Clinical and functional outcomes of tibial intercalary allografts after tumor resection

Reconstruction after intercalary resection of the tibia is demanding due to subcutaneous location, poor vascularity of the tibia, and high infection rate. The purpose of this study was to evaluate the survivorship, complications, and functional outcome of intercalary tibial allograft reconstructions following tumor resections. Intercalary tibia segmental allografts were implanted in 26 consecutive patients after segmental resections. Patients were followed for an average of 6 years. Allograft survival was determined with the Kaplan-Meier method. Patient function was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system. Survivorship was 84% (95% confidence interval [CI], 98%-70%) at 5 years and 79% (95% CI, 63%-95%) at 10 years. Allografts were removed in 5 patients due to 3 infections and 2 local recurrences. Two patients showed diaphyseal nonunion, and 3 patients underwent an incomplete fracture; no allografts were removed in these patients. Average MSTS functional score was 29 points (range, 27-30 points). Despite the incidence of complications, this analysis showed an acceptable survivor-ship with excellent functional scores. The use of intercalary allograft has a place in the reconstruction of a segmental defect created by the resection of a tumor in the diaphyseal or metaphyseal portion of the tibia.     

Intramedullary, antibiotic-loaded cemented, massive allografts for skeletal reconstruction 26 cases compared with 19 uncemented allografts

We compared the outcomes of 26 intramedullary cemented massive allografts with 19 allografts without cementation; all allografts were used for reconstruction after excision of bone sarcomas. In the cementation group, 12 allografts were used as osteochondral grafts (proximal humerus 4, proximal tibia 4, and distal femur 4), 7 as intercalary diaphyseal allografts of the femur, and 7 for a knee arthrodesis. In the uncemented allografts, 3 allografts were used as osteochondral grafts (proximal humerus 2, proximal tibia 1), 2 as intercalary diaphyseal allograft of the femur, and 14 for a knee arthrodesis. The average length of follow-up was 40 (25-60) months. 14 of 26 cemented allografts had an excellent (osteotomy line: not visible) or good (fusion 75% of the cortical thickness) healing of the junction site. Infection developed in 1 allograft. Fracture occurred in 4 of 12 cemented osteochondral allografts due to a subchondral collapse (all in the proximal tibia). Fractures at the junction site in the lower extremity developed in 4 of 22 cemented allografts. In 19 allografts without cementation, 11 had excellent or good healing of the junction. Late infection developed in 4 allografts, fracture of the allograft in 3 cases, and junction fracture in 3 of 17 patients with reconstruction of the lower extremity. Intramedullary graft cementation seems to reduce the fracture and infection rates.     

Experimental model for allograft incorporation and allograft fracture repair.

This study describes a rat model of allograft osteotomy healing. An intercalary skeletal defect was created in adult Lewis rats by resecting a 2-cm segment of the femur in the diaphysis, including the periosteum and the cuff of muscle layers. The skeletal defects were replaced with fresh-frozen devascularized intercalary allografts from Sprague-Dawley rats. A transverse osteotomy was made in the middle of the allograft. The osteotomized segments were stabilized with an intramedullary threaded Kirschner wire, which allowed immediate ambulation. Radiographic and histological examination at 4 and 8 weeks revealed a characteristic healing process at three different interfaces. Radiographically, the distal metaphyseal host-donor junction healed faster than the proximal diaphyseal host-donor interface. The osteotomy site did not have evidence of an intramembranous or endochondral repair process. This model can serve as a baseline for assessing allograft incorporation and fracture repair.     

Estimation of defect volume in segmental defects of the tibia and femur

BACKGROUND: With the advent of modern limb salvage techniques, segmental bone loss in the lower extremity has become more common. METHODS: To aid preoperative planning when dealing with segmental bone loss in the femur and tibia, we performed a cadaveric study to estimate the volume of autogenous or allograft material required to fill defects located in various areas of the bones. RESULTS: The greatest volume was generally required in metaphyseal defects, with an average of 12 cc/cm in the distal femur and proximal tibia, 11 cc/cm in the proximal femur, and 6 cc/cm in the distal tibia. Diaphyseal defects were found to have the least variability with regard to the volume of graft material required for different specimens. Femoral diaphyseal defects required 7 cc/cm and tibial diaphyseal defects required 5 cc/cm. A slightly larger volume of allograft material was needed to fill all defects compared with autograft. CONCLUSION: This method allows one to estimate the amount of graft required for a defect of the femur and the tibia.     

