The effect of altering the mechanical loading environment on the expression of bone regenerating molecules in cases of distraction osteogenesis

Abstract

Distraction osteogenesis (DO) is a surgical technique where gradual and controlled separation of two bony fragments following an osteotomy leads to the induction of new bone formation in the distracted gap. DO is used for limb lengthening, correction of bony deformities, and the replacement of bone loss secondary to infection, trauma, and tumors. Although DO gives satisfactory results in most cases, one major drawback of this technique is the prolonged period of time the external fixator has to be kept on until the newly formed bone consolidates thus leading to numerous complications. Numerous attempts at accelerating bone formation during DO have been reported. One specific approach is manipulation of the mechanical environment during DO by applying changes in the standard protocol of distraction. Attempts at changing this mechanical environment led to mixed results. Increasing the rate or applying acute distraction, led to poor bone formation in the distracted zone. On the other hand, the addition of compressive forces (such as weight bearing, alternating distraction with compression or by over-lengthening, and then shortening) has been reported to increase bone formation. It still remains unclear why these alterations may lead to changes in bone formation. While the cellular and molecular changes occurring during the standard DO protocol, specifically increased expression of transforming growth factor-β1, platelet-derived growth factor, insulin-like growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and bone morphogenic proteins have been extensively investigated, the literature is sparse on the changes occurring when this protocol is altered. It is the purpose of this article to review the pertinent literature on the changes in the expression of various proteins and molecules as a result of changes in the mechanical loading technique in DO and try to define potential future research directions.

Keywords: bone regenerating molecule; bone regeneration; distraction osteogensis; growth factor; mechanical loading.

Figure 1

(A) Application of distractor; (B) start of distraction; (C) end of distraction; (D,E) consolidation phase without any distraction until bone in the distraction gap consolidates; (F) removal of distractor. ©2012 Hamdy et al. (7).

Figure 2

Cellular changes in a rabbit DO model during distraction osteogenesis of the tibia (stain is Trichrome staining). The numbers indicate the number of weeks after the distraction process was started (1–3 are during the distraction phase and 4–6 are during the consolidation phase). Co, cortex; LZ, lengthened zone; Ca, callus; FIZ, fibrous interzone. Bar scale = 2 mm. Reprinted from Rauch et al. (34), with permission from Elsevier.

Figure 3

Distraction osteogenesis is used to manage multiple orthopedic conditions including congenital short femur (A) and fibular hemimelia (B).

Figure 4

Ilizarov ring fixator frame applied for distraction osteogenensis of the femur.

Figure 5

(1) Standard DO: 0.25 mm/6 h to achieve 1 mm/24 h; (2) continuous DO: 0.02 mm/24 min to achieve 1 mm/24 h; (3) accordion maneuver: addition of compression to the standard distraction; (4) accelerated DO: 1.5 mm/24 h; (5) highly accelerated DO: 3 mm/24 h. (A) Normal callus formation; (B) abnormal callus formation. Based on Ref. (–26).

Figure 6

Bone morphogenic protein pathway. BMP; bone morphogenic protein, NBP; nuclear binding protein.

Figure 7

Diagram showing the process of osteogenesis by different mechanical environments. Adopted from Chao and Inoue (75).