Irradiated Bone Grafts LEONARD
MARSIOR, M.D.,Los
From the Department of SurgerylOrtbopedics, University (?f Calijornia Medical Center, Los Angeles, California. Tbis work was supported in part by grants Jrom Gamma Phi Beta Sorority, Cancer Research Fund of tbe Unizlersicy qs California, and tbe Volunteers Auxiliary of tbe University of Calijornia Medical Center, Los Angeles, CaliJornia.
suppIy of has plagued surgeons for centuries. Use of homogenous and heterogenous bone was attempted for grafting but was abandoned because of poor resuIts. Heterogenous grafts were unsuccessfu1 in most cases because of the severe inflammatory response they produce, and in genera1 they have been discarded for transpIant in man. However, homogenous grafts properIy prepared have a definite vaIue in the armamentarium of the orthopedic surgeon. HE
PROBLEM
of an adequate
T sterile bone for transpIantation
HISTORY
The first successfu1 bone transpIant was accomplished in 1887 by Macewen [I]. He removed the entire diaphysis of the humerus in a three year oId infant because of osteomyelitis and Iater transplanted bone grafts from six other patients to form a new diaphysis. Barth [2]concluded that the greater part of an autogenous bone graft underwent necrosis and replacement by the host. The demand for bone for operations was so persistent that it was inevitabIe that a bone bank be started to provide a store of bone. Ore11 [J] of Sweden began to use bone from cadavers and animals as a source. Inclan [4] realized that bone was often discarded from human operations and that it was wasted. He began to preserve bone at low temperatures in sterile jars of titrated blood or Ringer’s soIution. THE BONE
BANK
The bone bank was quickIy accepted in the United States, since other tissues had been 833
Angeles, CuliJornia
stored at Iow temperatures and transplanted successfuIIy. The purpose of a bone bank is to provide a safe, steriIe reserve suppIy of bone that obviates the cutting of grafts from the patient’s own bones which can be hazardous. When a massive tibia1 graft is taken, the donor limb may be slower in regaining its function than the injured Ieg requiring the graft; furthermore, a pathoIogic fracture of the tibia may foIIow the remova of even a smaI1 graft. In chiIdren especiaIIy it rnajr be impossibIe to obtain enough bone to fiI1 a cystic defect or to bridge major defects in the long bones. Bank bone can be an esceIIent adjunct in the open reduction of fractures in which additional bone often encourages union. Other disadvantages of the autogenous graft are that it increases the magnitude of the operative procedure and thus its Iength, it may delay ambulation and the donor site may remain pamfu1. The value of bank bone decreased for a time, since the resuIts, obtained were not as satisfactory as those reported for autogenous grafts [r]. The steriIity of the graft taken at a previous operative procedure couId not be insured, so that the fear of infection was aiways present. This could be a catastrophe in many orthopedic procedures. DeVries, Badgley, and Hartman [6] reported that as high as 20 per cent of “sterije” autopsy bone was contaminated. Freeze-drying procedures do not assure the steriIity of the grafts and actuaIIy are an excellent method of preserving bacteria. The methods utiIized for the steriIization of bone in the earIy days of bone grafting were aIso developed prior to the increase in knowIedge of the immune rejection phenomena that occur in transplantation of tissue. SteriIization methods such as boiIing and the treatment by chemicaIs or antiseptics produced severe changes in the protein structure of the graft and caused a foreign body response in the host American Journal OJ Surgery, Vdumc IO:, June rp6p
Marmor [RESULTS OFBONE
TABLE I GRAFTS IN 101 PATIENTS jucces:
Type of Operation
SfUl --
I Jnsuccessful
I. Spine fusions A. Scoliosis. B. Lumbosacral.. C. Neck.
19 14 2 ---
___
2.
TotaI Bone A. B. C. D. E.
39. cysts H umerus, Femur.. Ilium.... Tibia.... Fibula.
3 I _____4
35 9 3
I 2 I
-
-~
16
TotaI 16.............. 3. Fractures A. Radius and “Ina. B. Femur.
