Jansen's Disease: Bone Abnormalities Beyond Chondrodysplasia
Authors' conclusion
The H223R-PTH1R mutation in patients with JMC leads to bone structural irregularities, hypomineralization, abnormal osteocyte morphology, and altered expression of osteocyte-derived proteins. These findings underscore the multifaceted impact of the mutant PTH1R on bone physiology and focus attention on the osteocyte as a cellular target for therapeutic intervention. Whether normalizing gene expression in osteocytes is possible and can improve bone health in patients with JMC remains to be seen. Assessment of osteocyte morphology and function may provide novel diagnostic endpoints for future clinical trials with JMC therapeutics.
Study context
- Population
- Pediatric male patients with Jansen metaphyseal chondrodysplasia (JMC) and healthy male controls of similar age
- Participants
- 2 vs 9
- Comparison
- JMC patients with H223R-PTH1R mutation vs healthy control males
- JMCn = 2
- Controlsn = 9reference
- Outcome
- Bone histomorphometry, immunohistochemistry and histology of iliac crest biopsies
Methodological detailscase series with healthy controls, iliac crest biopsy
- Case series with healthy controls
- Iliac crest biopsy
Main finding
As reported in the abstract
- Both JMC patients: irregular bone architecture, increased osteoid, prolonged osteoid maturation
- Trabecular volume normal
- Increased PTH1R expression in osteoblasts and fibroblastic cells on bone surface
- Cortical bone: areas of intense osteoclast activity and scattered marrow fibrosis
- Osteocytes with osteoid buildup in lacunae; canaliculi shorter and less abundant
- DMP1 immunohistochemistry highlighted abnormal canalicular network
- Osteocyte FGF23 staining enhanced; sclerostin diminished
Original publication
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