A Closer Look At The Potential Of Bone Lengthening Distraction Osteogenesis

Bone lengthening techniques have advanced significantly in recent years. Accordingly, these authors discuss the fundamentals of distraction osteogenesis, including surgical techniques, the expression of growth factors and bone morphogenetic proteins, and common complications in an attempt to improve the understanding of the potential of bone lengthening.

Since Ilizarov, significant strides have occurred in furthering the understanding of both the biology and technique of distraction osteogenesis, a term that describes the de novo production of bone between corticotomy surfaces during gradual distraction.¹ Surgeons have applied these principles to the foot and ankle in addressing osseous deformities such as brachymetatarsia, malunion, non-union, limb length discrepancy and revision surgery.

The foundation of successful iatrogenic new bone formation requires an adequate osteotomy method in which there is careful bone separation, creation of vascular bone surfaces, preservation of the periosteum and prevention of thermal necrosis.^1-3 One of the core tenets of Ilizarov’s technique is the use of a percutaneous corticotomy over an osteotomy in preserving the blood supply of the marrow and periosteum. By definition, a corticotomy involves the transection of only bone cortices, leaving the endosteal (marrow) tissue intact.

An osteotomy is the complete division of the bone including both cortices and endosteal tissue. The use of a corticotomy instead of an osteotomy emphasizes the importance of the blood supply to osteogenesis.^4,5 One can preserve both the periosteal and medullary blood supplies by cutting only the cortex.

Another common technique involves making a corticotomy by transecting approximately two-thirds of the cortex and inserting an osteotome into the remaining corticotomy site and rotating it 90 degrees until the remaining cortex fractures.^4,6

What Is The Best Location To Divide The Bone?
Although the choice of the osteotomy site ultimately relies on the localization of the deformity, one should also take into consideration the pathological and histological characteristics of metaphyseal and diaphyseal bone. Metaphyseal bone is more vascularized, has a larger cross-section providing better stability and possesses thinner cortices, which are easier to separate.

However, the location of this bone leaves little room for fixation. Surgeons should perform metaphyseal osteotomies when addressing juxta-articular deformities or when doing straight lengthening. On the contrary, diaphyseal bone allows more room for fixation but has a smaller cross-section and is less bioactive. Indications for diaphyseal osteotomies should be limited to addressing only diaphyseal deformities.^7,8,9

Current Insights On Techniques In Bone Cutting
When it comes to performing osteotomies with bone lengthening, three common techniques can ensure appropriate lengthening and adequate consolidation.

The classic Ilizarov corticotomy is a percutaneous subperiosteal cortical osteotomy that surgeons often employ due to its preservation of endosteal tissues and vasculature, resulting in more rapid and reliable bone formation. One would execute this through a small periosteal incision and subsequently elevate it with a thin periosteal elevator to create a tunnel for the insertion of an osteotome. Insert the osteotome vertically or parallel to the long axis of the bone to allow for easy passage under the periosteum and then rotate it 90 degrees to a horizontal position. Perform this same periosteal elevation and osteotome insertion technique in both the medial and lateral cortices until the posterior cortex breaks.

The second technique one can employ in bone lengthening is a multiple drill hole osteotomy. Depending on the width of the cortex of the bone, the surgeon can use a drill or a K-wire to drill multiple orthogonal holes in the bone at the level of the intended osteotomy. Proceed to pass an osteotome horizontally across the tunnels created by the drill and rotate it 90 degrees to the vertical position with the purpose of breaking the far cortex.

Surgeons most often utilize a Gigli saw osteotomy in the foot as multiple osteotomies are frequently necessary in bones that are in close proximity to one another. This technique allows for a clean, transverse cut that does not require osteoclasis. The surgeon must be cognitive of the risk of neurovascular injury. Do not pass this Gigli saw through diaphyseal bone as it creates extended bone healing times. Pass a suture subperiosteally across the intended bones(s) by creating a tunnel with a series of straight and curved hemostats. Then tie the suture to one end of the Gigli saw and pull it through the created tunnel subperiosteally. This allows for the Gigli saw to be deep to any neurovascular structures, therefore avoiding any soft tissue or neurovascular injury. Place the handles on the Gigli saw and advance them across the intended bone(s) in a uniform, symmetrical manner in an attempt to remain perpendicular to the long axis of the bone(s).^4,6,9

Frierson and colleagues conducted a study in 1994 on 15 hindlimbs of adult dogs comparing the efficacy of these corticotomy techniques in distraction osteogenesis via Ilizarov bone lengthening.⁶ The results demonstrated no histological, density or perfusion differences between the bone regeneration in dogs that had a corticotomy with osteoclasis and the bone regeneration in dogs that had an osteotomy with multiple drill holes. However, an increased rate of delayed consolidation occurred in the group that had an osteotomy with an oscillating saw. The authors proposed that this was secondary to the increased thermal necrosis produced by the power (oscillating) saw.

