Bone Marrow Cell Transplants Model Phosphate Dysregulation in Osteoglophonic Dysplasia

Bone marrow stromal cells (BMSCs) carrying an osteoglophonic dysplasia–associated fibroblast growth factor receptor 1 (FGFR1) variant produced elevated fibroblast growth factor 23 (FGF23) and reduced phosphate after transplantation into mice, according to preliminary findings presented at the American Society for Bone & Mineral Research (ASBMR) 2026 Annual Meeting. The researchers developed the transplant model to study phosphate dysregulation and evaluate infigratinib after the biochemical and skeletal changes become established.

Osteoglophonic dysplasia is a rare skeletal disorder caused by activating FGFR1 variants. The researchers previously developed a knock-in mouse model carrying the FGFR1 p.N330I variant. Those mice showed small size, craniosynostosis, craniofacial abnormalities, impaired growth plate organization, elevated FGF23, and FGF23-mediated hypophosphatemia. In the earlier model, 15 days of treatment with the FGFR inhibitor infigratinib partially rescued the skeletal phenotype. Infertility limited the availability of mutant mice for further study.

For the current transplant study, the researchers isolated BMSCs from the long bones of wild-type and FGFR1 p.N330I mice, expanded the cells in culture, and loaded them into gelatin foam scaffolds. They placed the scaffolds in bilateral subcutaneous dorsal pockets of immunocompromised NSG mice.

Preliminary results showed increased plasma FGF23 and reduced phosphate beginning approximately 40 days after transplantation, with further progression over the following days (P < .01). Histology of transplants containing mutant BMSCs showed an absence of cortex. Bone volume fraction was approximately 42% lower (P < .05), and whole-body bone mineral density in mice with mutant ossicles was approximately 18% lower (P < .05). The abstract did not report the number of donor or recipient mice.

The researchers plan to start infigratinib at 2 mg/kg three times weekly between 30 and 50 days after transplantation. They are monitoring circulating FGF23, phosphate, and ossicle formation over time. Planned endpoint analyses include micro-CT, histology, and FGF23 RNAscope testing of the transplants and femurs. The abstract reports no results from this planned treatment phase.

The abstract describes human osteoglophonic dysplasia as the condition the mouse models are intended to represent; it reports no human participants or human treatment findings. The researchers propose that the transplant model could help establish whether cells carrying the FGFR1 variant drive FGF23 dysregulation and provide a platform for testing FGFR-targeted therapies. Those mechanistic and treatment questions remain under investigation.

Reference

Kaur R, Ascone G, Galisteo R, et al. A BMSC transplantation model to study FGFR1-FGF23-phosphate dysregulation and evaluate infigratinib in osteoglophonic dysplasia. Abstract presented at: American Society for Bone & Mineral Research 2026 Annual Meeting; October 9-12, 2026; Boston, MA. Accessed October 7, 2026. https://eppro01.ativ.me/web/index.php?page=IntHtml&project=ASBMR26&id=p7118