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Randomized trial comparing single dose versus fractionated irradiation for prevention of heterotopic bone: A preliminary report
0360-3016/90 $3.00 + .oO Copyright 0 1990 Pergamon Press plc
Its. J. Rnduuion Oncology Biol Phys., Vol. 18. pp. 1139-l 142 Printed in the U.S.A. All rights reserved.
0 Phase I/II Clinical Trial RANDOMIZED TRIAL COMPARING SINGLE DOSE VERSUS FRACTIONATED IRRADIATION FOR PREVENTION OF HETEROTOPIC BONE: A PRELIMINARY REPORT ANDRE KONSIU, M.D.,’ VINCENT PELLEGRINI, M.D.,2 COLIN POULTER, M.D.,’ JOHN DEVANNY, M.D.,2 RANDY ROSIER, M.D., PH.D.,~ C. MCCOLLISTEREVARTS,M.D.,3 MARGARET HENZLER, M.S.’ AND P. RUBIN, M.D.’ ‘Departmentof Radiation Oncology, ‘Departmentof Orthopedics,Strong Memorial NY 14642; and 30ffice of the Dean, College of Medicine,
Pennsylvania
Hospital, 601 Elmwood Avenue, Rochester, State University, P.O. Box 850, Hershey, PA 17033
Radiationtherapyhas heen shown to preventheterotopicbone formation in high risk patients undergoing total hip replacement. A number of doses have been used without a randomized trial comparing one dose regimen against another. A prospective randomized trial was undertaken comparing 10 Gy in 5 fractions versus 8 Gy in 1 fraction. Forty-seven patients have been randomized at the time of this evaluation with 37 patients eligible for analysis. The pre-operative, immediate post-operative and 2 month post-operative radiographs were graded. At the time of this analysis, 17 patients were randomized to the 8 Gy arm with 20 patients in the 10 Gy arm. Patients were treated with limited fields so as to only cover the area at risk for development of heterotopic bone to prevent adverse effects on biologic fixation of uncemented implants. When comparing the pre-operative, operative, and 2 month postoperative radiographs, only four patients (1 patient in the 8 Gy arm and 3 patients in the 10 Gy arm), had an increase in the score. No patient had an increase in score to a clinically significant level, usually grade 3 or 4. These preliminary results appear to show that 8 Gy in a single fraction can be as effective as 10 Gy in 5 fractions in preventing heterotopic bone in susceptible individuals. Further follow-up of the remaining patients may confirm this. Irradiation, Prevention of heterotopic bone, Total hip arthroplasty.
INTRODUCTION
Patients usually start irradiation on the first post-operative day with the 5 days of treatment tolerated well, but experience discomfort being transferred from the hospital bed to the simulator and treatment tables. Occasionally patients are in traction which complicates the transfers. Given this we embarked on a randomized trial comparing 8 Gy in a single fraction versus 10 Gy in 5 fractions. If found comparable this would reduce the pain and discomfort experienced by the patient and limit the chances of post-operative complications given the number of transfers the patient endures.
Radiationtherapyhas been shown to inhibit formation of heterotopic bone after total hip arthroplasty (2, 7, 13, 15, 18, 24). Various doses have been used ranging from 20 Gy in 10 fractions to 7 Gy in 1 fraction. Other modalities have been used to prevent heterotopic bone formation but with varied success (1, 10, 22). The exact mechanism responsible for the formation of heterotopic bone is unknown but dedifferentiation of mesenchymal cells is thought to be the etiologic pathway responsible (3, 4, 5, 8, 11, 17, 20, 22, 23, 25). Investigators from our institution reported that 20 Gy in 10 fractions would inhibit heterotopic bone formation if given within the first days after surgery (15). Later, Anthony et al., demonstrated that 10 Gy in 5 fractions was as effective as 20 Gy in 10 fractions in preventing heterotopic bone formation (2). Lo et al., reported that 7 Gy in one fraction was effective in preventing heterotopic bone formation compared with historical controls (13).