What You Should Know About Distraction Osteogenesis
Distraction osteogenesis is a surgical technique consisting of a controlled osteotomy followed by gradual and controlled distraction of the two bone ends utilizing a mechanical stretch of the vascularized bone surfaces to stimulate new bone.^4,10 This technique involves several temporal phases that are each responsible for the induction, formation and consolidation of new bone between distracted fragments.

The latency phase starts immediately following the osteotomy and lasts between five and seven days. This stage resembles the acute stage of fracture repair with the formation of hematoma, inflammatory response and subsequent differentiation of stem cells into chondrocytes and osteoblasts.⁸ Pro-inflammatory cytokines interleukin-1 and 6 (IL-1 and IL-6), which are involved in bone repair, upregulate in this phase in order to promote periosteal callus formation. The expression of tumor necrosis factor (TNF) and recruitment of mesenchymal stem cells in the latency period supplements the organization and recruitment of inflammatory and mesenchymal cells as the bone segments prepare for distraction. An abbreviated form of this latency phase will risk the lack of bone formation and a prolonged phase can result in premature consolidation.¹¹

Following the latency period is the distraction phase. Distraction of the two bone segments starts at a specific rate and rhythm, typically at 1.0 mm a day, divided into four increments. Although 1 mm/day is classically cited, in practice the rate of distraction varies depending on multiple factors (patient age, health, medications, location of osteotomy, the type of osteotomy performed, etc.). In the foot and ankle, the distraction rate can range from 0.5 mm/day to 1 mm/day. The distraction phase consists of resorption of the periosteal callus and the formation of a fibrous interzone, comprised of types 1, 2, 4 and 10 collagen, oriented parallel to the distraction force.¹²

Probably the most distinguishing feature of the distraction phase involves the presence of angiogenesis and neoangiogenesis, regulated by the expression of vascular endothelial growth factor (VEGF) and angiopoietin signaling pathways.¹¹ New blood vessels grow in loops along and between the collagen fibers, and allow osteoblasts to be recruited to the area. This fibrous interzone thus acts as a scaffold for the new bone formation, which forms by intramembranous ossification whereby bone forms directly from osteoblasts.

This is in distinct contrast to fracture healing whereby bone forms primarily by endochondral ossification using a cartilage template. In various animal models, researchers have shown that the expression of numerous growth factors related to osteogenesis and chondrogenesis upregulate, thus driving the process of intramembranous ossification.^13,14 These include bone morphogenetic proteins (BMP-2, BMP-4), and growth factors including transforming growth factor beta (TGF-beta), fibroblast growth factor (FGF), insulin growth factor (IGF) and platelet derived growth factor (PDGF).

Once you have achieved the desired amount of lengthening, the distraction phase stops and the consolidation phase begins. During the consolidation phase, osteoid (unmineralized bone matrix) that osteoblasts laid down becomes progressively mineralized. An increase in the expression of TNF-alpha regulates consolidation and the downregulation of BMP expression.¹¹ TNF-alpha controls remodeling of the regenerated bone by coordinating the coupled action of osteoclasts and osteoblasts. This is the longest phase in distraction osteogenesis, allowing approximately one month for each centimeter lengthened.⁴ Methods of bone separation that disrupt the periosteum, such as significantly displaced corticotomies or osteotomies, can result in decreased osteogenesis.¹⁵

In daily clinical use, we consider consolidation achieved when there is tricortical radiographic consolidation on two orthogonal radiographs. In foot and ankle cases, a CAT scan may be necessary to confirm complete osseous healing. Obtaining this endpoint allows for removal of the external fixation.

