Low-intensity pulsed ultrasound (LIPUS) accelerates impaired fracture healing, but the exact mechanism is
unknown. The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed
union of the osteotomized fibula, by using histology and histomorphometric analysis to determine bone formation and bone resorption
Materials and methods
Biopsies were obtained from 13 patients (9 female, 4 male; age 42-63) with
a delayed union of the osteotomized fibula after a high tibial osteotomy, treated for 2-4 months with or without LIPUS in
a randomized prospective double-blind placebo-controlled trial. In the histological sections of the delayed union biopsies,
3 areas of interest were distinguished, i.e. 1) area of new bone formation at the fracture ends, 2) area of cancellous bone,
and 3) area of cortical bone. Histomorphometrical analysis was performed to determine bone formation and bone resorption parameters
(as well as angiogenesis).
In LIPUS-treated delayed unions, endosteal callus formation by direct bone
formation without a cartilage intermediate as well as indirect bone formation was observed, while in untreated controls only
indirect bone formation was observed. In the area of new bone formation, LIPUS significantly increased osteoid thickness by
47%, mineral apposition rate by 27%, and bone volume by 33%. No increase in the number of blood vessels was seen in the newly
formed bony callus. In the area of cancellous bone, bone volume was significantly increased by 17% whereas no effect on osteoid
thickness and mineral apposition rate was seen. LIPUS did not affect osteoid volume, osteoid maturation time, number of osteocytes,
osteocyte lacunae, or osteoclast-like cells in any of the areas of interest.
Our results suggest
that LIPUS accelerates clinical fracture healing of delayed unions of the fibula by increasing osteoid thickness, mineral
apposition rate, and bone volume, indicating increased osteoblast activity, at the front of new bony callus formation. Improved
stability and/or increased blood flow, but probably not increased angiogenesis, might explain the differences in ossification
modes between LIPUS-treated delayed unions and untreated controls.
Keywords: Fracture healing; Delayed union; Low-intensity
pulsed ultrasound; Bone histomorphometry; Osteoblast activity