Overlapping allograft in reconstructive surgery for malignant bone tumours in paediatric patients: a preliminary report

The use of allografts for the treatment of bone tumours in children is limited by nonunion and the difficulty of finding a suitable graft. Furthermore, appositional growth can't be expected of an allograft. We used an overlapping allograft in 11 children, with a mean age of ten years (4 to 15), with a mean follow-up of 24.1 months (20 to 33). There were five intercalary and six intra-articular resections, and the tumours were in the femur in six cases and the humerus in five. Rates of union, times to union, remodelling patterns and allograft-associated complications were evaluated. No allograft was removed due to a complication. Of the 16 junctional sites, 15 (94%) showed union at a mean of 3.1 months (2 to 5). Remodelling between host and allograft was seen at 14 junctions at a mean of five months (4 to 7). The mean Musculoskeletal Tumor Society score was 26.5 of 30 (88.3%). One case of nonunion and another with screw protrusion required re-operation. Overlapping allografts have the potential to shorten time to union, decrease rates of nonunion and have positive appositional growth effect.     

Segmental femur reconstruction using an intercalary allograft with an intramedullary vascularized fibula bone flap

The use of intercalary allografts has been an important innovation for use in limb-salvage surgery. However, the principal disadvantage of intercalary allografts is a high incidence of nonunion, fracture, and infection. With a recent trend toward higher doses of chemotherapy, an increased incidence of nonunion and healing problems can be anticipated with the use of allografts. In this article, the authors report two cases in which a vascularized fibula bone flap was used with an intercalary allograft, utilising an intramedullary approach, for immediate femur reconstruction following sarcoma resection. The rationale for this approach is to combine the mechanical strength of an allograft with the biologic activity of a vascularized bone flap. The allograft provides bone stock and early stability, while the addition of the vascularized bone flap substantially facilitates the host-allograft union.     

Reconstruction after intercalary resection of malignant bone tumours: comparison between segmental allograft and extracorporeally-irradiated autograft

We reviewed 29 patients who had undergone intercalary resection for malignant tumours. Of these, 14 had received segmental allograft reconstruction and 15 extracorporeally-irradiated autograft. At a mean follow-up of 71 months (24 to 132), 20 were free from disease, five had died and four were alive with pulmonary metastases. Two patients, one with an allograft and one with an irradiated autograft, had a local recurrence. Reconstruction with extracorporeally-irradiated autograft has a significantly lower rate of nonunion (7% vs 43%, p = 0.031) but an insignificantly higher rate of fracture (20% vs 14%, p = 0.535) than that with segmental allograft. Using the Enneking functional evaluation system, the mean postoperative score for the patients without local recurrence was 87% (80% to 96%) and was similar in both groups. Extracorporeally-irradiated autograft could be an acceptable alternative for reconstruction after intercalary resection, especially in countries where it is difficult to obtain allografts.     

Allografts about the Knee in Young Patients with High-Grade Sarcoma

Reconstruction after resections for high-grade sarcomas about the knee in children and adolescents is a challenging problem because of the large soft tissue and skeletal defects, the effects of adjuvant therapy, and the potential for long-term use of the limb. One hundred sixteen patients, all 18 years or younger, with osteosarcoma or Ewing's sarcoma located between the middle femur and middle tibia, were treated with chemotherapy, resection, and allograft reconstruction. One hundred three patients with osteosarcoma and 13 patients with Ewing's sarcoma had 105 Stage II and 11 Stage III tumors. There were 72 osteoarticular grafts (39 femur, 33 tibia), 28 intercalary grafts (19 femur), seven allograft-prosthetic composites (all femur,) and nine allograft-arthrodeses (seven femur, two tibia). At latest followup, 49% of all of the allograft reconstructions were rated good or excellent, 14% were rated as fair, and 37% were failures. Sixteen percent had an infection develop. Twenty-seven percent of patients had a fracture, 34% had a nonunion, and 14 patients eventually required amputation. Reconstruction of large bone defects about the knee in young patients who are being treated with chemotherapy is difficult. Although complications significantly affect outcome, allografts are a viable option for reconstruction in children with high-grade sarcomas about the knee.     