Key Insights On Distraction Rate And Rhythm
The effect of the rate and rhythm for distraction osteogenesis has a significant effect on the expression of factors involved in the distraction osteogenesis process. Schiller and coworkers examined the alteration of expression of various growth factors in rapid distraction in comparison to routine distraction.¹³ Furthermore, several experimental studies have shown improved bone regeneration using continuous versus intermittent distraction osteogenesis with the former demonstrating upregulation of several growth-stimulating genes.¹⁶ Schiller and coworkers found there was decreased cellular staining of fibroblast growth factor, vascular endothelial growth factor, and platelet-derived growth factor in the rapid distraction group starting on the first day of lengthening.¹³

There are numeric parameters to quantify the quality and speed of bone formation. Authors most widely use the healing index parameter and define it as the time needed for consolidation per centimeter of the distracted osteotomy site.¹⁵ Consolidation time is defined as the time between the end of distraction and total consolidation or removal of hardware. The consolidation time is about twice as long as the distraction time in children but may be three to four times longer in adults.¹⁵ Accordingly, it usually amounts to one month/cm in children and two to three months/cm in adults.¹⁷

What Are The Effects Of Bone Lengthening On Surrounding Tissues?
Neurovascular compromise is less of a concern than musculotendinous injury during the process of gradual bone lengthening. Nerves and vessels are able to adapt in length during the distraction process and recover from temporary degenerative changes within two months after distraction has ceased.^4,5

Neurovascular compromise is most often the result of surgical technique, such as pin placement, significant edema and/or compartment syndrome. More commonly, bone distraction places increased tension on the muscles as the muscle length becomes relatively short in comparison to bone, ultimately leading to muscle contractures. The muscles most frequently involved in contracture are those that cross two joints and are a result of an imbalance between the strength of the flexors and the extensors.¹¹ The mechanism of action of muscle groups can also be inhibited secondary to transfixation of the tendons or fascia via external hardware (i.e. pins, K-wires).

Combating The Complications Of Distraction Osteogenesis
In addition to the previously mentioned neurovascular and musculoskeletal complications, one of the major drawbacks of distraction osteogenesis is the prolonged length of time needed to reach consolidation. This extended period of time in which the external fixator remains intact may increase the risk of complications, such as pin site infections, pain, discomfort and psychological complications.⁵ There are numerous methods to accelerate the consolidation time, including the effect of mechanical loading induced by early weightbearing.^14,18

Other reported complications in distraction osteogenesis include joint stiffness and subluxation as well as axial deviation.^1,4,5 During the lengthening process, there is a tendency for the bone segment being lengthened to gradually veer off its intended course due to muscle imbalance or instability secondary to an inadequate external fixator construct.

Other complications one may encounter are related to the rate of consolidation at the distraction site. Premature consolidation occurs as a direct result of an excessive latency period in which significant callus healing blocks the distraction of the osteotomy site. In contrast to premature consolidation, prolonged or delayed consolidation can occur secondary to technical factors including a traumatic corticotomy, initial diastasis or rapid distraction.^4,5 Authors have also reported pin site tract infections, fracture after removal of an external fixator and chronic regional pain syndrome.¹¹

In Conclusion
When it comes to techniques in bone lengthening, there has been significant evolution over the past century although the basic principles introduced by Ilizarov remain the foundation. While researchers continue to report numerous potential complications, most are easily treatable during the treatment and do not affect the goal and final outcome. In a study conducted by Velazquez and colleagues in 1993, the authors demonstrated a complication rate of 69 percent following bone lengthening procedures that were performed in the first six-month period of experience but only a 35 percent complication rate in an 18-month period.¹¹ Accordingly, distraction osteogenesis has become a viable treatment option in the foot and ankle when performed by a surgeon with an appropriate level of training and expertise.

Dr. Lamm is the Head of Foot and Ankle Surgery at the International Center for Limb Lengthening, and the Director of the Foot and Ankle Deformity Correction Fellowship at the Rubin Institute for Advanced Orthopedics at the Sinai Hospital in Baltimore. He is the Chief of Limb Preservation and the Co-Director of the Veterans Affairs/Sinai Podiatric Surgical Residency at the Sinai Hospital. He is a Professor and the Rotation Director for the Podiatric Residency at Harvard Medical School. Dr. Lamm is a Fellow of the American College of Foot and Ankle Surgeons. He also is an editor for the Journal of Foot and Ankle Surgery, and serves on the PRESENT Podiatry Advisory Board.

Dr. Knight is a Foot and Ankle Deformity Correction Fellow at the Rubin Institute for Advanced Orthopedics at the Sinai Hospital in Baltimore. She is also an Associate of the American College of Foot and Ankle Surgeons.

Dr. Kelley is an Assistant Professor of Paediatric Orthopaedic Surgery at The Hospital for Sick Children in Toronto. He specializes in limb lengthening and deformity correction surgery. Dr. Kelley is also a PhD Candidate in the Department of Developmental and Stem Cell Biology in the field of bone regeneration and repair at the Research Institute at the Hospital for Sick Children.

References

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