Onlay vascularized fibular grafting as a salvage procedure for the management of nonunion after reconstruction of the femur following tumor resection

Abstract

Purpose:

The femur is prone to nonunion after biologic reconstruction following tumor resection, due to high bending forces. Nonunion at the host–graft junction is difficult to treat since the graft is in an avascular state. We aimed to investigate the clinical and radiographic results of an onlay free vascularized fibular grafting (VFG) as a salvage procedure for nonunion management after biologic reconstruction of the femur following bone tumor resection.

Methods:

We retrospectively reviewed 10 patients (8 men and 2 women, median age: 15.5 years, range: 10–47) who underwent an onlay VFG for nonunion after intercalary reconstruction of the femur using an allograft (n = 7) or pasteurized autograft (n = 3), following tumor resection. The median follow-up period after VFG was 85.7 (24.6–163.5) months.

Results:

The median time to union between the host bone and the VFG osteotomy sites was 3.5 (2.8–4.5) months. The median time to union at the host–graft junctions was 10.6 (6.6–12.7) months. Two postoperative complications requiring revision surgery occurred in two patients: one graft fracture and one deep infection with synchronous graft fracture. Internal fixation was required in the patient with graft fracture. The patient with the infection and synchronous graft fracture was treated using debridement, antibiotics, and an external fixator. The median Musculoskeletal Tumor Society functional score was 88% (60–97%) at the final follow-up.

Conclusion:

Onlay VFG as a salvage procedure for nonunion of a biologic intercalary reconstruction of the femur after tumor resection is a useful treatment option.

Keywords

femur free vascularized fibular graft intercalary reconstruction nonunion

Introduction

The femur is the most common site of occurrence of primary bone tumors.¹ Intercalary resection is performed for malignant bone tumors that develop in the region of the diaphysis or the meta-diaphysis of the femur to preserve the knee joints.^2

–5 Surgical options for reconstructing femoral defects following intercalary resection include massive allografts,^6

–9 pasteurized or irradiated autografts,^10
–12 nonvascularized or vascularized fibular grafts,^13,14 and spacers or an endoprostheses.^15,16

Despite advances with spacers and endoprostheses,^16,17 biological reconstruction using massive allografts following intercalary resection is widely used^7,18 and produces long-term success rates and good functional outcomes in 82–84% of patients.^4,19,20 However, they have high nonunion rates, ranging from 12% to 35%.^18,20
–22 Biological reconstruction using pasteurized autografts is a favored option for ensuring tight contact between the bone ends, low medical cost, and good osteoinductivity.^23,24 They also have high nonunion rates similar to allografts.¹¹

Nonunion at the host–graft junction after biological reconstruction do not follow the typical nonunion healing physiology, since the graft is in an avascular state, making nonunion difficult to treat.^25,26 Although the majority of patients with nonunion achieved a union through additional procedures including autogenous bone grafting, additional plating, or a plate change, nonunion persisted in some patients.²² Vascularized fibular grafting (VFG) has been used to reconstruct segmental bone defects alone or in combination with other types of bone grafts following intercalary resection of long bones and has shown good results.^13,14,27,28 Recently, studies have reported using onlay VFG as a method of treating nonunion and fracture following biological intercalary reconstruction of long bones.^29,30

The femur is more prone to nonunion than other regions of the body after intercalary reconstruction, due to high pressure and compressive and bending forces.^19,31 In this study, we report the radiographic and clinical results of onlay VFG for the treatment of nonunion that developed following biological intercalary reconstruction for malignant bone tumors of the femur.

Materials and methods

We retrospectively reviewed 10 patients who underwent onlay VFG for nonunion that developed postbiological intercalary reconstruction, using massive allografts or pasteurized autografts for malignant bone tumors of the femur, between May 2002 and May 2012. A single surgeon performed all the procedures including the harvesting and transplanting of vascularized fibular grafts. The study was approved by the institutional review board of Kyung Hee University Hospital. Informed consents of all patients were obtained before the review.