FIG. I. A, B-g, a typica sterilized irradiated bone graft with a discolored gIass bead in the upper Ieft hand corner which indicates that the graft has been irradiated. B, the three plastic bags in which the graft is stored.
I I --
4.
at the site of the graft [7]. This couId we11 account for the poorer resuIts obtained with bank bone in the past. The steriIization of bone grafts by high voItage cathode irradiation, introduced by Turner and associates in 1956 [8], made possibIe the modern bone bank. The method was efficient and controI very accurate. Irradiation of the graft seemed to acceIerate its incorporation into the host and to prevent some of the immune inff ammatory response. Two miIIion rep from a Van de Graaff acceIerator wiI1 steriIize a bone graft as Iong as it is not over 1.5 cm. in thickness. The use of high voltage cathode rays for the steriIization of arteria1 grafts and other products has been used wideIy since I 9s I. Bassett and associates at the New York Orthopedic HospitaI pubIished a preIiminary report in 1956 [9] and a review of their experience with cathode steriIized bone in 1959 [IO]. Their success rate of 85 per cent with a wound infection rate of 0.9 per cent is quite remarkabIe. The cathode irradiation tends to produce ionizing radiation with the resuItant moIecuIar denaturization. It is probabIe that in this manner the nucIear protein of the bacteria are affected thus producing their death. Oxidation and reduction reactions aIso occur, which tend to destroy the bacteria. SteriIization of bone by radioactive cobaIt has aIso been successfu1 as reported by DeVries and associates [6], who said that irradiated 834
TotaI 2. Leg Iengthening A. Femur..
2 2
I _-
TotaI 3,
~__
I
2
8 2
I
5. PIastic surgery A. B. C. D. E.
MandibIe.. Sternum.. Forehead. MaIar. .......... Nose. ............
I I I --
__TotaI 6. Bone A. B. C.
14.. tumors AneurysmaI.. Chondroma.. Giant ceII
I
I3 2 2 4
_
--
TotaI 8.. 7. Nonunions A. Hip. B. Femur.
I --
TotaI 5. 8. Fusions A. Wrist.... B. Hip. C. ShouIder D. Finger.
I
--
9.
Total. . Fibrous dyspIasia A. Humerus.. B. Ilium. ........... C. Femur. ..........
--
TotaI 3 IO. MisceIianeous A. ReDair surgical deiect .... r. ...... B. Rib graft ......... --
_
Total
J
L
4
Irradiated
Bone
Cathode irradiation of bone grafts was instituted in I!)~s at the University of California .\ledicaI Center. The grafts arc obtained at postmortem examinations or from operative specimens within six hours and arc cut into suitable size for packaging in three seaIed poIyethyIene bags for additiona safety. (Fig. IA and B.) The grafts are immediateIy frozen and then Aown to Massachusetts Institute of ‘TechnoIogy where they are irradiated anc1 then returned in a frozen state. CuItures are taken from a contro1 package; and if these are reported negative at one week for anaerobic and aerobic bacteria, the bone is reIeased from the bank. Bone can be stored in this manner for six months at a temperature of -2O’F.
that had the highest rate of SUCC‘W. \V:LSthe unicamera1 bone cyst. In sixteen casts rcxported,
there were sixteen cases of heaIed with bank bone. (Fig. 2A and B.)
RESULTS
were no infections due to bone grafts at the MedicaI Center. Three cases were reportecl by surgeons elsewhere in the communit,y. One case became infected in a spina fusion for scoIiosis, and the organisms cuhured were a StaphyIococcus coaguIase positive and a beta hemoIytic Streptococcus. It is of interest that neither organism was present in the preirradiation cuIture. It is of interest aIso that this patient was reported to have had a tempera-
B
A 3.
c)~sts filled
Operative infection versus infection clue to the bone graft is often diffIcuIt to distinguish, aIthough in these cases every eflort w:ts Jmde the cause of any infection. There to determine
Up to the present time, 714 bone grafts have been utiIized in surgica1 procedures. (TabIe I.) This review wiI1 cover IOI patients in whom approximateIy 329 bone grafts were used. The bone was suppIied to a number of surgeons throughout the area. Grafts were packed in dry ice and were maiIed by air express to various parts of the state for use in a variety of procedures. A questionnaire was suppIied to the surgeons who operated eIsewhere than at the MedicaI Center. In these 101 patients, the rate of success of the operations in which bank bone was used was 92 per cent. The Iesion
FIG.