METHODS
AND
MATERIALS
Patients were randomized after total hip arthroplasty to receive either 8 Gy in a single fraction or 10 Gy in 5 fractions. The current period of analysis extends from January 1986 to June 1988. Irradiation started before the third post-operative day. Patients were selected for irra-
Accepted
Reprint requests to: Andre A. Konski, M.D., Radiation Therapy Department, Medical College of Ohio, C.S. #10008, Toledo. OH 43699. 1139
for publication
16 November
1989.
1140
I. J. Radiation Oncology 0 Biology 0 Physics
Table 1. Risk factors for development
of heterotopic
Pre-existing heterotopic bone in the ipsilateral (operated) contralateral hip Multiple previous hip procedures Hypertrophic osteoarthritis Diffuse idiopathic skeletal hyperostosis (DISH) Ankylosing spondylitis
bone or
diation if they had one of the risk factors listed in Table 1. The majority of patients had total hip arthroplasty but a few patients were entered into the protocol after removal of heterotopic bone which formed after surgery for previous total hip replacement, or placement of pins or plates in the hip area. The biologic fixation (porous coated) type of hip replacement was used in the majority of patients with a minority of patients having cemented prostheses (9, 14, 16, 19,2 1). Previous animal experiments from this institution have shown decreased binding of porous coated implants in rabbit tibiae after irradiation (12). This necessitated a modification in the size and placement of the fields. Figure 1 illustrates a typical field. The field is an oblique field with the superio-medial borders covering the
May 1990, Volume 18. Number 5
anterior inferior iliac spine and superior aspects of the acetabular cup. The inferior-medial border included the ischial tuberosity. The superior-lateral border included the greater trochanter and the inferior-lateral border included the lesses trochanter. Care was taken to protect as much of the prosthesis as possible while treating the above mentioned areas. The biologic fixation (porous coated) implants are dependent upon ingrowth of bone to anchor the prosthesis to the femur. Fields covering the entire implant would interfere with the ingrowth of bone and thus loosening could occur. Informed consent was obtained before treatment. Patients were treated with parallel opposed fields with either 10 or 18-MV photons. Port films were taken before treatment and on the third treatment day for the patients randomized to the 10 Gy arm. Radiographs of the treated hip were reviewed and graded according to the modified Brooker grade (Table 2) pre-operatively, immediate postoperative period, and 2 months post-operatively ( 15). The confidence interval was used to analyze if there was any statistical difference between the two groups (6). The confidence interval was computed based on a normal approximation to the binomial distribution.
Fig. 1. This radiograph illustrates the treatment field currently employed when treating a total hip arthroplasty post-operatively. The majority of the femoral shaft and acetabular cap are excluded from the treatment fields.
1141
Prevention of heterotopic bone 0 A. KONSKI et al. Table 2. Modified Brooker Grading System Grade 0 I II
III IV
No bone islands visible Islands of bone visible within soft tissues about the hips Bone spurs from the pelvis or the proximal end of the femur, but leaving at least 1 cm between opposing surfaces As in II but the space between opposing surfaces is less than 1 cm Apparent bony ankylosis
From MacLennan
et al. (15).
