Craniofacial Distraction Osteogenesis

Article Author:
Sabrina Brody-Camp
Article Editor:
Ryan Winters
Updated:
7/15/2020 1:34:44 AM
PubMed Link:
Craniofacial Distraction Osteogenesis

Introduction

Distraction osteogenesis describes the new growth of bone created by gradually separating two bony surfaces after an osteotomy. Initially described in the mandible in Germany in the 1930s, the technique takes advantage of the sequence of events during normal osteogenesis after any bony injury; the initial injury site initially develops a fibrous callus, which subsequently ossifies.[1]

If the fracture is not immobilized, this ossification will not complete and a fibrous union results. While this is undesirable after an accidental fracture (the basis for casting or other rigid fixation after fractures), the intentional movement of an osteotomy along a controlled vector gradually stretches this fibrous callus, which is subsequently immobilized allowing ossification. The net result is a lengthening of the bone at the site of the osteotomy. This technique has become widely used for malformations of the cranial skeleton and is used to elongate the mandible, midface, and calvarium. The advantages of the approach are its creation of strong bone in a controlled manner, resistance to relapse, and adaptive changes of the soft tissue envelope.

Craniofacial distraction osteogenesis has proven extremely successful in treating a variety of both non-syndromic and syndromic patients with craniofacial abnormalities, providing both a cosmetic and functional result that is superior when compared to other techniques.[2][3]

Anatomy and Physiology

Normal Craniofacial Development

As an infant grows into childhood and adulthood, the craniofacial proportions change. To illustrate how normal growth occurs, the craniofacial region is broken up into three general regions: the neurocranium (further divided into the calvaria and basicranium), the nasomaxillary complex, and the mandible. In infants, the neurocranium is much larger relative to the nasomaxillary complex and the mandible. As demand for the masticatory and respiratory systems grows, the nose, mouth, and mandible grow considerably to more closely resemble the proportions of the adult face.

The calvaria forms the roof of the skull, while the basicranium forms the floor. The bones of the calvaria are initially separated by soft fontanelles, which will eventually form sutures and fuse in the adult. As the brain grows, the calvarial bones slowly separate from one another, stimulating new bone growth. The calvaria is fully formed by about four years of age. Craniosynostosis results when the fusion of the calvarial sutures occurs too early. The basicranium grows more slowly than the calvaria; it reaches 95% of its adult size by the age of 10.[4]

The nasomaxillary complex normally grows anterior and inferiorly from the basicranium as a result of soft-tissue growth. Midface maturity is reached at about 12 years. As the nasomaxillary complex grows, the mandible concomitantly protrudes in the downward and forward directions. This results from the increasing size of the muscles of mastication and the developing oropharynx. The mandible does not reach adult size in males until well after puberty, into their early twenties.[5]

Osteogenesis

Osteogenesis occurs by the initial formation of primary bone. Primary bone is immature and lacks strength; its collagen fibers are arranged in a random pattern. Primary bone is gradually replaced by stronger secondary bone, which has an orderly collagen pattern. Osteogenesis can occur either through endochondral ossification of existing cartilage or intramembranous ossification in the mesenchyme. The latter is employed in distraction osteogenesis: undifferentiated mesenchymal cells are signaled to differentiate into osteoblasts, which create the osteoid of primary bone. This ossifies to become secondary bone.

Osteogenesis in Fracture Healing

There are three stages to fracture healing: inflammation, repair, and remodeling.

Inflammation Stage: A hematoma forms at the fracture site and growth factors are secreted by hematopoietic cells in the hematoma. Fibroblasts migrate to the fracture site in response to transforming growth factor-beta (TGF-Beta) and other cytokines and granulation tissue forms at the fracture site. Fibroblasts and osteoblasts then proliferate at the fracture site.

