ArticleThe New England journal of medicine2016
Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease.
Article in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 147 citations in OpenAlex.
- A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth.EBioMedicine · 2024Trial
- Sfrp4 Is Required for Proper Dental Formation and Stem Cell Regulation.Journal of dental research · 2026Article
- The pathogenesis and intersecting mechanisms of monogenic bone mass disorders.Nature reviews. Endocrinology · 2026Review
- Case Report: Cortical bone loss, impaired mineralization, and reduced adiposity contributing to chronic bone pain in SFRP4-related skeletal disease with an ALPL variant.Frontiers in endocrinology · 2026Article
- Wnt16: a new potential therapeutic target for osteoporotic non-vertebral fracture treatment.Frontiers in aging · 2026Review
- Fibro-NPC: a pathogenic subtype identified at single-cell resolution with secreted SFRP4 as a biomarker in intervertebral disc degeneration.Journal of translational medicine · 2025Article
- Genotype-Phenotype Correlation Insights in a Rare Case Presenting with Multiple Osteodysplastic Syndromes.Genes · 2025Article
- Aging Alters mRNA Processing in the Mouse Ovary.Cells · 2025Article
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Paradoxical combination of osteosclerosis and osteopenia in an adult woman with biallelicJBMR plus · 2025Article
- Identification and function of periosteal skeletal stem cells in skeletal development, homeostasis, and disease.Journal of orthopaedic translation · 2025Review
- Gene expression patterns of the developing human face at single cell resolution reveal cell type contributions to normal facial variation and disease risk.bioRxiv : the preprint server for biology · 2025Article
- Roles of osteoclasts in pathological conditions.Pathology international · 2025Review
- Electrodiagnostic Findings in a Case of Pyle's Disease: A Case-Report.Iranian journal of child neurology · 2025Article
- Naked cuticle homolog 2 controls the differentiation of osteoblasts and osteoclasts and ameliorates bone loss in ovariectomized mice.Genes & diseases · 2025Article
- Osteopetrosis-like disorders induced by osteoblast-specific retinoic acid signaling inhibition in mice.Bone research · 2024Article
- Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone.Endocrine reviews · 2024Review
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Aseptic loosening around total joint replacement in humans is regulated by miR-1246 and miR-6089 via the Wnt signalling pathway.Journal of orthopaedic surgery and research · 2024Article
- Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
24 authors.
Funding
Abstract
backgroundCortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments.
methodsWe evaluated four patients with Pyle's disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture.
resultsIn all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle's disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect.
conclusionsOur study showed that Pyle's disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.).
Indexed as
Identifiers
What OpenQuestion holds
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.