ArticleBone2015
Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl-/- mice by administration of soluble (non-targeted) chimeric alkaline phosphatase.
Article in Bone, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- TNAP and PHOSPHO1 Function Synergistically to Afford Critical Control Over the Mineralization of the Postnatal Murine Skeleton.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- TNAP and PHOSPHO1 function synergistically to afford critical control over the mineralisation of the postnatal murine skeleton.bioRxiv : the preprint server for biology · 2026Article
- A Case of Hypophosphatasia Started Enzyme Replacement Therapy Since Babyhood Stage.Children (Basel, Switzerland) · 2025Article
- Effects of Infantile Hypophosphatasia on Human Dental Tissue.Calcified tissue international · 2023Article
- The RGD region of bone sialoprotein affects metabolic activity in mice.Frontiers in dental medicine · 2023Article
- Anabolic actions of parathyroid hormone in a hypophosphatasia mouse model.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Article
- Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts.International journal of molecular sciences · 2022Article
- Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?Frontiers in dental medicine · 2022Article
- Prenatal enzyme replacement therapy forRegenerative therapy · 2021Article
- Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-DJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- SixAnnals of translational medicine · 2021Article
- GSK3β rephosphorylation rescues ALPL deficiency-induced impairment of odontoblastic differentiation of DPSCs.Stem cell research & therapy · 2021Article
- Tissue-Nonspecific Alkaline Phosphatase-A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease.Biomolecules · 2020Review
- Transcriptional Regulation of Dental Epithelial Cell Fate.International journal of molecular sciences · 2020Review
- Identification of Biomarkers for Osteosarcoma Based on Integration Strategy.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Inhibitory Effect ofOxidative medicine and cellular longevity · 2020Article
- Alkaline Phosphatase Replacement Therapy for Hypophosphatasia in Development and Practice.Advances in experimental medicine and biology · 2019Review
- Hypophosphatasia: From Diagnosis to Treatment.Current rheumatology reports · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Hypophosphatasia (HPP) results from ALPL gene mutations, which lead to a deficiency of tissue-nonspecific alkaline phosphatase (TNAP), and accumulation of inorganic pyrophosphate, a potent inhibitor of mineralization that is also a natural substrate of TNAP, in the extracellular space. HPP causes mineralization disorders including soft bones (rickets or osteomalacia) and defects in teeth and periodontal tissues. Enzyme replacement therapy using mineral-targeting recombinant TNAP has proven effective in preventing skeletal and dental defects in TNAP knockout (Alpl(-/-)) mice, a model for life-threatening HPP. Here, we show that the administration of a soluble, intestinal-like chimeric alkaline phosphatase (ChimAP) improves the manifestations of HPP in Alpl(-/-) mice. Mice received daily subcutaneous injections of ChimAP at doses of 1, 8 or 16 mg/kg, from birth for up to 53 days. Lifespan and body weight of Alpl(-/-) mice were normalized, and vitamin B6-associated seizures were absent with 16 mg/kg/day of ChimAP. Radiographs, μCT and histological analyses documented improved mineralization in cortical and trabecular bone and secondary ossification centers in long bones of ChimAP16-treated mice. There was no evidence of craniosynostosis in the ChimAP16-treated mice and we did not detect ectopic calcification by radiography and histology in the aortas, stomachs, kidneys or lungs in any of the treatment groups. Molar tooth development and function improved with the highest ChimAP dose, including enamel, dentin, and tooth morphology. Cementum remained deficient and alveolar bone mineralization was reduced compared to controls, though ChimAP-treated Alpl(-/-) mice featured periodontal attachment and retained teeth. This study provides the first evidence for the pharmacological efficacy of ChimAP for use in the treatment of skeletal and dental manifestations of HPP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.