Repair Stage: Formation of the primary soft callus begins. Ossification occurs as fibroblasts differentiate into chondrocytes expressing type 2 collagen, which are gradually replaced with type 1 collagen (woven bone). This process is dependent upon many cytokines, particularly tumor necrosis factor-alpha (TNF-Alpha). This is the stage utilized by distraction osteogenesis. The initial soft callus is allowed to form, and then a mechanical force is applied to stretch the callus without breaking it, resulting in lengthening. Rates of distraction (stretch) tolerated depend on the age and health of the patient and of the bones being distracted. A rate of 1mm/day is frequently employed in mandibular distraction, for example. The maximum distance a bone can be distracted also differs according to the bone involved but is usually constrained most by the surrounding skin and soft tissue. If a callus is immobilized fracture healing will proceed to the remodeling stage, ergo, once the desired length of distraction has been achieved, the bone segments must be held in rigid fixation to allow ossification and subsequent remodeling.[6]

Remodeling Stage: Chondrocytes present undergo terminal differentiation involving numerous signaling pathways, some involving parathyroid hormone-related peptide (PTHrP) and bone morphogenetic protein (BMP). The extracellular matrix becomes calcified, and type X collagen is expressed as chondrocytes undergo apoptosis. New blood vessel ingrowth is stimulated by vascular endothelial growth factor (VEGF), and the resultant woven bone enters organized osteoblast/osteoclast remodeling.[7]

Indications

Regardless of the anatomic site, the goal of distraction osteogenesis is to elongate the chosen bone in order to restore more normal anatomic function.[2]

Mandibular Hypoplasia/Pierre Robin Sequence: Neonates may present with airway obstruction secondary to mandibular hypoplasia. Pierre Robin sequence (PRS) describes a triad of micrognathia in conjunction with glossoptosis and cleft palate. These patients will often have feeding difficulty in addition to intermittent upper airway obstruction due to retrodisplacement of the tongue. When conservative measures have failed (prone positioning, nasopharyngeal airway, tongue-lip adhesion, etc.) mandibular distraction osteogenesis has provided a viable alternative to tracheostomy placement. Distraction can also be used in a vertical vector to increase the height of the mandibular ramus as a component of craniofacial microsomia, for example.[8]

Midface Hypoplasia: Midface hypoplasia can present as a result of several craniofacial syndromes (Treacher Collins, Cohen syndrome, etc.) and in patients with isolated cleft lip or palate. Patients will often have visible malar retrusion, class 3 malocclusion, and a degree of exorbitism due to isolated retrodisplacement of the inferior orbital rim. Similar to mandibular hypoplasia, patients may present with airway obstruction or severe sleep apnea. Distraction osteogenesis has proven a useful tool in correcting these abnormalities.[9]

Craniosynostosis: Craniosynostosis describes the premature fusion of calvarial suture lines. Left untreated, the condition can result in severe craniofacial deformity, intracranial hypertension, cognitive impairment, developmental delay, seizures, blindness, and death. Distraction osteogenesis provides an alternative to traditional surgery for single or multisuture craniosynostosis. This can be used to expand the anterior, or more commonly, the posterior cranial vault. Increasing the size of the cranial vault provides relief of the increased intracranial pressure caused by craniosynostosis.[2][10]

Contraindications

Patients who are not surgical candidates due to concurrent medical problems should avoid craniofacial distraction osteogenesis. If conservative measures are well tolerated and alleviate the afflicting condition, then they should be used in preference to surgical management, especially in young children. Positional plagiocephaly must be differentiated from true craniosynostosis, as the former is managed exclusively non-surgically.

Equipment

There are two categories of devices: internal and external, and there are several different device manufacturers worldwide.

Internal devices are entirely implanted and affixed directly to the bone with screws, and exist as both linear (straight-line vector of distraction) and curvilinear (curved arc of distraction). There is an activator that is externalized and used to increase the distraction gap. Some surgeons feel there is a greater transmission of the distraction forces to the bone segments because the device is directly adherent to the bones, yielding a more predictable distraction. These devices may also be more aesthetically acceptable to parents and families during the distraction and consolidation periods. They are removed in a second procedure once the consolidation phase is complete.

