Optimal fracture treatment requires knowledge of the complex physiological process of bone healing. The course of bone healing is mainly influenced by fracture fixation stability (biomechanics) and the blood supply to the healing site (revascularization after trauma). The repair process proceeds via a characteristic sequence of events, described as the inflammatory, repair and remodeling phases. An inflammatory reaction involving immune cells and molecular factors is activated immediately in response to tissue damage and is thought to initiate the repair cascade. Immune cells also have a major role in the repair phase, exhibiting important crosstalk with bone cells. After bony bridging of the fragments, a slow remodeling process eventually leads to the reconstitution of the original bone structure. Systemic inflammation, as observed in patients with rheumatoid arthritis, diabetes mellitus, multiple trauma or sepsis, can increase fracture healing time and the rate of complications, including non-unions. In addition, evidence suggests that insufficient biomechanical conditions within the fracture zone can influence early local inflammation and impair bone healing. In this Review, we discuss the main factors that influence fracture healing, with particular emphasis on the role of inflammation.

Good correlation was found with Nachemson's data during many exercises, with the exception of the comparison of standing and sitting or of the various lying positions. Notwithstanding the limitations related to the single-subject design of this study, these differences may be explained by the different transducers used. It can be cautiously concluded that the intradiscal pressure during sitting may in fact be less than that in erect standing, that muscle activity increases pressure, that constantly changing position is important to promote flow of fluid (nutrition) to the disc, and that many of the physiotherapy methods studied are valid, but a number of them should be re-evaluated.

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Flexible fixation of fractures with minimally invasive surgical techniques has become increasingly popular. Such techniques can lead to relatively large fracture gaps (larger than 5 mm) and considerable interfragmentary movements (0.2-5 mm). We investigated the influence of the size of the fracture gap, interfragmentary movement, and interfragmentary strain on the quality of fracture healing. A simple diaphyseal long-bone fracture was modeled by means of a transverse osteotomy of the right metatarsus in sheep. In 42 sheep, the metatarsus was stabilized with a custom-made external ring fixator that was adjustable for gap size and axial interfragmentary movement. The sheep were randomly divided into six groups with three different gap sizes (1, 2, or 6 mm) and small or large interfragmentary strain (approximately 7 or 31%). The movement of the fracture gap was monitored telemetrically by a displacement transducer attached to the fixator. After 9 weeks of healing, the explanted metatarsus was evaluated mechanically in a three-point bending test to determine bending stiffness and was radiographed to measure the amount of periosteal callus formation. Increased size of the gap (from 1 to 6 mm) resulted in a significant reduction in the bending stiffness of the healed bones. Larger interfragmentary movements and strains (31 compared with 7%) stimulated larger callus formation for small gaps (1-2 mm) but not for larger gaps (approximately 6 mm). The treatment of simple diaphyseal fractures with flexible fixation can be improved by careful reduction of the fracture; this prevents large interfragmentary gaps. The experimental fracture model for the metatarsus showed that the healing process was inferior when the gap was larger than 2 mm.

Based on the biomechanical similarities of sheep and human spines demonstrated in this study, it appears that the use of the sheep spine, which already includes evaluation of surgical techniques and bone healing processes, might be extended to spinal implants.

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