Effects of increased bone formation on fracture healing in mice.
BACKGROUND
Fracture healing is a complex and sequential process. One important step in fracture healing is callus remodeling. As we could previously show, an increase of osteoclast bone resorption as a result of estrogen deficiency impairs the fracture healing process. Therefore, the aim of our study was to analyze whether an increased bone formation, as the counterpart of bone resorption in callus remodeling, would accelerate the fracture healing process.


METHODS
Standardized femoral fractures were produced in 10-week-old control, leptin-deficient (ob/ob), and leptin receptor-deficient (db/db) mice using a guillotine-like fracture device. Accordingly, the fractures were intramedullary stabilized. The ob/ob and db/db mice are known to have a twofold increase in bone formation in comparison with normal wildtype mice. At different stages of fracture healing, contact X-ray, histologic, and biomechanical analyses were performed.


RESULTS
We observed that a twofold increase in bone formation leads to an accelerated periosteal callus formation followed by callus remodeling. As compared with the control group, chondrocytes area was increased, and the subsequent mineralization appeared earlier. In the late stage of fracture healing, the ob/ob and db/db mice showed a thinner but increased mineralized cortex. Biomechanical testing confirmed the beneficial effects of an increased bone formation on restoration of biomechanical competence.


CONCLUSIONS
These results indicate that bone formation is of major importance in all stages of fracture healing. A twofold increase in bone formation is able to significantly accelerate the fracture healing process of long bones at least in mice. Therefore, an increase in bone formation would be a possible pharmaceutical target to enhance fracture healing.
Beil
Frank Timo
FT
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Barvencik
Florian
F
Gebauer
Matthias
M
Beil
Britta
B
Pogoda
Pia
P
Rueger
Johannes Maria
JM
Ignatius
Anita
A
Schinke
Thorsten
T
Amling
Michael
M
D000818:Animals; D015519:Bone Density; D002146:Bony Callus / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000175:diagnosis* / Q000378:metabolism / Q000601:surgery; D005500:Follow-Up Studies; D005594:Fracture Fixation, Intramedullary; D017102:Fracture Healing / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D011859:Radiography