External devices rely on titanium pins or wires that are implanted percutaneously to both the proximal and distal bone segments, and the distractor device attaches externally to the skin to these implanted pins. These also exist as both linear and multi-vector devices. The external devices were developed first, and so have the longest-term outcomes data available regarding their use. Some surgeons feel the distraction forces are not as efficiently transmitted with external devices, with some force transmission being lost due to flexion of the pins. External distraction can facilitate multi-vector distraction and allow for correction of asymmetries by adjusting the distraction vectors during the treatment period, which is not possible with implanted devices. Once consolidation is complete, the pins are removed in a minor procedure; a second open surgery is not required.

Personnel

Distraction osteogenesis is performed under general anesthesia, requiring a surgeon, anesthetist, nurse, and is greatly facilitated by a surgical assistant.

Preparation

Some surgeons will obtain preoperative virtual surgical plans. This technique requires high-resolution preoperative computed tomography and 3D modeling and computer-assisted drafting (CAD)-based software proprietary to the distractor device manufacturers. This allows the proposed operation to be performed "virtually" on the computer to better predict and visualize the desired final bone positions. Appropriately sized and/or angled distractor devices can then be selected preoperatively, and 3D printed models can be obtained, and any plates or devices can be preoperatively custom-bent based on these models. This service may not be available in all locations and does significantly increase the overall cost.[11]

Technique

Craniofacial osteogenesis can be divided into four phases:

Initial Osteotomy/Distractor Placement: Surgery is required to create an osteotomy in the desired bone and to place the distractor devices. Occasionally an osteotomy does not need to be made as an existing suture line can be used (cranial vault distraction, rapid palate expansion). Distraction will occur in a plane perpendicular to that of the osteotomy. Once the osteotomy has been performed, the device is attached and tested under direct visualization to ensure unrestricted movement of the bony segments. Distractors can be either internal or external, depending on the anatomic site and goals of surgery, as discussed above.[2]

Latency Phase: After osteotomy and device placement, the device is not activated for a period of 24 hours to five days, depending on the site of the desired distraction. This latency period allows for bone healing to begin by way of the formation of a soft callus.

Active Distraction Phase: Over a period of days to weeks, the distraction device is slowly activated, usually once or twice daily. This process provides incremental traction on the bony callus, leading to osteogenesis. This phase is continued until the desired lengthening is achieved, often with a degree of overcorrection to account for some relapse.

Consolidation Phase: The distractor is left in place for several weeks following a distraction. During this time period, the immature primary bone created will mineralize, and eventually resemble mature secondary bone. The immobile distractor provides rigid fixation of the bony segments, allowing bony remodeling to continue and maturation into the ossified bone. After the consolidation phase, the device is removed.[3]

Mandibular Distraction: The most common indication for mandibular distraction is lengthening of the mandibular body in neonates and children with airway compromise due to severe micrognathia or retrognathia. For this indication, the osteotomy should be placed at the junction of the mandibular body and angle to avoid injury to tooth buds. The lateral, superior, and inferior cortices of the mandible are cut (both traditional saws and piezo-electric/ultrasonic cutters can be used), and a bone spreader is used to fracture and release the posterior cortex. This is to avoid injury to the inferior alveolar neurovascular bundle in its canal. The osteotomy can be made via and intra-oral, extra-oral, or combined approach. The desired device is then affixed to the bone segments proximally and distally and tested to ensure free mobility across the osteotomy.

