BoneKEy Reports | BoneKEy Watch
Steroids prevent rib fragility in a transgenic mouse model
DOI:10.1038/bonekey.2013.59
Duan et al. generated an adult mouse model of rib fragility by deleting the gene encoding β-catenin in osteoblasts expressing Col1a2. The knockout was tamoxifen inducible and gene deletion was achieved by giving 8-week old mice intra-peritoneal injections of 10 mg/ml tamoxifen for 11 days.
Within days of the final injection, mice developed labored breathing and died. They had developed multiple and spontaneous rib fractures and showed extensive bone resorption within the ribs and deformities of the chest wall. Increased serum levels of RANKL were apparent and enhanced bone resorption occurred at the femur and in the vertebrae.
Mice treated with the bisphosphonate (BP) pamidronate (5 mg/kg) concurrently with tamoxifen lived longer, but only one in five were still alive at 65 days after the last tamoxifen/BP dose. Treatment with the glucocorticoid dexamethasone was more successful. Mice given 1 mg/kg dexamethasone three times a week during tamoxifen treatment and for the rest of the study showed higher bone volume in their ribs (46% greater than tamoxifen-only mice) and extensive remodeling of bone at 65 days; 75% of the mice survived to that time point. The underlying mechanism may have involved decreased expression of RANKL by inflammatory cells, as occurs in inflammatory arthritis.
Editor’s comment: This study provides evidence that steroids (known for inducing bone loss with prolonged use) may be useful for treating rapid bone loss, for example in advanced cancers, where pathological fractures cause morbidity and decrease quality of life.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.