Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion: Problems solved and unsolved

Table 1 Number of five-year literature sources found and studied

	Total number of sources found / articles on bone defects	Number of selected sources, including congenital conditions	Number of articles per year / number of reviews / basic research articles	Number of full text articles included in this review
Distraction osteogenesis techniques
PubMed	155/116	108	2015: 18/1/1	50
Scopus	169/136		2016: 33/2/0
Web of Science	144/105		2017: 23 /2/0
			2018: 17/1/2
			2019: 17/1/0
Induced membrane technique
PubMed, Scopus, Web of Science	121/104	87	2015: 8/2/2	10
			2016: 16/5/4
			2017: 24 /7/4
			2018: 17/2/10
			2019: 22/2/4
Free vascularized fibular graft
PubMed, Scopus, Web of Science	138/52	37	2015: 5/0/0	5
			2016: 7/2/0
			2017: 11/2/0
			2018: 8/0/0
			2019: 6/1/0

Table 2 Summary of merits and problems of the methods used for nonunion and bone defect management

Merits	Shortcomings	Problems or adverse events that are considered failures or may cause it
Ilizarov non-free bone plasty
(1) High-quality, biologically normal new bone tissue of massive proportions is generated through distraction osteogenesis; (2) The regenerated bone has good vascularity; (3) The limb is well stabilized with the circular fixator leading to union at the same time; (4) Coexistent bone issues such as deformity correction, equalization of leg length can be addressed simultaneously and effectively; (5) There is no risk of rejection or necrosis of the non-free graft; (6) Soft tissue healing, free tissue transfer after frame placement is possible; (7) The risk of deep infection is low; (8) The method is suitable for both infected and non-infected cases; (9) It is practical in financially constrained cohorts of patients in medical centers; (10) Full weight-bearing is early after the operation; (11) There are no problems of the donor site; and (12) Stimulation with osteoprogenitor cells is possible	(1) Implementation needs trained professionals; (2) The complexity of the Ilizarov apparatus placement necessities its re-arrangements during treatment; (3) Scarring associated with the wires and half-pins as they progress down occurs; (4) Pin-tract infection is frequent; (5) Wearing time of the circular frame is long; (6) Breakage of wires and pins that may results in frame instability; (7) Patients have physical stress due to pain, inconvenience of sleeping and doing hygiene, negative impact on the patients' mental health; (8) There is some risk of joint contractures and the necessity of doing exercise therapy constantly; (9) It is difficult to mount the apparatus in the areas with a large soft-tissue envelope such as the thigh; (10) The method implies frequent postoperative manipulations (change of dressings, radiographic monitoring of bone formation); (11) Bone grafting at the docking site is mostly required; and (12) The cost of the circular fixator ranges a lot and depends upon the country	(1) Frequent pin-tract infection may lead to wire-tract osteomyelitis; (2) Fractures of the regenerate upon frame removal in massive defects are possible; (3) Deformity of the regenerated bone within 3-4 mo upon frame removal may develop; (4) Osteogenesis failure or incomplete osteogenesis due to technical mistakes or low bone regeneration potential may occur; and (5) Failure of union at the docking site may happen
Induced membrane technique
(1) Extensive segmental defects may be bridged; (2) The induced membrane favours osteogenesis as it is vascularized, bioactive and protects the graft from resorption; (3) Suitable for both infected and non-infected cases; (4) Antibiotics may be impregnated locally into the spacer; (5) Stimulation with osteoprogenitor cells during the second stage is possible; and (6) Weight-bearing is possible as bone fragments are stabilized with external or internal fixators	(1) Long period of treatment and several stages of the surgical procedures are necessary; (2) A considerable amount of autogenous graft is needed to fill the bone defect; (3) The average time to bone union is rather long; (4) Intraosseous blood supply is not adequate; (5) Incomplete remodeling of massive grafts is frequent; (6) Leg length discrepancies in large defects cannot be corrected completely due to restricted graft material; (7) Possibility to address gross deformity and leg length discrepancy is limited; and (8) Gross scarring is inevitable	(1) Necrosis and rejection of grafts, especially when allograft is added for graft volume; (2) Pathological fractures in the defect area may happen; (3) An Internal fixator may break or become instable; (4) Re-grafting due to failure of primary graft healing occurs; and (5) Coexistent bone issues such as gross deformity and leg length discrepancy need to be addressed separately following treatment
Free vascularized fibular graft
(1) Defect may be covered with one procedure; (2) Bone union is achieved within the regular terms for fracture treatment; (3) Primary postresection defect grafting due to tumors is effective; and (4) Weight-bearing is possible as bone fragments are stabilized with external or internal fixators	(1) Surgical intervention is executed with two operative procedures and is rather time-consuming; (2) It requires special training as microsurgery is used; (3) It is rather expensive as needs special medication and equipment; (4) Material for grafting is limited; (5) There are problems of donor site, such as pain and ankle joint problems; (6) Extensive scars are inevitable; (7) Graft remodeling may be incomplete due to hemocirculation disorders in a large graft; (8) Limb bracing is required until adequate hypertrophy of the graft; (9) Valgus deformity may develop at the donor site after harvesting the fibula; (10) The procedure is problematic after previous surgeries and if soft tissues are damaged by scars; (11) Gross scarring is inevitable; and (12) Possibility to address gross deformity and leg length discrepancy is limited	(1) Gross vascular problems (thrombosis) may develop and may lead to necrosis, graft rejection and infection; (2) Pathological fractures of massive grafts may develop; (3) Internal fixator break or instability may occur; (4) Failure of grafting due to nonunion is possible; and (5) Coexistent bone issues such as gross deformity correction and equalization of leg length need to be addressed separately following treatment