Intercalary reconstruction following resection of diaphyseal bone tumors: A systematic review

IntroductionThe options for the reconstruction of diaphyseal defects following the resection of bone tumors include biological or prosthetic implants. The purpose of our study was to evaluate different types of intercalary reconstruction techniques, including massive bone allograft, extracorporeal devitalized autograft, vascularized free fibula, and modular prosthesis.MethodsWe performed a systematic review of articles using the terms diaphyseal bone tumor and intercalary reconstruction. All the studies reporting the non-oncological complications such as infection, nonunion and fracture of the intercalary reconstructions were included. We excluded articles published before 2000 or did not involve humans in the study. Case reports, reviews, technique notes and opinion articles were also excluded based on the abstracts. Thirty-three articles included in this review were then studied to evaluate failure rates, complications and functional outcome of different surgical intercalary reconstruction techniques.ResultsNonunion rates of allograft ranged 6%–43%, while aseptic loosening rates of modular prosthesis ranged 0%–33%. Nonunion rates of allograft alone and allograft with a vascularized fibula graft ranged 6%–43% and 0%–33%, respectively. Fracture rates of allograft alone and allograft with a vascularized fibula graft ranged 7%–45% and 0%–44%, respectively. Infection rates of allograft alone and allograft with a vascularized fibula graft ranged 0%–28% and 0%–17%, respectively. All of the allograft (range: 67%–92%), extracorporeal devitalized autograft including irradiation (87%), autoclaving (70%), pasteurization (88%), low-heat (90%) or freezing with liquid nitrogen (90%), and modular prosthesis (range: 77%–93%) had similar Musculoskeletal Tumor Society functional scores. Addition of a vascularized fibula graft to allograft did not affect functional outcome [allograft with a vascularized fibula graft (range: 86%–94%) vs. allograft alone (range: 67%–92%)].ConclusionAseptic loosening rates of modular prosthesis seem to be less than nonunion rates of allograft. Adding a vascularized fibula graft to allograft seems to increase bone union rate and reduce the risk of fractures and infections, though a vascularized fibula graft needs longer surgical time and has the disadvantage of donor site morbidity. These various intercalary reconstruction techniques with or without a vascularized fibula autograft had similar functional outcome.     

Does the Addition of a Vascularized Fibula Improve the Results of a Massive Bone Allograft Alone for Intercalary Femur Reconstruction of Malignant Bone Tumors in Children?

