Academic Journal
Combined treatment with a C-type natriuretic peptide analog and bisphosphonate enhances bone growth in growing mice with osteogenesis imperfecta: a pilot study.
| Τίτλος: | Combined treatment with a C-type natriuretic peptide analog and bisphosphonate enhances bone growth in growing mice with osteogenesis imperfecta: a pilot study. |
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| Συγγραφείς: | Mulcrone JE; Hospital for Special Surgery, HSS Research Institute, New York, NY 10021, United States., Seide K; Hospital for Special Surgery, HSS Research Institute, New York, NY 10021, United States., Chacko J; Hospital for Special Surgery, HSS Research Institute, New York, NY 10021, United States., Carter EM; Hospital for Special Surgery, HSS Research Institute, New York, NY 10021, United States., Pleshko N; Temple University, Department of Bioengineering, Philadelphia, PA 19122, United States., Derocher CE; Hospital for Special Surgery, HSS Research Institute, New York, NY 10021, United States., Raggio CL; Hospital for Special Surgery, HSS Research Institute, New York, NY 10021, United States. |
| Πηγή: | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2026 Jul 01; Vol. 41 (7), pp. 762-771. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8610640 Publication Model: Print Cited Medium: Internet ISSN: 1523-4681 (Electronic) Linking ISSN: 08840431 NLM ISO Abbreviation: J Bone Miner Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: January 2024- : [Oxford] : Oxford University Press Original Publication: New York : Mary Ann Liebert, Inc., c1986- |
| Ιατρικοί όροι (MeSH): | Osteogenesis Imperfecta*/drug therapy , Osteogenesis Imperfecta*/diagnostic imaging , Osteogenesis Imperfecta*/pathology , Osteogenesis Imperfecta*/physiopathology , Natriuretic Peptide, C-Type*/pharmacology , Natriuretic Peptide, C-Type*/analogs & derivatives , Natriuretic Peptide, C-Type*/therapeutic use , Bone Development*/drug effects , Diphosphonates*/pharmacology , Diphosphonates*/therapeutic use, Bone Density/drug effects ; Femur/pathology ; Femur/drug effects ; Femur/diagnostic imaging ; Animals ; Pilot Projects ; Mice ; Female ; Male |
| Περίληψη: | Osteogenesis imperfecta (OI) is a heterogeneous type 1 collagenopathy characterized by recurrent fractures, decreased bone mass, and short stature. Bisphosphonates reduce fracture incidence in children with OI, but do not improve growth velocity. C-type natriuretic peptide (CNP) is produced in the growth plate (also in the brain and heart), and it positively regulates linear bone growth; people with OI have been shown to have reduced serum levels of CNP. This pilot study evaluated whether a CNP analog combined with alendronate (ALN) improves growth and BMD in oim/oim (OIM) mice, a model of moderate-to-severe Type III OI. Two-wk-old OIM and WT mice received weekly ALN and 1 of 3 CNP regimens: 10 μg/kg 3 d/wk (low), 20 μg/kg 3 d/wk (medium), or 20 μg/kg 5 d/wk (high). Controls received saline. Faxitron images were taken at 2, 8, and 14 wk (sacrifice) to assess fracture incidence and measure femoral length and vertebral height. MicroCT was used to assess bone microstructural parameters of the femur ex vivo. The high-dose group had no fractures post-sacrifice, while 1 fracture each was observed in the low and medium dose groups. Femoral length increased in all treated groups, with the high dose-group showing the greatest increase (8.2% and significant) in OIM mice. Vertebral height increased in all treated groups; low and high dose groups had greater and comparable increases than the medium group in OIM mice. All treated groups showed increased trabecular BMD. Cortical tissue mineral density, BMD, and thickness were also elevated in all treated groups compared to the controls. In conclusion, CNP analog adjuvant treatment enhanced linear growth and bone quality without compromising fracture reduction, providing benefits not seen with bisphosphonates alone. These results will inform optimal dosing for future studies. A full murine study is planned to further evaluate the therapeutic potential for translation to humans. (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| Contributed Indexing: | Keywords: antiresorptives; bone QCT/microCT; fracture prevention; growth plate; injury/fracture healing; osteogenesis imperfecta; preclinical studies; therapeutics Local Abstract: [plain-language-summary] Osteogenesis imperfecta (OI) is a genetic disorder that causes fragile bones and stunted growth. While current treatments such as bisphosphonates help reduce fractures, they do not improve height. This pilot study tested whether adding a new treatment based on a natural growth regulator (C-type natriuretic peptide [CNP]) could help. Young mice with OI were treated with both CNP and bisphosphonates, which led to fewer fractures, longer bones, and stronger bone structure compared to bisphosphonates alone. These promising results suggest that a CNP could enhance bone growth and quality in OI. |
| Substance Nomenclature: | 127869-51-6 (Natriuretic Peptide, C-Type) 0 (Diphosphonates) |
| Entry Date(s): | Date Created: 20251211 Date Completed: 20260701 Latest Revision: 20260701 |
| Update Code: | 20260702 |
| DOI: | 10.1093/jbmr/zjaf190 |
| PMID: | 41378917 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1523-4681 |
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| DOI: | 10.1093/jbmr/zjaf190 |