Related Experiment Video
Updated: May 19, 2026
Exploring Independent Effects of Follicle-Stimulating Hormone In Vivo in a Mouse Model
Published on: August 11, 2023
High- and low-dose OPG-Fc cause osteopetrosis-like changes in infant mice
Renee Bargman1, Ram Posham, Adele Boskey
1Department of Pediatrics, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, New York, USA.
Background:
Receptor activator of nuclear factor-κB ligand (RANKL) inhibitors are being considered for use in children with osteogenesis imperfecta (OI). We sought to assess efficacy of two doses of a RANKL inhibitor, osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc), in a growing animal model of OI, the col1α2-deficient mouse (oim/oim) and its wild-type controls (+/+).
Methods:
Treated mice showed runting and radiographic evidence of osteopetrosis with either high- (20 mg/kg twice weekly) or low-dose (1 mg/kg/week) OPG-Fc. Because of this adverse event, OPG-Fc treatment was halted, and the mice were killed or monitored for recovery with monthly radiographs and assessment of serum osteoclast activity (tartrate-resistant acid phosphatase 5b, TRACP-5b) until 25 wk of age.
Results:
Twelve weeks of OPG-Fc treatment resulted in radiographic and histologic osteopetrosis with no evidence of bone modeling and negative tartrate-resistant acid phosphatase staining, root dentin abnormalities, and TRACP-5b activity suppression. Signs of recovery appeared 4-8 wk post-treatment.
Conclusion:
Both high- and low-dose OPG-Fc treatment resulted in osteopetrotic changes in infant mice, an outcome that was not seen in studies with the RANKL inhibitor RANK-immunoglobulin Fc segment complex (RANK-Fc) or in studies with older animals. Further investigations of RANKL inhibitors are necessary before their consideration for use in children.
Insights
Receptor activator of nuclear factor-κB ligand (RANKL) inhibitors like OPG-Fc caused osteopetrosis in young OI mice. Further research is needed before using RANKL inhibitors in children with osteogenesis imperfecta.
Area of Science:
- Pediatric Endocrinology
- Skeletal Biology
- Pharmacology
Background:
- Receptor activator of nuclear factor-κB ligand (RANKL) inhibitors are being investigated for treating osteogenesis imperfecta (OI) in children.
- Osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc) is a specific RANKL inhibitor considered for this application.
Purpose of the Study:
- To evaluate the efficacy and safety of two OPG-Fc doses in a pediatric OI animal model.
- To assess the impact of OPG-Fc on bone development and osteoclast activity in growing oim/oim mice.
Main Methods:
- Infant col1α2-deficient (oim/oim) mice and wild-type controls were treated with high-dose (20 mg/kg twice weekly) or low-dose (1 mg/kg/week) OPG-Fc.
- Treatment duration was 12 weeks, followed by monitoring for recovery with radiographs and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) assessment.
Main Results:
- Both OPG-Fc doses induced runting and radiographic/histologic osteopetrosis in infant oim/oim mice.
- Osteopetrosis was characterized by suppressed TRACP-5b activity, lack of bone modeling, and absence of root dentin abnormalities.
- Recovery signs, including normalization of TRACP-5b activity, appeared 4-8 weeks after OPG-Fc cessation.
Conclusions:
- High- and low-dose OPG-Fc treatments led to adverse osteopetrotic changes in young OI mice, unlike studies with RANK-Fc or older animals.
- These findings suggest caution regarding RANKL inhibitor use in pediatric OI patients.
- Further investigation is required to determine the safety and efficacy of RANKL inhibitors for children with osteogenesis imperfecta.