RESULTS Forty-seven patients have been randomized with 37 patients eligible for evaluation at this time. Of the 37 evaluable patients, 20 received 10 Cy and 17 received 8 Gy. One patient in the 8 Gy arm was lost to follow-up and another patient in the 8 Gy arm died before the 2 month follow-up with no autopsy being performed. Of the 17 patients in the 8 Gy arm, 6 were female and 11 male. Six patients had the left hip treated and 11 the right. There were two non-porous coated implants and one patient was irradiated after removal of heterotopic bone without hip arthroplasty. Nine of the patients were treated because of previous heterotopic bone and the other eight were treated because of identification of risk factors on the pre-operative radiographs of the pelvis. In the 10 Gy arm there were 4 females and 16 males with 8 left hips treated and 12 right hips treated. There were two non-porous coated implants treated. Seven patients were treated because of previous heterotopic bone and 13 because of other positive risk factors. Because some patients were treated because of positive risk factors, with no previous heterotopic bone present, and some patients did not have total removal of heterotopic bone at the time of their re-operation, accurate comparison of patients pre and post treatment scores was not possible. Residual heterotopic bone was noted on immediate post-operative radiographs 6 times in the 8 Gy arm and 5 times in the 10 Gy arm. An alternate method of analyzing the scores was employed using the differences in the scores in the immediate post-operative radiograph and the 2 month follow-up radiograph. Only l/ 17 and 3/ 20 patients in the 8 Gy and 10 Gy arms, respectively, were found to have increased scores, which could have represented post-operative progression of heterotopic bone formation. The patient in the 8 Gy arm went from a score of 0 to a score of 1. In the 10 Gy arm two patients went from scores of 1 to scores of 2 with the other patient increasing from 0 to 1. Note that, only males had increases in scores. Patients with scores of 2 or less are usually asymptomatic whereas patients with scores of 3 or 4 usually have a limited range of motion or pain.
There were no complications attributable to the radiation. One patient at the time of simulation was found to have a dislocated prosthesis likely secondary to malposition of the femoral component which had perforated the shaft. The patient recovered well after reoperation. Statistical analysis between the two groups was attempted but the patient numbers were too small for any conclusions at this time. DISCUSSION The use of radiation therapy in the prevention of heterotopic bone formation has been well documented (2, 7, 13, 15, l&24). Doses ranging from 20 Gy in 10 fractions to 7 Gy in a single fraction have been used but none have been evaluated in a prospective randomized trial. Alternative methods have also been tried with varied success (1, 10, 22). In this preliminary report we have reported on a randomized trial comparing 8 Gy in a single fraction versus 1 Gy in 5 fractions. Our preliminary results show that only one patient in the 8 Gy arm versus three in the 10 Gy arm developed an increase in the score between the post-operative radiograph and the 2 month follow-up radiograph. The single fraction arm seems to be as effective as the fractionated arm in the prevention of heterotopic bone. A single dose of radiation given in the immediate postoperative period is capable of inhibiting the development of heterotopic bone. We have previously suggested that radiation given later than the 5th post-operative day may allow heterotopic bone formation (7). Others have shown in animal models that if decalcified bone implanted in muscle is irradiated during the second post-operative week, bone development will proceed normally (5). This implies that there is a highly radiosensitive process involved in the formation of bone which is highly sensitive to irradiation, but once it occurs bone formation proceeds as if no irradiation had been given. This correlates with previous published studies in the effect of irradiation on preventing heterotopic bone formation (7). All patients had the irradiation initiated before the third post-operative day. Note that, only males developed an increase in score from the immediate post-operative period to the 2 month follow-up visit. The significance of this observation is unclear based on the preliminary
data.
CONCLUSION This preliminary report of a randomized trial comparing single versus fractionated irradiation finds the single dose to be as effective as the fractionated dose in the prevention of heterotopic bone. Future analysis of the data will be made as the treated patients reach the 2 month follow-up period.
1142
I. J. Radiation Oncology 0 Biology0 Physics
May 1990, Volume 18, Number 5
REFERENCES I. Almasbakk, K. H.; Roysland, P. Does indomethacin
2.
3. 4. 5.
6. 7.
8.
9. 10.
11. 12.
13.