Preoperative assessment of the relationship of the maxillary and mandibular alveolar arches allows measurement of the discrepancy; when calculating the distance to be distracted, plan for significant overcorrection. The goal should be at least end-to-end occlusion of the arches, though outright over projection of the mandibular alveolar arch is desirable, as significant relapse occurs after mandibular distraction in this vector. The latency phase for neonatal mandibular distraction is 24 hours, and the neonatal mandible can be distracted at a rate of 1 to 2 mm/day. It is practically very difficult to distract more than 20 mm in a neonatal mandible due to soft-tissue constraints. The consolidation phase lasts 4-6 weeks, and then the devices are removed.[12]

Midfacial Distraction: Distraction osteogenesis can be used for LeFort advancements as well as monobloc advancements, and both internal and external devices exist. For LeFort 1 advancements, intraoral incisions are planned via a midfacial degloving approach. The osteotomies are made horizontally across the inferior face of the maxilla, taking care not to injure the tooth roots. The maxillary crest is separated from the inferior nasal septum, and the pterygoid plates are separated from the maxilla with an osteotome. Preoperative cephalometry calculations determine the degree of advancement required (virtual surgical planning can also be used). The distractor is then affixed and tested to ensure the unimpinged motion of the maxilla. The consolidation period is five days, and the rate of distraction is 1 mm/day. Internal devices are used for LeFort 1 advancement almost exclusively, and the consolidation phase lasts eight weeks, at which point the devices can be removed.[13] 

LeFort 3 and monobloc advancements require a bicoronal incision, which is then extended down over the nasofrontal suture, superior and lateral orbital rims, and zygomatic arches. For LeFort 3 advancement, osteotomies include an osteotomy at the nasofrontal suture extended laterally and inferiorly along the medial and inferior orbital walls. This is extended through the lateral orbital rim. An osteotomy is then made through the zygomatic arch. An osteotomy must then be made through the pterygoid plates intraorally, as in a LeFort 1, and an osteotomy is made through the nasal septum. This mobilizes the entire midface, separating it from the anterior skull base. Internal and external devices are both routinely used. Internal devices are affixed to the zygomatic arch/orbital rim junction on the midface and the temporal bone.

External devices use brackets or circum-zygomatic wires that are brought out percutaneously through the anterior cheek skin. These are joined to an external halo device, which is firmly anchored percutaneously to the temporoparietal skull. With the devices attached, a test should be performed to ensure no impingement is present, and the mobile midface does indeed move. The consolidation period is five days, and the rate of distraction is 1 mm/day. Internal devices are used for LeFort 1 advancement almost exclusively, and the consolidation phase lasts eight weeks, at which point the devices can be removed.

Cranial Vault Distraction: Distraction osteogenesis can be utilized to expand the cranial vault in patients with craniosynostosis. It is most useful in patients with single or dual suture synostosis, while multi-suture or pan-suture synostosis will typically require formal total cranial vault remodeling. Additionally, distraction is not often used for metopic synostosis as significant re-shaping of the frontal bones, and orbital advancement is often required concurrently. The incision will depend on the suture involved, though a bicoronal incision is standard unless a minimally-invasive approach is used for a strip craniectomy. Once the synostotic suture is exposed, burr holes are made, and the dura released from the intracranial surface with gentle dissection with Woodson elevators. The osteotomy is then made across the synostotic suture. Internal distraction devices are used almost universally for cranial vault distraction. The device is applied and tested to ensure mobility. The latency period ranges from five days in young children (under two years old) to 10 days (16 years and older). The rate of distraction is 1 mm/day in young children and 0.5 mm/day in teens/adults, and the consolidation phase is eight weeks.

A more common, and more involved, variant is posterior cranial vault distraction. This is employed in craniosynostosis or other conditions that increase intracranial pressure, but where frontocranial distraction is not possible or has failed. Such anterior distraction is inherently limited by the position of the eyes. Posterior cranial vault distraction creates osteotomies that do not correspond exactly to an anatomic suture. It is a coronal osteotomy beginning in the posterior aspect of the parietal bone, extending from the sagittal suture to the anion, then directed infero-posteriorly to the inion. This releases the posterior skull, and multiple distractor devices are then placed (usually two or three devices are used) as described above. The parameters of distraction are the same as above. Utilizing this technique, the intracranial volume can be expanded by as much as 35%.[14]

Complications

Complications From Distraction Osteogenesis

Relapse: Some degree of relapse is likely to occur with any distraction osteogenesis, especially that of the mandible. However, overcorrection of 10 to 30% depending on the anatomic site will often account for the expected degree of relapse and yield a good clinical result.

