ReviewCalcified tissue international2025
Diagnosis and Treatment of Hypophosphatasia.
Review in Calcified tissue international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed.
- A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Trial
- Evolving Therapeutic Paradigms in Pediatric Hypophosphatasia: From Survival-Driven Care to Integrated Precision Management.International journal of molecular sciences · 2026Review
- [Metabolic bone disorders: what the internist must not overlook].Innere Medizin (Heidelberg, Germany) · 2026Review
- Biochemical phenotype of hypophosphatasia in asymptomatic individuals carrying ALPL variants.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Interpreting Low Alkaline Phosphatase in Fibromyalgia: The Importance of Comprehensive Clinical and Biochemical Assessment.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Article
- Infantile hypophosphatasia caused by compound heterozygous variants in theAmerican journal of translational research · 2026Article
- The Challenge of Hypophosphatasia Diagnosis in Patients with Fibromyalgia.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Article
- Decoding the secretory blueprint of bone healing: from gradients to regeneration.Frontiers in cell and developmental biology · 2026Review
- Review
- Clinical diagnosis and challenges in management of Osteogenesis Imperfecta in a resource-limited setting - A case report and review of literature.International journal of surgery case reports · 2025Article
- The Global Hypophosphatasia Registry: lessons learned from a decade of real-world data.Orphanet journal of rare diseases · 2025Review
- AI-assisted phenotyping in a zebrafish hypophosphatasia model enables early and precise detection of skeletal alterations.Scientific reports · 2025Article
- Vitamin B6 challenge as a tool for detecting ALPL mutations and diagnosing hypophosphatasia.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Article
- Evaluation of Low Alkaline Phosphatase Levels in Clinical Practice: Implications for Diagnosing Hypophosphatasia.Calcified tissue international · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of tissue-nonspecific alkaline phosphatase (TNAP) caused by variants in the ALPL gene. Disease manifestations encompass skeletal hypomineralization with rickets and lung hypoplasia, vitamin B6-dependent seizures, craniosynostosis, and premature loss of deciduous teeth. The clinical presentation can comprise failure to thrive with muscular hypotonia, delayed motor development, and gait disturbances later in childhood. In adults, pseudofractures are a characteristic indicator of severely compromised enzyme activity, but non-canonical symptoms like generalized musculoskeletal pain, weakness, and fatigue, frequently accompanied by neuropsychiatric and gastrointestinal issues are increasingly recognized as key findings in patients with HPP. The diagnosis is based on clinical manifestations in combination with persistently low alkaline phosphatase (ALP) activity, elevated levels of ALP substrates, specifically inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), and genetic confirmation of a causative ALPL variant. Considering the wide range of manifestations, treatment must be multimodal and tailored to individual needs. The multidisciplinary team for comprehensive management of HPP patients should include expertise to ensure disease state metabolic and musculoskeletal treatment, dental care, neurological and neurosurgical surveillance, pain management, physical therapy, and psychological care. Asfotase alfa as first-in-class enzyme replacement therapy (ERT) for HPP has been shown to improve survival, rickets, and functional outcomes in severely affected children, but further research is needed to refine how enzyme replacement can also address emerging manifestations of the disease. Prospectively, further elucidating the pathophysiology behind the diverse clinical manifestations of HPP is instrumental for improving diagnostic concepts, establishing novel means for substituting enzyme activity, and developing integrative, multimodal care.
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