Bone remodeling as an expression of altered phenotype: studies of fracture healing in untreated and cured osteopetrotic rats.

The healing of tibial fractures was studied in 3 groups of young littermate rats; untreated osteopetrotic (ia/ia), normal littermates (ia/+) and osteopetrotic (ia/ia) cured of the disease 3 days earlier by transplanted normal spleen cells. The fracture site was completely remodeled in 4 weeks in normal rats, 6 weeks in transplanted (cured) osteopetrotic rats and 9 weeks in untreated osteopetrotic rats. The delayed healing in untreated osteopetrotic rats resulted from reduced resorption present in this mutation. Increased resorption brought about by transplantation of normal spleen cells accelerated healing in the transplanted osteopetrotic rats. Fracture repair took longer in the latter group than in normal littermates presumably because tibial fracture occurred before the 2 week interval required for skeletal transformation from osteopetrotic to normal phenotype following transplantation of normal spleen cells. These data show that alteration of the phenotype of osteopetrotic rats is reflected in fracture healing.