prevent post-operative ectopic ossification in total hip replacement? Acta Orthop. Stand. 48556; 1977. Anthony, P.; Keys, H.; Evarts, C. M.; Rubin, P.; Lush, C. Prevention of heterotopic bone formation with early postoperative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10.00 Gy vs 20.00 Gy Schedules. Int. J. Radiat. Oncol. Biol. Phys. 13(3):365-370; 1987. Basset, C. A. L. Clinical implications of cell function in bone grafting. Clin. Orthop. 87:49-58; 1972. Brookes, M. The blood supply to bone: an approach to bone biology. London: Butterworths; 197 1. Chalmes, J.; Gray, D. H.; Rush, J. Observations on the induction of bone in soft tissue. J. Bone Joint Surg. 57B:3745; 1975. Colton, T. Statistics in medicine. Boston: Little Brown & co.; 1974. Coventry, M. B.; Scanlon, P. W. The use of radiation to discourage ectopic bone. J. Bone Joint Surg. 63A:201-208; 1981. Craven, P. L.; Urist, M. R. Osteogenesis by radioisotope labeled cell populations in implants of bone matrix under the influence of ionizing radiation. Clin Orthop. 76:23 I 243; 1971. Engh, C. A. Hip arthroplasty with a Moore prosthesis with porous coating. Clin Orthop. 176:52-665; 1983. Finerman, G. A. M. The role of Diphosphonate on heterotopic ossification after total hip arthroplasty. L. Bone Joint Surg. 59B:501; 1977. Hall, B. K. Histogenesis and morphogenesis of bone. Clin. Orthop. 74:249-255; 197 1. Konski, A.; Weiss, C.; Rosier, R.; Poulter, C.; Pelligrini, V.; Anthony, P.; Evarts, C. M.; Richardson, M.; Henzler, M.; Rubin, P. The use of post-operative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: an animal model. Int. J. Radiat. Oncol. Biol. Phys. (in press). Lo, T. C. M.; Dotter, W. E.; Pfeifer, B. A.; Wasilewski, S. A.; Torgerson, W. R.; Covil, D. J. Single dose postoperative hip irradiation in the prevention of heterotopic bone formation (Abstr.). Int. J. Radiat. Oncol. Biol. Phys. 12(Suppl 1):131-132; 1986.
14. Lord, G.; Banul, P. The Modreporic cementless total hip arthroplasty. Clin Orthop. 176:67-76; 1983. 15. MacLennan, I.; Keys, H.; Evarts, C. M.; Rubin, P. Usefulness of post-operative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients. Int. J. Radiat. Oncol. Biol. Phys. 10:49-53; 1984. 16. Morscher, E. W.; Dick, W. Cementless fixation of “Isoelastic” hip endoprosthesis manufactured from plastic materials. Clin. Otthop. 176:77-87; 1983. 17. Ostrowski, K.; Waldarski, K. Induction of heterotopic bone formation. In: G. H. Boume, ed. Biochemistry and physiology of bone, Vol. III. New York: Academic Press; 197 1: 229. 18. Parkinson, J. R.; Evarts, C. M.; Hubbard, L. F. Radiation therapy in the prevention of heterotopic ossification after total hip arthroplasty. In: The hip: Proceedings of the Tenth Open Scientific Meeting of the Hip Society. St. Louis: C. V. Mosby, Co.; 1982. 19. Pilliar, R. M. Powder metal made orthopedic implants with porous surface for fixation by tissue ingrowth. Clin. Orthop. 176:42-5 1; 1983. 20. Puzas, J. E. Endogenous factors regulated bone formation: a possible cause of heterotopic bone growth after surgery. Surg. Forum. 32:529-538; 198 1. 21. Ringe, P. A. Ring UPM total hip arthroplasty. Clin. Orthop. 176:115-123; 1983. 22. Ritter, M. A.; Gioe, T. J. The effect of indomethacin on para-articular ectopic ossification following total hip arthroplasty. Clin. Orthop. 167:113-l 17; 1982. 23. Ritter, M. D.; Vaughan, R. B. Ectopic ossification after total hip arthroplasty: Predisposing factors, frequency and effect on results. J. Bone Joint Surg. 59A:345-351; 1977. 24. Sylvester, J. E.; Greenberg, P.; Selch, M. T.; Thomas, B. J.; Amstutz, H. The use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement. Int. J. Radiat. Oncol. Biol. Phys. 14:471-476; 1988. 25. Tonna, E. A.; Cronkite, E. P. Autoradiographic studies of cell proliferation in the periosteum of intact and fractured femora of mice utilizing DNA labelling with H3 thymidine. Proc. Sot. Exp. Biol. Med. 107:719; 1961.
