Healio
Healio
May 01, 2003
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The Effect of AlloMatrix Injectable Putty on the Outcome of Long Bone Applications

ABSTRACT

Long bone defects due to nonunion or surgical excision of benign bone tumors result in areas that require rapid regeneration of local bone. This clinical and radiographic article details the results of a commercially prepared allograft demineralized bone matrix in patients with long bone voids or gaps. Of the 76 patients included for study, 41 (54%) patients were undergoing surgical intervention for removal of benign tumors or space-occupying lesions and 35 (46%) patients had long bone nonunions. AlloMatrix Injectable Putty (Wright Medical Technology, Inc, Arlington, Tenn) was used alone in 74 (97%) patients and in combination with bone marrow aspirate in two (3%) patients with tibial nonunion. Adjunctive strut allografts were used in three patients with humeral nonunion. The average time to follow-up for the combined population was 7 months (nonunion group 6 months; benign tumor group 7 months). At the most recent follow-up, radiographic evidence of the average percent of bone healing was 85.1% for the nonunion patient group and 93% for the benign tumor patient group. From this study, AlloMatrix Injectable Putty used as a bone void filler in long bone nonunions and benign tumors shows results equal to those historically reported for autograft and other materials.




The surgical excision of benign bone tumors and nonhealing fractures results in bone voids or cortical discontinuity. Surgical repair involves further dissection and devascularization in an attempt to obtain healing of the involved bone.

Autogenous cancellous bone harvested from the iliac crest has been reported as the most successful material for bone grafting.1,2 However, surgical procedures requiring harvesting of iliac crest bone graft (ICBG) introduce a variety of potential risks to the patient, including increased surgical time, increased blood loss, and increased postoperative pain, often on a chronic basis.1,3-6

Moreover, there is a limited amount of autologous bone graft available from any one site, and optimization of the harvested graft is of paramount importance. The use of allograft materials, with and without ICBG, yields results equal to autogenous bone graft in long bone defects.2,4,7-11

Materials and Methods

Between August 1999, and November 2001, a retrospective clinical review of patients grafted using AlloMatrix Injectable Putty (Wright Medical Technology, Inc, Arlington, Tenn) for filling long bone voids or nonunions was performed. AlloMatrix Injectable Putty is a bone graft material with osteoinductive and osteoconductive properties.11,12

AlloMatrix Injectable Putty is a combination of demineralized bone matrix (DBM) (86% by volume bioassayed using human SaOS cells to ensure inductivity) (AlloSource, Denver, Co) with a surgical-grade calcium sulfate carrier (OsteoSet, Wright Medical Technology, Inc). This unique combination of bioactive materials enables rapid and reliable bone repair through the process of endochondral ossification.

Candidates were included in the study based on the following criteria: a surgeon recommended cancellous bone graft as treatment, the void shape could accommodate graft material, and patients were willing to release medical data and return for postoperative follow-up.

The surgical preparation of the benign tumor areas followed standard principles using curettes and a high-speed burr. Irrigation was used to prevent heat necrosis of bone. The resulting defect comprised an open cavity bordered by healthy cortical and cancellous bone.

The cavity was then packed with a combination of putty and CaSO4 pellets, usually in a 1:3 volume ratio. If possible, the periosteum was approximated over the cortical window. The wounds were meticulously closed in layers, and a small suction drain was placed adjacent to the deep closure.

Nonunions were treated using standard internal/external fixation techniques. The periosteum or fibrous tissue surrounding the nonunion site was elevated sharply with a curved osteotome, creating an open envelope around the nonhealing area. The putty was then introduced into this area and the periosteum closed around the site. Postoperatively, patients were treated according to their original bone void or gap and the progression of healing.

Table

Clinical and radiographic assessments were performed and the most recent follow-up interval for all patients reported. We developed a bone healing index (Table) to quantify the healing progress. For a patient to be judged as healed, the numerical total of the radiographic score and clinical score had to equal a minimum of 8. Bone growth into the defect was evaluated using serial radiographs to assess visual evidence of trabeculation within the defect. Void or gap healing and the percent of bone growth was visually determined. The chi-squared test was used for statistical analysis of the results. P<.05 was deemed significant.