Device Failure: This is defined as occurring when the device itself breaks and is relatively uncommon. There are different rates published in the literature, and they are slightly different according to the location of distraction. The highest rates of device failure ar in mandibular distraction, but even then, they are near 1%.

Device Extrusion: This is a rare complication where the device extrudes through the skin, migrating through the bone rather than moving the bone itself. This is a manifestation of orthodontic, rather than the desired orthopedic forces. The root cause is the impingement of the bony segments or other reasons that the bones cannot move freely in the desired vector. It is essential to test the mobility of the segments in relation to the osteotomy under direct, intraoperative, visualization to ensure they are free to move in the desired vector.

Injury to Tooth Buds: This is principally encountered in mandibular distraction osteogenesis, though it can occur in the maxilla as well. This can be avoided with careful preoperative planning based on preoperative planning, careful placement of osteotomies as far (dentally) distally as possible, and avoidance can potentially be enhanced via 3D imaging and virtual surgical planning, allowing for optimization of the osteotomy site.

Nerve Injury: The inferior alveolar nerve, branches of the facial nerve, as well as the supraorbital and infraorbital nerves, are at risk of injury depending on the approach used and the bone to be distracted. Care with the plane of dissection, as well as the location of the osteotomy, will help to avoid nerve injury. The technique described above will minimize the risk of inferior alveolar nerve injury during mandibular distraction. Permanent or severe injuries to the facial nerve are very rare, accounting for <1% of complications of all craniofacial distraction procedures.

Malocclusion: Manipulation of the dentition-bearing bones inherently carries the risk of malocclusion. Even with the use of dental splints, the rate of symptomatic malocclusion is very high in patients undergoing maxillary advancement. Similarly, the future need for orthodontics is very high in patients who have undergone neonatal mandibular distraction. If the patient is to undergo either of these procedures, regardless of age, they should be counseled; they will very likely require orthodontia in the future. Additionally, occlusal complications such as open-bite deformity and temporomandibular joint symptoms may result from suboptimal distraction vectors. Serial radiographs during the active distraction phase help to identify this problem early, when combined with preoperative cephalometric planning. If the occlusal cant is disrupted, this can potentially be corrected if multi-vector, external distractor devices are used.

Cerebrospinal Fluid (CSF) Leak: This is rare, though it can occur with either anterior or posterior cranial vault expansion. Often the leaks are small and can be managed conservatively, either by observation or with the placement of a lumbar drain. The risk of CSF leak is highest in anterior craniofacial (LeFort 2, 3, and monobloc) distraction, though it is reportedly lower than the 10% from standard, open, monobloc advancements. This carries the risk of meningitis also, which is as high as 10% in standard open techniques, and slightly lower when employing distraction techniques.[15] The risk of death is low (less than 10%), though it is significantly lower in monobloc advancement when utilizing distraction as opposed to traditional open techniques.[15]

Scarring: The use of an irregular (sine-wave) or irregularly irregular (random) incision can minimize scar prominence. Incisions should be closed in layers, and electrocautery should be minimized at the scalp surface to avoid the death of hair follicles. Similarly, Rainey clips should be avoided to avoid pressure necrosis of the follicles at the incision edges. There may be some degree of tension present after the cranial vault is reconstructed, which can precipitate hypertrophic scarring. All techniques available should be employed to allow for tension-free closure of the scalp. If scar hypertrophy does occur, this can be treated later with serial excision of the scar. Additionally, particularly with the use of external devices in mandibular distraction, tension-related scars can be problematic between the proximal and distal percutaneous pins. The skin is often the least-forgiving tissue in such cases, and tension-related scars can develop towards the end of mandibular distraction that can be unsightly.

