is a rare inherited bone disorder with systemic symptoms, which vary depending on the time of onset and other factors. It may be fatal or cause severe clinical symptoms in infants and children. By comparison, adult HPP generally has a more favorable prognosis, and it is usually associated with chronic pain, recurrent fractures, and impaired quality of life. However, the diagnosis of adult HPP is often delayed or it may remain undiagnosed. Additionally, treatment options for adult HPP are not well established. We report a male patient in his 50s who experienced recurrent fractures in his 40s and 50s, together with chronic pain. He was diagnosed with HPP due to low serum alkaline phosphatase levels and a heterozygous missense variant of the ALPL gene (c.529G>A). He therefore started enzyme replacement therapy with asfotase alfa. After 12 months of treatment with asfotase alfa, his motor function showed marked improvement and he experienced fewer falls and no new fragility fractures, although his chronic pain remained.