BackgroundMassive bone allograft with or without a vascularized fibula is a potentially useful approach for femoral intercalary reconstruction after resection of bone sarcomas in children. However, inadequate data exist regarding whether it is preferable to use a massive bone allograft alone or a massive bone allograft combined with a vascularized free fibula for intercalary reconstructions of the femur after intercalary femur resections in children. Because the addition of a vascularized fibula adds to the time and complexity of the procedure, understanding more about whether it reduces complications and improves the function of patients who undergo these resections and reconstructions would be valuable for patients and treating physicians.Questions/purposesIn an analysis of children with bone sarcomas of the femur who underwent an intercalary resection and reconstruction with massive bone allograft with or without a vascularized free fibula, we asked: (1) What was the difference in the surgical time of these two different surgical techniques? (2) What are the complications and number of reoperations associated with each procedure? (3) What were the Musculoskeletal Tumor Society scores after these reconstructions? (4) What was the survival rate of these two different reconstructions?MethodsBetween 1994 and 2016, we treated 285 patients younger than 16 years with a diagnosis of osteosarcoma or Ewing sarcoma of the femur. In all, 179 underwent resection and reconstruction of the distal femur and 36 patients underwent resection and reconstruction of the proximal femur. Additionally, in 70 patients with diaphyseal tumors, we performed total femur reconstruction in four patients, amputation in five, and a rotationplasty in one. The remaining 60 patients with diaphyseal tumors underwent intercalary resection and reconstruction with massive bone allograft with or without vascularized free fibula. The decision to use a massive bone allograft with or without a vascularized free fibula was probably influenced by tumor size, with the indication to use the vascularized free fibula in longer reconstructions. Twenty-seven patients underwent a femur reconstruction with massive bone allograft and vascularized free fibula, and 33 patients received massive bone allograft alone. In the group with massive bone allograft and vascularized fibula, two patients were excluded because they did not have the minimum data for the analysis. In the group with massive bone allograft alone, 12 patients were excluded: one patient was lost to follow-up before 2 years, five patients died before 2 years of follow-up, and six patients did not have the minimum data for the analysis. We analyzed the remaining 46 children with sarcoma of the femur treated with intercalary resection and biological reconstruction. Twenty-five patients underwent femur reconstruction with a massive bone allograft and vascularized free fibula, and 21 patients had reconstruction with a massive bone allograft alone. In the group of children treated with massive bone allograft and vascularized free fibula, there were 17 boys and eight girls, with a mean ± SD age of 11 ± 3 years. The diagnosis was osteosarcoma in 14 patients and Ewing sarcoma in 11. The mean length of resection was 18 ± 5 cm. The mean follow-up was 117 ± 61 months. In the group of children treated with massive bone allograft alone, there were 13 boys and eight girls, with a mean ± SD age of 12 ± 2 years. The diagnosis was osteosarcoma in 17 patients and Ewing sarcoma in four. The mean length of resection was 15 ± 4 cm. The mean follow-up was 130 ± 56 months. Some patients finished clinical and radiological checks as the follow-up exceeded 10 years. In the group with massive bone allograft and vascularized free fibula, four patients had a follow-up of 10, 12, 13, and 18 years, respectively, while in the group with massive bone allograft alone, five patients had a follow-up of 10 years, one patient had a follow-up of 11 years, and another had 13 years of follow-up. In general, there were no important differences between the groups in terms of age (mean difference 0.88 [95% CI -0.6 to 2.3]; p = 0.26), gender (p = 0.66), diagnosis (p = 0.11), and follow up (mean difference 12.9 [95% CI-22.7 to 48.62]; p = 0.46). There was a difference between groups regarding the length of the resection, which was greater in patients treated with a massive bone allograft and vascularized free fibula (18 ± 5 cm) than in those treated with a massive bone allograft alone (15 ± 4 cm) (mean difference -3.09 [95% CI -5.7 to -0.4]; p = 0.02). Complications related to the procedure like infection, neurovascular compromise, and graft-related complication, such as fracture and nonunion of massive bone allograft or vascularized free fibula and implant breakage, were analyzed by chart review of these patients by an orthopaedic surgeon with experience in musculoskeletal oncology. Survival of the reconstructions that had no graft or implant replacement was the endpoint. The Kaplan-Meier test was performed for a survival analysis of the reconstruction. A p value less than 0.05 was considered significant.ResultsThe surgery was longer in patients treated with a massive bone allograft and vascularized free fibula than in patients treated with a massive bone allograft alone (10 ± 0.09 and 4 ± 0.77 hours, respectively; mean difference -6.8 [95% CI -7.1 to -6.4]; p = 0.001). Twelve of 25 patients treated with massive bone allograft and vascularized free fibula had one or more complication: allograft fracture (seven), nonunion (four), and infection (four). Twelve of 21 patients treated with massive bone allograft alone had the following complications: allograft fracture (five), nonunion (six), and infection (one). The mean functional results were 26 ± 4 in patients with a massive bone allograft and vascularized free fibula and 27 ± 2 in patients with a massive bone allograft alone (mean difference 0.75 [95% CI -10.6 to 2.57]; p = 0.39). With the numbers we had, we could not detect a difference in survival of the reconstruction between patients with a massive bone allograft and free vascularized fibula and those with a massive bone allograft alone (84% [95% CI 75% to 93%] and 87% [95% CI 80% to 94%], respectively; p = 0.89).ConclusionWe found no difference in the survival of reconstructions between patients treated with a massive bone allograft and vascularized free fibula and patients who underwent reconstruction with a massive bone allograft alone. Based on this experience, our belief is that we should reconstruct these femoral intercalary defects with an allograft alone and use a vascularized fibula to salvage the allograft only if a fracture or nonunion occurs. This approach would have resulted in about half of the patients we treated not undergoing the more invasive, difficult, and risky vascularized procedure.Level of Evidence Level III, therapeutic study.     