Surgical technique and rehabilitation

Angiography was performed on recipient and donor sites before surgery to assess any abnormalities of the peroneal vessels at the donor sites and to identify the appropriate vessels for anastomosis with the peroneal vessels in the femoral regions at the recipient site. The recipient site was prepared prior to fibular harvest. A medial approach was used for the recipient site in all patients. Debridement of necrotic or fibrotic tissue at the nonunion site was performed. Autogenous cancellous bone graft harvested from the ilium was packed around the sites of nonunion. Fibulas were harvested from the contralateral side. The proximal and distal periosteum on the lateral side of fibula was elevated. The harvested fibula was at least 2 cm longer than the length of the femoral defect to allow a minimum overlapping of 1 cm for each osteotomy. The harvested fibulas were placed to overlap host–graft junctions, where nonunion occurred, and parallel and medial to the femur. They were then fixed to the femur with two lag screws or K-wires. Periosteum of the fibula was sutured both proximally and distally across the host–graft junctions. All anastomoses were performed between one artery and two veins. At the recipient site, the collateral branch of the superficial femoral artery or the collateral branch of the profunda femoral artery were used.

In general, stitches were removed and the patients were discharged 2 weeks after surgery. The patients were followed up every 2–3 months after discharge until a union was observed, and once every year after union was achieved. Isometric exercise for the flexors and extensors started as soon as possible after surgery. Weight-bearing leg exercises using crutches started 3 months after surgery. Patients were permitted to perform full weight-bearing exercises starting from a median 12.5 (range: 8–14) months after surgery. Bone scintigraphs using Technetium-99 methylene diphosphonate were used to assess blood flow into the transplanted vascularized fibular grafts.

Radiographic evaluation

The clinical scores and radiographic findings were collected from detailed retrospective reviews of charts, containing previously recorded findings that were performed by a surgeon specializing in reconstructions. Radiographs were obtained to confirm evidence of union or complications such as fractures. Unions between the host bone and the osteotomy site of transplanted fibula and between the host bone and the allograft or pasteurized autograft were assessed using radiography. Union was defined that bridging callus formation observed between the host bone and the osteotomy site of transplanted fibula, and that no longer visible radiolucent line or bridging calluses formation of three cortices observed between the host bone and the allograft or pasteurized autograft on radiography.

Clinical evaluation

A clinical assessment was conducted based on the Musculoskeletal Tumor Society (MSTS) score.³² The MSTS rating scale assesses physical function using the following six items: pain and function, emotional acceptance, support, walking ability, and gait. Each item is rated on a 5-point scale, with a total score of 30 points (100%). The MSTS score classifies the degree of physical function as follows: excellent (80–100%), good (70–79%), moderate (60–69%), fair (50–59%), and poor (<50%).

Results

The patients comprised eight men and two women, with a median age of 15.5 (range: 10–47) years at the time of the surgery. Malignant bone tumors of the femur included osteosarcoma (n = 6), malignant fibrous histiocytoma (n = 2), Ewing’s sarcoma (n = 1), and malignant myoepithelioma (n = 1). Nine patients received chemotherapy before and after tumor resection, and no patient underwent radiotherapy. The median time from biological reconstruction to VFG was 28.6 (range: 11.7–123.8) months, and the median follow-up period from VFG was 85.7 (range: 24.6–163.5) months. All patients were monitored until they developed a bone union. Grafts used in the initial reconstruction following intercalary resection included allografts (n = 7) and pasteurized autografts (n = 3). Regarding the site of nonunion, a nonunion developed at proximal host–graft junctions in seven patients (six with bone allografts and one with pasteurized autografts), at distal host–graft junctions in one patient with pasteurized autografts, and at both proximal and distal host–graft junctions in two patients (one with bone allografts and one with pasteurized autografts; Table 1).

Table 1.

Patient characteristics.