Infection: This is minimized by the use of systemic antibiotics peri-operatively, and topical antibiotics to the incisions postoperatively. In high-risk operations such as LeFort 2, 3, or monobloc advancements, prophylactic postoperative antibiosis is indicated as the untreated meningitis rate approaches 10%. Ceftriaxone is commonly employed, as are other antibiotics that cover skin and hair flora but have good CSF penetration profiles.[2][16][17]

Clinical Significance

Craniofacial distraction osteogenesis can be utilized to help alleviate the effects of cranial malformations. Whether to avoid tracheostomy for upper airway obstruction or to relieve intracranial hypertension caused by craniosynostosis, distraction osteogenesis is widely used in the care of patients with abnormalities of the craniofacial skeleton. 

Mandibular distraction osteogenesis is successful in preventing tracheostomy or allowing decannulation in 97.6% of patients with isolated Piere Robin Sequence, and >90% of syndromic PRS, but is far less successful in patients with concurrent lower airway abnormalities such as tracheomalacia. Some centers will defer mandibular distraction of the mandible until a later age in these patients, as the rate of tracheostomy is similar, whether or not they undergo mandibular distraction.[16][18]

When performed for midface hypoplasia, distraction osteogenesis can greatly improve the sunken-in appearance of the face, protect the eyes from damaging intra-ocular pressures, alleviate intracranial hypertension, as well as successfully treat obstructive sleep apnea. The procedure may increase the success rate of facial advancement surgery when compared to traditional rigid methods and may avoid secondary operations, which are often required for traditional Lefort 3 osteotomies performed in childhood.[9][19]

Cranial vault expansion by distraction osteogenesis may be less technically challenging than traditional single-stage vault expansion surgery, particularly in the posterior cranial vault. It has fewer complications, and grants much greater vault expansion, allowing for successful correction of intracranial hypertension.[10][17]

Enhancing Healthcare Team Outcomes

Patients with craniofacial malformations require workup and treatment by an interdisciplinary team that can include craniofacial surgeons, otolaryngologists, neurosurgeons, ophthalmologists, plastic and reconstructive surgeons, speech and language pathologists, clinical dietitians, dentists, orthodontists, geneticists, and social workers. When considering craniofacial distraction osteogenesis, preoperative workup by the interprofessional team is essential to delivering desired outcomes. Nutritional status should be optimized, and expectations of the patient and family must be managed. Preoperative assessment of the patient's occlusion, cranial shape, and position of the orbits should be performed. Preoperative photographs and imaging studies (including cephalometry, nasometry, high-resolution CT scans, and MRI scans, to name a few). The imaging required will vary depending on the individual patient. High-resolution 3-D computed tomography is especially helpful prior to surgery.[2]

Postoperatively, patients will be admitted to the hospital for several days and may require a period of intensive care immediately postoperatively, particularly those who have undergone LeFort 3 or monobloc advancement, as they require neurologic monitoring and may have lumbar drains. Many mandibular distraction patients may remain intubated during the distraction phase, and a specific airway plan should be in place in case the endotracheal tube becomes dislodged. Nurses taking care of the patients should be made aware of the daily distraction schedule, and what potential complications may arise. They should pre-medicate the patient for pain relief before each distraction activation (often 1 to 2 times per day) and be aware of any local wound care needs for percutaneous devices. Appropriate physical, occupational, and speech therapy should be provided in the postoperative period. Creating a standardized postoperative pathway that involves the entire interprofessional team has been proven to improve patient outcomes.[20] [Level 3]