Treatment of allograft nonunions with recombinant human bone morphogenetic proteins (rhBMP)

Fractures and nonunions are the main complications associated with bone allografts. Although the osteogenic role of recombinant human bone morphogenetic proteins (rhBMPs) has been demonstrated in experimental models and human tibial nonunions, the results are unknown for allograft nonunions. In this study, the efficacy of rhBMPs was evaluated in nonunions of femoral allografts. The results of six allograft nonunions in five patients who underwent resection of malignant bone tumours and allograft bone transplantation were analysed one to five years following application of rhBMPs at the nonunion site. There were two osteoarticular allografts and three intercalary allografts. Of three intercalary allografts, one demonstrated nonunion at both ends. Four patients received adjuvant chemotherapy and three had additional radiation therapy. There were two allograft fracture nonunions and four nonunions at the allograft-host junction. Two allograft fracture nonunions and one nonunion at the allograft-host junction were treated with 12 mg of rhBMP-2. The remaining three nonunions were treated with 7 mg of rhBMP-7 (Osigraft). The outcome and radiological evidence of healing were evaluated at a minimal follow-up of twelve months. There was neither healing of allograft fractures nor union of allograft-host junction. There was elongation or enlargement of the callus from the host. One patient continued to develop resorption of the allograft, which led to allograft fracture. Two patients who were treated with rhBMP-7 and corticocancellous allografts developed sterile drainage. There was no tumour recurrence with the use of rhBMPs after a mean follow-up of 39+/-25 months. rhBMP's alone were not sufficient to achieve healing in allograft nonunions and fractures following wide resection including periosteum and soft tissues.     

Locked intramedullary nailing. Its application to femoral and tibial axial, rotational, lengthening, and shortening osteotomies

Interlocking nailing is an alternative method of internal fixation following corrective osteotomies for malunions or after correction of leg length inequality. Of 13 osteotomies (six femoral, seven tibial) for angular or rotational malunion, all healed following dynamic locked nailing. Eleven were considered anatomic and two had mild residual deformity. One-stage femoral lengthening was performed in 17 patients. The preferred operative technique includes a long Z-shaped osteotomy, static interlocking nailing, primary cancellous bone grafts, and one or two supplemental screws at the osteotomy site to prevent shortening following dynamization. Thirteen complications developed following one-stage lengthening of the femur, which included significant loss of length in five patients, femoral nerve palsies in four patients, three deep infections, and one nonunion. Lengthening should not exceed 4.0 cm in the femur. The recommended technique of shortening osteotomy consists of resection of a cylindric segment of bone from the distal diaphyseal metaphyseal area. Shortening should not exceed 4.5 cm in the femur or 3.0 cm in the tibia. In ten patients who were shortened, all healed, but radiologic signs of union appeared very slowly in most cases.     

Lower trabecular volumetric BMD at metaphyseal regions of weight‐bearing bones is associated with prior fracture in young girls

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump‐In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual‐energy X‐ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1–1.9) and 1.3 (1.0–1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. © 2011 American Society for Bone and Mineral Research.     