No.	Age	Sex	Diagnosis	Graft	Nonunion site	Interval to VFG (month)	Length of VFG (cm)	CTx	No. of additional surgeries prior to VFG	Follow-up (month)
1	10	F	OS	Allograft	Proximal	28.9	23	Pre/post	2	24.6
2	10	M	OS	Allograft	Proximal	11.7	18	Pre/post	2	94.4
3	17	M	OS	Allograft	Proximal	24.8	13	Pre/post	1	49.2
4	11	M	OS	Pasteurized	Both	24.8	20	Pre/post	2	114.1
5	14	M	OS	Allograft	Both	28.0	29	Pre/post	4	158.0
6	38	F	OS	Allograft	Proximal	28.3	24	Pre/post	3	65.7
7	13	M	ES	Pasteurized	Distal	36.0	21	Pre/post	2	159.8
8	21	M	Malig. MEM	Allograft	Proximal	40.3	13	None	2	51.5
9	44	M	Malig. FHC	Pasteurized	Proximal	96.6	26	Pre/post	3	163.5
10	47	M	Malig. FHC	Allograft	Proximal	123.7	20	Pre/post	3	77.0

OS: osteosarcoma; ES: Ewing’s sarcoma; Malig.: malignant; MEM: myoepithelioma; FHC: fibrous histiocytoma; VFG: vascularized fibular grafting; CTx: chemotherapy

Radiographic outcomes

Unions between the host bone and the osteotomy site of transplanted fibula and between the host bone and the allograft or pasteurized autograft were observed in all patients at the final follow-up. The median time to union between the host bones and the osteotomy sites of the transplanted fibulas was 3.5 (range: 2.8– 4.5) months. The median time to union at host–graft junctions was 10.6 (range: 6.6– 12.7) months (Figure 1; Table 2). No evidence of acute VFG failure was found on bone scintigraphs obtained within 2 months postsurgery.

Figure 1.

(a) Pre-VFG radiograph reveals nonunion at both proximal and distal host–graft bone junctions. (b) Immediate post-VFG radiograph reveals medially located harvested fibula. (c) Radiograph at 4 months postsurgery reveals a union between the host bone and the fibula osteotomy site. (d) Radiograph at 10 months postsurgery reveals a union at the host–graft junction. VFG: vascularized fibular grafting.

Table 2.

Radiographic and clinical outcomes.

No.	Time to union (months)		Complication	Additional surgery	Metastasis	Oncologic outcome	MSTS (%)
No.	Host–fibula	Host–graft	Complication	Additional surgery	Metastasis	Oncologic outcome	MSTS (%)
1	3.0	11.3				CDF	86.7
2	3.2	9.1			MET	DOD	60.0
3	3.8	10.1				CDF	93.3
4	2.9	6.6	LLD	Lengthening		CDF	90.0
5	2.8	9.4	Fracture	OR/IF		CDF	73.3
6	4.0	11.3	Knee stiffness	Manipulation		CDF	66.7
7	2.9	12.7				CDF	96.7
8	4.1	10.4				CDF	93.3
9	4.2	12.1	Fracture, infection	OR/IF, I&D, External fixation		CDF	80.0
10	4.5	10.7				CDF	90.0

LLD: leg length discrepancy; MET: metastases; CDF: continuously disease free; DOD: died of disease; MSTS: musculoskeletal tumor society score; OR/IF: open reduction and internal fixation; I&D: irrigation and debridement.

Clinical outcomes

One patient died of lung metastasis at 94.4 months after VFG. The remaining nine patients were continuously disease-free until the final follow-up. No local relapse was observed in any patient. The physical function assessment results indicated that seven patients scored within the excellent range, one scored within the good range, and two scored within the moderate range. The two patients who scored within the moderate range included one patient who had lung metastasis (MSTS, 60%), and one patient who had undergone manipulation under anesthesia for a stiff knee (MSTS, 66.7%). The median MSTS score at the final follow-up was 88.4% (range: 60.0–96.6%). The median MSTS score for each item was 84% for pain (60–100%), 90% for walking (66–100%), 86% for gait (60–100%), and 96% for support (80–100%).