Results

Of the 76 patients included in the study, 41 (54%) patients were undergoing surgical intervention for removal of a benign tumor or a space-occupying lesion and 35 (46%) patients had long bone nonunions. Of the patients with benign tumors or space-occupying lesions, the locations involved the femur, 17 (41%); tibia, 11 (27%); humerus, 8 (20%); fibula, 3 (7%); and radius, 2 (5%). Long bone nonunions involved the tibia, 13 (37%); humerus, 10 (29%); ulna, 6 (17%); femur, 5 (14%); and fibula, 1 (3%).

Overall, there were 40 women (64%) and 36 men (36%) included in the study. AlloMatrix Injectable Putty was used alone in 74 (97%) patients and in combination with bone marrow aspirate (BMA) in two (3%) patients with tibial nonunion. If the volume of graft required to fill a defect was more than 2 cc, CaSO4 pellets augmented the graft. Adjunctive strut allografts were used in three patients with humeral nonunion.

The average patient age for the entire group was 34 years (8-76 years, SD=±18). For the subgroups, the average age of patients with nonunions was 45 years (18-76 years, SD=±15), and for the benign tumor patient group, the average age was 25 years (8-63 years, SD=±14). There was no statistical difference in the age between men and women for the total group (P=.154), the nonunion group (P=.141), or the benign tumor group (P=.097).

The average time to follow-up for the combined population was 7 months (nonunion group 6 months; benign tumor group 7 months). The average time to healing for the nonunion patient group was 3.5 months and for the benign tumor patient group, 4.8 months.

At the average follow-up, radiographic evidence of the percent of bone healing for the nonunion patient group was 85.1% and for the benign tumor patient group, 93%. Figures 1 and 2 show the progression of graft incorporation at each time period for each patient subset.

Figure 1A Figure 1B Figure 1C
Figure 1. Radiograph of a 24-year-old man with a closed femoral fracture (A). At 3 weeks, he underwent intramedullary rodding and application of AlloMatrix Injectable Putty (B). At 3 months postoperative, the fracture healed with evidence of remodeling (C). Also at this time, the patient resumed normal activities.
Figure 2A Figure 2B
Figure 2. Radiograph of a 65-year-old patient with an infected nonunion of a midshaft fracture after undergoing shoulder arthroplasty (A). After insertion of a long-stem humeral prosthesis and grafting with AlloMatrix, the patient received biodegradable calcium sulfate beads with tobramycin (B). The humeral head healed, and the patient resumed normal activities.

Adverse postoperative conditions in the nonunion group included site refracture following successful healing in two patients (one femur and one tibia), one patient with hardware failure that delayed union, one patient with a postoperative neuroma over the scar area, one patient with decreased range of motion (ROM) due to site adhesions (adhesions successfully lysed with return of full ROM), and one patient with recurrent infection with evidence of self-infliction.

Of the patients with benign tumors, there were three patients who had recurrence of the tumor (one femur, one humerus, and one radius). There was one patient with a wound infection with drainage successfully treated with debridement, insertion of biodegradable CaSO4 beads with tobramycin, and intravenous antibiotics.

Five patients developed sterile wound drainage within 2 weeks postoperatively. These isolated episodes were treated prophylactically with oral antibiotics (Keflex, Eli Lilly, Indianapolis, Ind) for 2 weeks. In all patients, the drainage ceased without sequelae. There were no graft-related failures in this population.

Discussion

Successful bone void or gap healing requires a similar continuum of events that parallels host fracture healing. Autogenous cancellous bone, primarily ICBG, is commonly reported as the most successful material for bone grafting. However, surgical procedures that require autogenous harvesting introduce a variety of potential risks to patients, including increased surgical time, increased blood loss, and increased postoperative pain.

Alternative allograft substances have been introduced with successful outcomes. Also, DBM has been shown to be a reasonable bone graft substitute for filling defects and aiding in bone repair.

The bioassaying of DBM with human SaOS cells ensures the osteoinductive potential of the DBM component of the graft site. Only protein mixtures that have been shown to stimulate human bone-forming cells in culture are used.13 Previous reported studies show that when compared to autograft, bioassayed DBM and CaSO4 is an effective material for the treatment of benign bone lesions and nonhealing fractures.2,7,12-14

In a prospective study of 50 patients with benign bone lesions in which allograft was used Wilkins et al11 showed that 49 patients went on to heal in an average time of 11.8 months without graft-related complications. The single failure in this study was due to loss of fixation.