Proximal Femoral Allograft: Prognostic Indicators

Between 1972 and 1999, the Orthopedic Oncology Service treated 150 patients with resection and allograft transplantation of the proximal femur. Of the group, 121 patients had malignant tumors of the proximal femur and 29 had benign disorders. Four types of allografts were used: osteoarticular (46 patients), allograft-prosthesis (73), intercalary (20), and allograft-arthrodesis (5). Only 16% of the patients died of disease and 3% required amputation. The overall success rate for the series was 77% with the best results for the allograft prosthetic (82%) and intercalary procedures (87%). Graft infection (15 patients), allograft fracture (26 patients), and local recurrence (11 patients) most markedly affected outcome. With the exception of deaths of disease, no significant outcome difference occurred between the patients with malignant and benign disorders. In conclusion, allograft implantation especially for aggressive or malignant tumors of the proximal femur appears to be a competent system for therapy.     

Intercalary endoprosthetic reconstruction for diaphyseal bone tumours

Custom-made intercalary endoprostheses may be used for the reconstruction of diaphyseal defects following the resection of bone tumours. The aim of this study was to determine the survival of intercalary endoprostheses with a lap joint design, and to evaluate the clinical results, complications and functional outcome. We retrospectively reviewed six consecutive patients, three of whom underwent limb salvage with intercalary endoprostheses of the tibia, two of the femur, and one of the humerus. Their mean age was 42 years (28 to 64). The mean follow-up was 21.6 months (9 to 58). The humeral prosthesis required revision at 14 months owing to aseptic loosening. There were no implant-related failures. Musculoskeletal Tumour Society functional outcome scores indicated that patients achieved 90% of premorbid function. Custom intercalary endoprostheses result in reconstructions comparable with, if not better than, those of allografts. Using this design of implant reduces the incidence of early complications and difficulties experienced with previous versions.     

Changes in bone-mass after tibial shaft fracture

We studied 20 patients who had suffered tibial shaft fractures 30 months previously. The bone-mineral content in diaphyseal and metaphyseal bone of the femur and tibia was determined by photon absorptiometry. There was a moderate, but significant, deficit of bone-mineral in metaphyseal bone at the knee and distal tibia. This loss was, however, far smaller than that previously reported. Persisting bone-mineral changes in diaphyseal bone were insignificant except in the fracture area where there was a 28 per cent increase. This may indicate that bone may, under some circumstances, locally increase in strength after remodelling of the fracture.     

Changes in bone-mass after tibial shaft fracture

We studied 20 patients who had suffered tibial shaft fractures 30 months previously. The bone-mineral content in diaphyseal and metaphyseal bone of the femur and tibia was determined by photon absorptiometry. There was a moderate, but significant, deficit of bone-mineral in metaphyseal bone at the knee and distal tibia. This loss was, however, far smaller than that previously reported. Persisting bone-mineral changes in diaphyseal bone were insignificant except in the fracture area where there was a 28 per cent increase. This may indicate that bone may, under some circumstances, locally increase in strength after remodelling of the fracture.     

High-energy extracorporeal shock wave treatment of nonunions

Forty-three consecutive patients who did not have healing of tibial or femoral diaphyseal and metaphyseal fractures and osteotomies for at least 9 months after injury or surgery were examined prospectively for use of high-energy extracorporeal shock waves. Former treatment modalities (cast, external fixator, plate osteosynthesis, limitation of weightbearing) remained unchanged. In all cases a 99mTechnetium dicarboxyphosphonate regional two-phase bone scintigraphy was performed before one treatment with 3,000 impulses of an energy flux density of 0.6 mJ/mm2. Radiologic and clinical followups were done at 4-week intervals starting 8 weeks after shock wave treatment. The success criterion was bridging of all four cortices in the anteroposterior and lateral radiographic views, in oblique views, or by conventional tomography. An independent observer described bony consolidation in 31 of 43 cases (72%) after an average of 4 months (range, 2-7 months). Twenty-nine of 35 (82.9%) patients with a positive bone scan had healing of the pseudarthrosis compared with two of eight (25%) patients with a negative bone scan. Six of these eight patients with negative scans were heavy smokers. No complications were observed. High-energy shock wave therapy seemed to be an effective noninvasive tool for stimulation of bone healing in properly selected patients with a diaphyseal or metaphyseal nonunion of the femur or tibia. Additional controlled studies are mandatory.