A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients

Ng, Elisabeth; Ashkar, Claudia; Seeman, Ego; Schneider, Hans G.; Nguyen, Hanh H.; Ebeling, Peter R.; Sztal‐Mazer, Shoshana

doi:10.1007/s00198-022-06597-3

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…A recent observational study demonstrated that 0.3% (5/1839) of the patients attending an osteoporotic clinic were diagnosed with HPP based on screening the level of ALP activity. [29] There were some limitations in this study. First, this is a case report, and further studies including healthy people, patients with chronic kidney disease, or a larger number of patients with HPP are required to address whether uPPi/Cre could be an alternative marker to plasma PPi.…”

Section: Discussionmentioning

confidence: 90%

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The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult‐Onset Hypophosphatasia

Hidaka,

Murata,

Tachikawa

et al. 2023

JBMR Plus

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Hypophosphatasia (HPP) is an inherited disease caused by variants of the ALPL gene encoding tissue‐nonspecific alkaline phosphatase. Adult‐onset HPP (adult HPP), known as a mild form of HPP, develops symptoms involving osteomalacia after the age of 18 years. Asfotase alfa (AA) is a modulated recombinant human alkaline phosphatase (ALP) that has been established as a first‐line therapy for severe forms of HPP, such as perinatal and infantile forms. We described a 64‐year‐old female who presented with pseudofractures in bilateral femur diaphyses and impaired mobility. Low serum ALP activity and a high concentration of urine phosphoethanolamine indicated the diagnosis of HPP, which was confirmed by the identification of a homozygous variant in the ALPL gene (c.319G > A; p.Val107Ile). An in vitro transfection experiment to measure the ALP activity of this novel variant protein was performed, resulting in 40% of the residual enzymatic activity compared with the wild type. AA was initiated to facilitate the union of pseudofracture and to improve mobility. After 6 months, radiographic images revealed the disappearance of fracture lines, and improvement of ambulatory ability was confirmed by the 6‐minute walk test (525 to 606 m). The EQ‐5D‐5L index was also improved (0.757 to 0.895). Within a follow‐up period, the levels of urine pyrophosphate corrected by urine creatinine (uPPi/Cre) declined in parallel with the level of plasma PPi (plasma PPi: 6.34 to 1.04 μM, uPPi/Cre: 226.8 to 75.4 nmol/mg). The beneficial effect of AA on pseudofracture healing in adult HPP was presented, although the application of AA should be restricted to patients exhibiting relatively severe manifestations. In addition, a novel pathogenic variant of the ALPL gene was identified with the supportive result of functional analysis. Furthermore, when monitoring patients with HPP treated with AA, uPPi/Cre might be a convenient substitute for plasma PPi, which requires immediate filtration after blood sampling. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 90%

“…A recent observational study demonstrated that 0.3% (5/1839) of the patients attending an osteoporotic clinic were diagnosed with HPP based on screening the level of ALP activity. [ 29 ]…”

Section: Discussionmentioning

confidence: 99%

The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult‐Onset Hypophosphatasia

Hidaka,

Murata,

Tachikawa

et al. 2023

JBMR Plus

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“…On the other hand, the prevalence of HPP is high. In osteoporosis clinics, the prevalence of HPP was as high as 0.3–0.43% [ 41 , 42 ]. Misdiagnosis is common in adult HPP [ 33 , 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Adults

Ren

Wang

et al. 2023

Genes

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Hypophosphatasia (HPP) is an inherited disease caused by ALPL mutation, resulting in decreased alkaline phosphatase (ALP) activity and damage to bone and tooth mineralization. The clinical symptoms of adult HPP are variable, making diagnosis challenging. This study aims to clarify the clinical and genetic characteristics of HPP in Chinese adults. There were 19 patients, including 1 with childhood-onset and 18 with adult-onset HPP. The median age was 62 (32–74) years and 16 female patients were involved. Common symptoms included musculoskeletal symptoms (12/19), dental problems (8/19), fractures (7/19), and fatigue (6/19). Nine patients (47.4%) were misdiagnosed with osteoporosis and six received anti-resorptive treatment. The average serum ALP level was 29.1 (14–53) U/L and 94.7% (18/19) of patients had ALP levels below 40 U/L. Genetic analysis found 14 ALPL mutations, including three novel mutations—c.511C>G (p.His171Ala), c.782C>A (p.Pro261Gln), and 1399A>G (p.Met467Val). The symptoms of two patients with compound heterozygous mutations were more severe than those with heterozygous mutations. Our study summarized the clinical characteristics of adult HPP patients in the Chinese population, expanded the spectrum of pathogenic mutations, and deepened clinicians’ understanding of this neglected disease.

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Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study

Kimura,

Sunouchi,

Watanabe

et al. 2024

Osteoporos Int

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Summary Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. Purpose The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. Methods Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. Results Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase , biomineralization associated ( ALPL ), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. Conclusion If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-024-07168-4.

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A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients

Cited by 5 publications

References 33 publications

The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult‐Onset Hypophosphatasia

The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult‐Onset Hypophosphatasia

Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Adults

Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study

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