Other reported results using DBM in long bone defects have shown equally positive outcomes. Tay et al9 hypothesized that calcium sulfate as an allogenic graft carrier provides consistent resorption profiles and mechanical properties. In a study of a canine model comparing cortical autogenous graft versus DBM allograft, Dahners et al15 concluded that there was no significant difference between the groups and that DBM was an excellent osteogenic stimulant.

Tiedman et al14 showed successful use of DBM in a variety of etiologies, including nonunions and cavitary lesions. Our results show excellent radiographic evidence of healing of both nonunions and benign tumors of long bone of approximately 90% at 5 months. These results are similiar to the results of Kelly et al.12

Histological evidence of autogenous graft incorporation in long bone voids is commonly reported at 6 weeks postsurgery with complete graft conversion at 24 weeks. At the time of maturation, the DBM and CaSO4 demonstrate complete resorption. Significant callus formation is seen in both autogenous and allogenic preparations, but bone void filler such as AlloMatrix Injectable Putty eliminates potential donor site morbidity risk and fills the void or gap to avoid soft tissue adhesions. However, we reported one soft tissue adhesion at a nonunion graft site, but we did not have any graft-related complications.

Allograft tissue carries an inherent risk of disease transmission of bacterial and viral agents. To eliminate this risk of disease transmission, AlloMatrix Injectable Putty is e-beam sterilized. As opposed to gamma irradiation, which deactivates the protein growth factors, e-beam sterilization methods do not affect the osteoinductive properties of the material.13

Conclusion

This series of patients suggests that AlloMatrix Injectable Putty as bone graft filler performs similar to the gold standard of autologous bone but avoids potential risk factors and possible reoperation due to graft failure or graft harvesting site complications. AlloMatrix Injectable Putty is a safe, cost-effective bone graft substitute.

References

  1. Prolo DJ, Rodrigo JJ. Contemporary bone graft physiology and surgery. Clin Orthop. 1985; 200:322-342.
  2. Sim R, Liang TS, Tay BK. Autologous marrow injection in the treatment of delayed and non-union in long bones. Singapore Med J. 1993; 34:412-417.
  3. Arrington ET, Smith WJ, Chambers HG, Bucknell AL, Davino NA. Complications of iliac crest bone harvesting. Clin Orthop. 1996; 329:300-309.
  4. Buck BE, Malinin TI, Brown MD. Bone transplantation and human immunodrficiency virus. Clin Orthop. 1989; 240:129-136.
  5. Summers BN, Eisenstein SM. Donor site pain from the ilium. J Bone Joint Surg Br. 1989; 71:677-680.
  6. Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma. 1989; 3:192-195.
  7. Bolander ME, Galian G. The use of demineralized bone matrix in the repair of segmental defects. J Bone Joint Surg Am. 1986; 1264-1274.
  8. Salama R. Xenogenic bone grafting in humans. Clin Orthop. 1983; 174:113-121.
  9. Tay BKB, Patel VV, Bradford DS. Calcium sulfate- and calcium phosphate-based bone substitutes. Orthop Clin N Am. 1999; 30:615-623.
  10. Turner TM, Urban RM, Gitelis S, et al. Efficacy of calcium sulfate, a synthetic bone graft material, in healing large canine medullary defect. Trans Orthop Res Soc. 1999; 45:522.
  11. Wilkins RM, Kelly CM, Giusti DE. Bioassayed demineralized bone matrix and calcium sulfate: use in bone-grafting procedures. Annals Chirurgiae et Gynaecologiae. 1999; 88:180-185.
  12. Kelly CM, Wilkins RM, Gitelis S, Hartjen C, Watson T, Kim PT. The use of a surgical grade calcium sulfate as a bone graft substitute. Clin Orthop. 2001; 382:42-50.
  13. Adkisson HD, Strauss-Schoenberger J, Gillis M, Wilkins RM, Jackson M, Hruska KA. Rapid quantitative bioassay of osteoinduction. J Orthop Res. 2000; 18:503-511.
  14. Tiedeman JJ, Garvin KL, Kile TA, Connolly JF. The role of a composite, demineralized bone matrix and bone marrow in the treatment of osseous defect. Orthopedics. 1995; 18:1153-1158.
  15. Dahners LE, Jacobs RR. Long bone defects treated with demineralized bone. South Med J. 1985; 78:933-934.

Authors

From Colorado Limb Consultants and the Institute for Limb Preservation at Presbyterian-St. Luke’s Medical Center, Denver, Colo.