Its. J. Rnduuion Oncology Biol Phys., Vol. 18. pp. 1139-l 142 Printed in the U.S.A. All rights reserved.
0 Phase I/II Clinical Trial RANDOMIZED TRIAL COMPARING SINGLE DOSE VERSUS FRACTIONATED IRRADIATION FOR PREVENTION OF HETEROTOPIC BONE: A PRELIMINARY REPORT ANDRE KONSIU, M.D.,’ VINCENT PELLEGRINI, M.D.,2 COLIN POULTER, M.D.,’ JOHN DEVANNY, M.D.,2 RANDY ROSIER, M.D., PH.D.,~ C. MCCOLLISTEREVARTS,M.D.,3 MARGARET HENZLER, M.S.’ AND P. RUBIN, M.D.’ ‘Departmentof Radiation Oncology, ‘Departmentof Orthopedics,Strong Memorial NY 14642; and 30ffice of the Dean, College of Medicine,
Pennsylvania
Hospital, 601 Elmwood Avenue, Rochester, State University, P.O. Box 850, Hershey, PA 17033
Radiationtherapyhas heen shown to preventheterotopicbone formation in high risk patients undergoing total hip replacement. A number of doses have been used without a randomized trial comparing one dose regimen against another. A prospective randomized trial was undertaken comparing 10 Gy in 5 fractions versus 8 Gy in 1 fraction. Forty-seven patients have been randomized at the time of this evaluation with 37 patients eligible for analysis. The pre-operative, immediate post-operative and 2 month post-operative radiographs were graded. At the time of this analysis, 17 patients were randomized to the 8 Gy arm with 20 patients in the 10 Gy arm. Patients were treated with limited fields so as to only cover the area at risk for development of heterotopic bone to prevent adverse effects on biologic fixation of uncemented implants. When comparing the pre-operative, operative, and 2 month postoperative radiographs, only four patients (1 patient in the 8 Gy arm and 3 patients in the 10 Gy arm), had an increase in the score. No patient had an increase in score to a clinically significant level, usually grade 3 or 4. These preliminary results appear to show that 8 Gy in a single fraction can be as effective as 10 Gy in 5 fractions in preventing heterotopic bone in susceptible individuals. Further follow-up of the remaining patients may confirm this. Irradiation, Prevention of heterotopic bone, Total hip arthroplasty.
INTRODUCTION
Patients usually start irradiation on the first post-operative day with the 5 days of treatment tolerated well, but experience discomfort being transferred from the hospital bed to the simulator and treatment tables. Occasionally patients are in traction which complicates the transfers. Given this we embarked on a randomized trial comparing 8 Gy in a single fraction versus 10 Gy in 5 fractions. If found comparable this would reduce the pain and discomfort experienced by the patient and limit the chances of post-operative complications given the number of transfers the patient endures.
Radiationtherapyhas been shown to inhibit formation of heterotopic bone after total hip arthroplasty (2, 7, 13, 15, 18, 24). Various doses have been used ranging from 20 Gy in 10 fractions to 7 Gy in 1 fraction. Other modalities have been used to prevent heterotopic bone formation but with varied success (1, 10, 22). The exact mechanism responsible for the formation of heterotopic bone is unknown but dedifferentiation of mesenchymal cells is thought to be the etiologic pathway responsible (3, 4, 5, 8, 11, 17, 20, 22, 23, 25). Investigators from our institution reported that 20 Gy in 10 fractions would inhibit heterotopic bone formation if given within the first days after surgery (15). Later, Anthony et al., demonstrated that 10 Gy in 5 fractions was as effective as 20 Gy in 10 fractions in preventing heterotopic bone formation (2). Lo et al., reported that 7 Gy in one fraction was effective in preventing heterotopic bone formation compared with historical controls (13).
METHODS
AND
MATERIALS
Patients were randomized after total hip arthroplasty to receive either 8 Gy in a single fraction or 10 Gy in 5 fractions. The current period of analysis extends from January 1986 to June 1988. Irradiation started before the third post-operative day. Patients were selected for irra-
Accepted
Reprint requests to: Andre A. Konski, M.D., Radiation Therapy Department, Medical College of Ohio, C.S. #10008, Toledo. OH 43699. 1139
for publication
16 November
1989.