Table 3 Web of Science + Scopus search results for the period 2015-2019 (key words: Ilizarov method, bone defects)

Web of Science + Scopus search
Number of sources found	169	100%
Infected defects	73	43.2%
Post-traumatic defects	59	34.9%
Acute trauma	13	7.7%
Bone tumors	8	4.7%
Congenital diseases	7	4.1%
Other	6	3.6%
Animal model, basic research	3	1.8%

Table 4 Largest clinical studies published in 2015-2019 and their outcomes with distraction osteogenesis techniques

Ref.	Number of patients	Fixation type / bone union rate	Problems requiring reoperations after frame removal or failures
Defects of tibia
Kinik et al[14], 2019, Turkey	30	Ilizarov/96.66%	1 nonunion, 1 refracture of the regenerate, 1 late deformity of the regenerate
Fahad et al[15], 2019, Pakistan	51	Ilizarov/96%	2 nonunions (1 amputation due to sepsis), 2 reinfections eradicated during main treatment
Thakeb et al[16], 2019, Egypt	50	Ilizarov/100%
Catagni et al[17], 2019, Italy	86	Ilizarov/100%	4 refractures
Wu et al[18], 2018, China	40	Ilizarov/100%
Yilihamu et al[19], 2017, China	129	Ilizarov + Orthofix/100%
McNally et al[20], 2017, United Kingdom	79	Ilizarov/86.1%	2 refractures, recurrence of infection, 6 after-frame reoperations
El-Alfy et al[21], 2017, Egypt	28	Ilizarov/100%
Meleppuram et al[22], 2016, India	42	Ilizarov/100%
Abuomira et al[23], 2016, Italy	55	Ilizarov + Taylor spatial frame/89%	1 osteitis, 2 bending of regenerate, 2 refractures of the docking site, 1 nonunion
Rohilla et al[24], 2016, India	70	Ilizarov vs rail fixator/77% vs 80% of primary union	The rail fixator was converted to a ring fixator in two patients, 2 after-frame refractures
Sadek et al[25], 2016, Egypt	30	Ilizarov vs two stage internal osteosynthesis	1 nonunion in internal group
Bernstein et al[26], 2015, United States	30	Ilizarov/77%	-
Peng et al[27], 2015, China	58	Ilizarov/100%	4 equinovarus deformities, 1 infection recurrence at the docking site
Defects due to acute fractures
van Niekerk et al[28], 2017, South Africa	24	Ilizarov/91.7%	2 amputations, 1 persistent deep infection in a HIV-positive patient, mangled extremity
Salih et al[29], 2018, United Kingdom	31	Ilizarov/96%	4 after-frame refractures, 2 regenerate deformities after frame, 1 stiff non-union
Fuermitz et al[30], 2016, Germany	25	Ilizarov or hybrid/92%	2 amputations due to comorbidities
Azzam et al[31], 2016, Еgypt	30	Ilizarov/93.3%	1 post-frame fracture
Thakeb et al[32], 2016, Egypt	161	Ilizarov	1 failure
Ajmera et al[33], 2015, India	30	Monolateral/93%	2 nonunions
Large-scale defects requiring tibilization of the fibula
Meselhy et al[34], 2018, Egypt	141	Ilizarov/100%
Zaman et al[35], 2017, Pakistan	121	Ilizarov/100%	1 supracondylar femoral fracture while removing frame
Defect of femur
Bakhsh et al[36], 2019, Pakistan	50	Ilizarov/98%	2 nonunions, 1 refracture
Zhang et al[37], 2017, China	41	Monolateral/98%	1 refracture, 5 cases of docking site nonunion
Mudiganty et al[38], 2017, India	22	Monolateral rail/97.5%
Agrawal et al[39], 2016, India	30	Monorail/100%	5 delayed union with autograft
Defects of femur and tibia
Ariyawatkul et al[40], 2019, Thailand	171	Ilizarov/94%	1 nonunion
Lowenberg et al[41], 2015, United States	127	Ilizatov/96%	3 amputations due to comorbidities
Yin et al[42], 2015, China	110	Ilizarov for tibia, monolateral for femur/100%	2 after-frame refractures
Tumor- resection defects
Eralp et al[43], 2016 (Turkey, United States, Egypt)	20	Various types of external fixators/100%	1 knee arthrodesis
Wang et al[44], 2019, China	101	Monolateral/90%	1 amputation at long-term due to cancer relapse