References

[1] Dennis SC,Berkland CJ,Bonewald LF,Detamore MS, Endochondral ossification for enhancing bone regeneration: converging native extracellular matrix biomaterials and developmental engineering in vivo. Tissue engineering. Part B, Reviews. 2015 Jun     [PubMed PMID: 25336144]
[2] Winters R,Tatum SA, Craniofacial distraction osteogenesis. Facial plastic surgery clinics of North America. 2014 Nov;     [PubMed PMID: 25444735]
[3] Klement KA,Black JS,Denny AD, Versatility of Distraction Osteogenesis for the Craniofacial Skeleton. The Journal of craniofacial surgery. 2016 May;     [PubMed PMID: 26999694]
[4] Madeline LA,Elster AD, Postnatal development of the central skull base: normal variants. Radiology. 1995 Sep;     [PubMed PMID: 7644640]
[5] Akgüner M,Barutçu A,Karaca C, Adolescent growth patterns of the bony and cartilaginous framework of the nose: a cephalometric study. Annals of plastic surgery. 1998 Jul;     [PubMed PMID: 9678471]
[6] Hopper RA,Ettinger RE,Purnell CA,Dover MS,Pereira AR,Tunçbilek G, Thirty Years Later: What Has Craniofacial Distraction Osteogenesis Surgery Replaced? Plastic and reconstructive surgery. 2020 Jun     [PubMed PMID: 32459782]
[7] Shen Z,Lin H,Chen G,Zhang Y,Li Z,Li D,Xie L,Li Y,Huang F,Jiang Z, Comparison between the induced membrane technique and distraction osteogenesis in treating segmental bone defects: An experimental study in a rat model. PloS one. 2019     [PubMed PMID: 31860680]
[8] McCarthy JG,Schreiber J,Karp N,Thorne CH,Grayson BH, Lengthening the human mandible by gradual distraction. Plastic and reconstructive surgery. 1992 Jan;     [PubMed PMID: 1727238]
[9] Fearon JA, Halo distraction of the Le Fort III in syndromic craniosynostosis: a long-term assessment. Plastic and reconstructive surgery. 2005 May;     [PubMed PMID: 15861055]
[10] Winston KR,Ketch LL,Dowlati D, Cranial vault expansion by distraction osteogenesis. Journal of neurosurgery. Pediatrics. 2011 Apr;     [PubMed PMID: 21456905]
[11] Day KM,Gabrick KS,Sargent LA, Applications of Computer Technology in Complex Craniofacial Reconstruction. Plastic and reconstructive surgery. Global open. 2018 Mar     [PubMed PMID: 29707444]
[12] Yen S,Gaal A,Smith KS, Orthodontic and Surgical Principles for Distraction Osteogenesis in Children with Pierre-Robin Sequence. Oral and maxillofacial surgery clinics of North America. 2020 May     [PubMed PMID: 32247440]
[13] Drew SJ,Kapadia H, LeFort Distraction in the Cleft Patient. Oral and maxillofacial surgery clinics of North America. 2020 May     [PubMed PMID: 32151373]
[14]     [PubMed PMID: 25383052]
[15] Knackstedt R,Bassiri Gharb B,Papay F,Rampazzo A, Comparison of Complication Rate Between LeFort III and Monobloc Advancement With or Without Distraction Osteogenesis. The Journal of craniofacial surgery. 2018 Jan     [PubMed PMID: 29194272]
[16] Tahiri Y,Viezel-Mathieu A,Aldekhayel S,Lee J,Gilardino M, The effectiveness of mandibular distraction in improving airway obstruction in the pediatric population. Plastic and reconstructive surgery. 2014 Mar;     [PubMed PMID: 24572880]
[17] Greives MR,Ware BW,Tian AG,Taylor JA,Pollack IF,Losee JE, Complications in Posterior Cranial Vault Distraction. Annals of plastic surgery. 2016 Feb;     [PubMed PMID: 25954848]
[18] Breik O,Tivey D,Umapathysivam K,Anderson P, Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review. International journal of oral and maxillofacial surgery. 2016 Jun;     [PubMed PMID: 26867668]
[19] Al-Namnam NMN,Hariri F,Rahman ZAA, Distraction osteogenesis in the surgical management of syndromic craniosynostosis: a comprehensive review of published papers. The British journal of oral     [PubMed PMID: 29661509]
[20] Leu GR,Scott AR, A Standardized Care Pathway following Mandibular Distraction in Infants Less Than 3 Months of Age. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2019 Nov;     [PubMed PMID: 31331240]