Complications

There were no donor site complications. A stiff knee at the recipient site was observed in one patient, and the knee was subsequently manipulated under anesthesia. Major complications requiring revision surgery at the recipient site were observed in two patients: one case of graft fracture (bone allograft) and one case of graft fracture accompanied with deep infection (pasteurized autograft). The allograft fracture occurred at the proximal region of the distal host–graft junction due to trauma, at 32 months after VFG, when a union was achieved. The fracture was treated via plate osteosynthesis and morcellized autobone grafts, collected from the anterior superior iliac spine. The fracture of the pasteurized autograft occurred at the mid-shaft of the graft due to a fall occurring at over 86.6 months after VFG when a union was achieved. This patient had been treated with antibiotics and debridement 17 months prior, due to a deep infection at the fracture site. We confirmed that the patient had a fracture with deep infection, and treatment comprised of debridement, external fixation devices, and administering antibiotics. After the infection was controlled, a conversion of external fixation to internal fixation was performed using a plate.

Discussion

An important finding of this study is that onlay VFG produces satisfactory radiographic and clinical results as a salvage procedure for nonunion that develops after biological intercalary reconstruction of the femur. Vander Griend²² reported nonunion in 20 of 120 patients (16.6%) who underwent massive allograft reconstruction. Patients with nonunion underwent additional procedures including bone grafting, additional plating, and a plate change for the bone union, with more than one procedure for each type. Despite these patients undergoing additional procedures, one patient required an amputation and two continued to have a nonunion; only 17 patients achieved a union. In these patients with nonunion, onlay VFG could be an alternative treatment option as a salvage procedure.

VFG can be performed in conjunction with or in addition to biological reconstruction. VFG in combination with massive allograft reconstruction has the advantage of achieving a fast union, owing to the osteogenic potential of vascularized fibulae, and compensating for bone weakening, due to bone resorption through the bone allograft via the allograft’s mechanical support and progressive hypertrophy of the fibula.³³ Chang and Weber¹³ reported union achievement in five of six patients who underwent onlay VFG for nonunion at host–graft junctions. In addition, Campanacci et al.²⁹ attempted to salvage failed intercalary reconstruction of the femur in 12 patients (7 with allografts, 4 with cement spacers, and 1 with a prosthesis) through performing onlay VFG in which bone allografts were preserved for 7 patients with bone allografts, as was also accomplished in this study, and through performing VFG for the remaining 5 patients after the removal of spacers and prostheses. They reported unions in 10 patients. The present study is similar to the seven cases in Campanacci’s study that involve nonunion of the femur. Although complications requiring revision surgery were observed in two patients in our study, union was achieved in all patients whose existing bone grafts were preserved. This study also showed satisfactory clinical outcomes.

Complication rates of onlay VFG range from 25% to 64% and are relatively high.^13,27,29,30 Major complications at the recipient site that require revision surgery include fracture of the bone graft, with the most common complication being continued nonunion and femoral artery thrombosis following vascular anastomosis. Minor complications include a stiff knee.^13,27

–30 Donor site morbidity must be taken into account depending on the site of vascularized fibula collection during VFG. Donor site morbidities include flexor hallucis longus contracture, transient peroneal nerve palsy, and wound complications.^30,34 No donor site morbidity was observed in this study. The rate of recipient site morbidity was 30% and consisted of major complications (20%) and minor complications (10%). The rates of complications found in this study were similar to those reported in other studies.

The present study has several limitations. First, it is a retrospective study. It is necessary to conduct prospective research assessing the advantages of onlay VFG for the treatment of a nonunion that develops after biological intercalary resection. Another limitation involved the small cohort size and the absence of a control group. However, a small cohort size has also been a limitation of previous studies.^13,29,34 This is because only a limited number of VFG procedures for nonunion can be performed at a single hospital. Future research should include a large multicenter cohort and comparative studies involving a larger population of patients. As a final limitation, we did not obtain MSTS scores prior to the VFG procedure. Therefore, we could not conclude whether the presented MSTS scores represented an improvement or not compared to the scores prior to the VFG procedure.

Conclusion

Onlay VFG as a salvage procedure for nonunion of a biologic intercalary reconstruction after tumor resection of the femur is a useful treatment option. However, it must be noted that onlay VFG has high rates of complications.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Jae Hoon Lee

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