¹Smaller groups for rare conditions treated with the Ilizarov method (severely comminuted fractures, pan tibial defects, large periarticular defects). HIV: Human immunodeficiency virus.

Table 5 Comparative studies of the methods in the period 2015-2019

Ref.	Number of patients	Method, segments, fixator	Complications and problems requiring operations after frame removal or failures	Recommendations to solve the problems (conclusions)
Wen et al[3], 2019, China	317	IMT (106), DO (132), FVFG (79), post-traumatic long bones, monolateal, ring fixators, nails, plates	Major complications: (1) IMT: Hardware failure (3 cases), joint ankylosis or fusion (6 cases), > 3 cm LLD (5 cases), clubfoot or dropping foot (3 cases), and residual deformity requiring secondary procedures (4 cases); (2) DO: Deep infection (1 case), joint ankylosis or fusion (8 cases), > 3 cm LLD (3 cases), clubfoot or dropping foot (6 cases), and residual deformity requiring secondary procedures (2 cases); (3) FVFG: Hardware failure and/or refracture (7 cases), nonunion (5 cases), joint ankylosis or fusion (6 cases), > 3 cm LLD (3 cases), and residual deformity requiring secondary procedures (3 cases); and (4) Complication rates were 22.6%, 25.8%, and 26.6% (P > 0.05), respectively	The methods compared resulted in equivalent long-term outcomes. Overall complication rates were analogous among the three methods. A circular external fixator and intramedullary nail provide better stability than a monolateral external fixator and locking plates, which may benefit early partial weight bearing, thus stimulating consolidation. An approach worth exploring is to cross over from external to internal fixation in step 2 in patients treated with IMT. Special attention should be paid to alignment, external fixator stability, and care of all foot and ankle joints
Tong et al[75], 2017, China	39	IMT (20), IBT (19), posttraumatic osteomyelitis, tibia, femur	The bone outcomes were similar between groups [excellent (5 vs 7), good (10 vs 9), fair (4 vs 2) and poor (1 vs 1)]. IMT group showed better functional outcomes than IBT group	Both IBT and IMT lead to satisfactory bone results following posttraumatic osteomyelitis. IMT had better functional results, especially in femoral cases. IBT should be preferred in cases of limb deformity. IMT may be a better choice in cases of periarticular bone defects
Abdelkhalek et al[82], 2016, Egypt	24	IBT (13), FG (free grafting, 11), tibial defects	1 refracture at the regenerate site in IBM group after removal of the external fixator, 1 stress fracture in FG group. Rates of poor results: 7.6%, 9.1% respectively	Segmental tibial defects can be effectively treated with both methods. The FG method provides satisfactory results and early removal of the external fixator, but its limitation is severe infection and LLD. Also, it requires a long duration of limb bracing until adequate hypertrophy of the graft. IBT has the advantages of early weight bearing, treatment of postinfection bone defect and LLD in a one-stage surgery but a long external fixation time
Borzunov et al[78], 2019, Russia	13	IMT + DO (6) vs DO (7), congenital pseudarthrosis of the tibia	1 nonunion in IMT + DO but no refractures within a year, 29% after-frame refractures in DO group	The combined use of non-free Ilizarov bone grafting according to Ilizarov and Masquelet technology achieves bone fusion of congenital pseudoarthrosis and disease-free course of the condition within a year follow-up

LLD: Leg length discrepancy; IMT: Induced membrane technique; DO: Distraction osteogenesis; IBT: Ilizarov bone transport; FVFG: Free vascularized fibular graft; FG: Fibular graft.