• Sjoerd Rutten, Peter A Nolte, Clara M Korstjens, Marion A van Duin, and Jenneke Klein-Nulend.
• Department of Oral Cell Biology, ACTA-Universiteit van Amsterdam and Vrije Universiteit, Research Institute MOVE, Amsterdam, The Netherlands.
• Bone. 2008 Aug 1; 43 (2): 348-54.

IntroductionLow-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 parameters.Materials And MethodsBiopsies 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).ResultsIn 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.ConclusionsOur 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.

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