Grafts
C
A, fracture of the femur in young coIIege student. B, because of inability to con-
trol fracture in traction, open reduction was performed with the addition of bank bone. C, patient one and one-haIf years after the operation with massive calIus.
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Marmor of a dowe cortica1 Iength. (Fig. 4.)
graft
to
maintain
the
SUMMARY
The use of frozen irradiated bone grafts in orthopedic procedures can give a high percentage of successful resuIts without the hazard of infection. Acknowledgment: I wouId Iike to express my sincere thanks to Dr. Andrew Bassett for a11 his assistance and advice in this project, without which it wouId not have been possibIe, and aIso to Miss Patricia Payne for her devoted assistance.
FIG. 4. Dowel type bone graft of cortical bone used for leg lengthening procedure. Additional autogenous grafts shouId be added to this type of procedure because of the forces acting on the graft.
REFERENCES I. MACEWEN, W. The Growth of Bone. Observations on Osteogenesis. An Experimental Inquiry into the DeveIopment and Reproduction of Ciaphyseal Bone. Glasgow, 1912. James MacIehose and Sons. 2. BARTH, A. Ueber osteopIastik. Arch. klin. Cbir., 86: 859, 1908. 3. ORELL, S. SurgicaI bone grafting mith “OS purum,” “OS novum,” and “boiled bone.” J. Bone @ Joint Surg., 19: 873, 1937. A. The use of preserved bone graft in 4. INCLAN, orthopaedic surgery. J. Bone ti Joint Surg., 24: 81, 1942. 5. BRAY, E. A. A comparative cIinica1 study of autogenous and frozen homogenous bone in grafting procedures. Clin. Ortb., 3: 163, 1954. 6. DEVRIES, P. H., BADGLEY, C. E. and HARTMAN, J. T. Radiation steriIization of homogenous bone transplants utilizing radioactive cobaIt. J. Bone w Joint Surg., 40: 187, 1958. 7. REYNOLDS, F. C., OLIVER, R. R. and RAMSAY, R. Clinical evaluation of merthiolate bone bank and homogenous bone grafts. J. Bone IY Joint Surg.,
ture and red throat six days before her operation. Eight other patients received bone from this autopsy without an infection. There is a reasonabIe doubt in this case that the bone pIayed any roIe in the infection. One other infection was reported by a surgeon who used a bone graft in an extensive spina fusion with Harrington rods. Drainage occurred but it heaIed without incident. The wound infection rate, therefore, is less than I per cent in these cases. This compares very favorably with other banks of irradiated bone in the United States. COMMENTS
Frozen irradiated bone is an exceIIent source of preserved bone for grafts in man, and Iends itself we11 to the estabIishment of a bone bank in any hospita1. The bone can be prepared IocaIIy and flown to a major center for sterilization and then can be shipped throughout the worId. The resuIts are very encouraging in the majority of surgica1 procedures. (Fig. 3.) The bone has made possibIe earIy operations in chiIdren, which wouId have been impossibIe without a bank. Several cases of Ieg Iengthening procedures have aIso been possibIe with use
33: 873. ‘9s’. TURNER, T. C., BASSETT, C. A. L., PATE, J. W., SAWYER, P. N., TRUMP, J. G. and WRIGHT, K. A. Steri!ization of preserved bone grafts by high voItage cathode irradiation. J. Bone Ed Joint Surg., 38: 862, 1956. o. BASSETT. C. A. L.. HUDCINS T. F.. TRUMP. J. G. and tiRIGHT, K: A. The cIinica1 ‘use of cathode ray steriIized grafts of cadaver bone. S. Forum, 6: 549, ‘956. IO. BASSETT, C. A. L. and PACKARD, G. A. A cIinica1 assay of cathode ray sterilized cadaver bone grafts. Acta ortb. scandinav., 28: 198, 1959.
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