1140
I. J. Radiation Oncology 0 Biology 0 Physics
Table 1. Risk factors for development
of heterotopic
Pre-existing heterotopic bone in the ipsilateral (operated) contralateral hip Multiple previous hip procedures Hypertrophic osteoarthritis Diffuse idiopathic skeletal hyperostosis (DISH) Ankylosing spondylitis
bone or
diation if they had one of the risk factors listed in Table 1. The majority of patients had total hip arthroplasty but a few patients were entered into the protocol after removal of heterotopic bone which formed after surgery for previous total hip replacement, or placement of pins or plates in the hip area. The biologic fixation (porous coated) type of hip replacement was used in the majority of patients with a minority of patients having cemented prostheses (9, 14, 16, 19,2 1). Previous animal experiments from this institution have shown decreased binding of porous coated implants in rabbit tibiae after irradiation (12). This necessitated a modification in the size and placement of the fields. Figure 1 illustrates a typical field. The field is an oblique field with the superio-medial borders covering the
May 1990, Volume 18. Number 5
anterior inferior iliac spine and superior aspects of the acetabular cup. The inferior-medial border included the ischial tuberosity. The superior-lateral border included the greater trochanter and the inferior-lateral border included the lesses trochanter. Care was taken to protect as much of the prosthesis as possible while treating the above mentioned areas. The biologic fixation (porous coated) implants are dependent upon ingrowth of bone to anchor the prosthesis to the femur. Fields covering the entire implant would interfere with the ingrowth of bone and thus loosening could occur. Informed consent was obtained before treatment. Patients were treated with parallel opposed fields with either 10 or 18-MV photons. Port films were taken before treatment and on the third treatment day for the patients randomized to the 10 Gy arm. Radiographs of the treated hip were reviewed and graded according to the modified Brooker grade (Table 2) pre-operatively, immediate postoperative period, and 2 months post-operatively ( 15). The confidence interval was used to analyze if there was any statistical difference between the two groups (6). The confidence interval was computed based on a normal approximation to the binomial distribution.
Fig. 1. This radiograph illustrates the treatment field currently employed when treating a total hip arthroplasty post-operatively. The majority of the femoral shaft and acetabular cap are excluded from the treatment fields.
1141
Prevention of heterotopic bone 0 A. KONSKI et al. Table 2. Modified Brooker Grading System Grade 0 I II
III IV
No bone islands visible Islands of bone visible within soft tissues about the hips Bone spurs from the pelvis or the proximal end of the femur, but leaving at least 1 cm between opposing surfaces As in II but the space between opposing surfaces is less than 1 cm Apparent bony ankylosis
From MacLennan
et al. (15).
RESULTS Forty-seven patients have been randomized with 37 patients eligible for evaluation at this time. Of the 37 evaluable patients, 20 received 10 Cy and 17 received 8 Gy. One patient in the 8 Gy arm was lost to follow-up and another patient in the 8 Gy arm died before the 2 month follow-up with no autopsy being performed. Of the 17 patients in the 8 Gy arm, 6 were female and 11 male. Six patients had the left hip treated and 11 the right. There were two non-porous coated implants and one patient was irradiated after removal of heterotopic bone without hip arthroplasty. Nine of the patients were treated because of previous heterotopic bone and the other eight were treated because of identification of risk factors on the pre-operative radiographs of the pelvis. In the 10 Gy arm there were 4 females and 16 males with 8 left hips treated and 12 right hips treated. There were two non-porous coated implants treated. Seven patients were treated because of previous heterotopic bone and 13 because of other positive risk factors. Because some patients were treated because of positive risk factors, with no previous heterotopic bone present, and some patients did not have total removal of heterotopic bone at the time of their re-operation, accurate comparison of patients pre and post treatment scores was not possible. Residual heterotopic bone was noted on immediate post-operative radiographs 6 times in the 8 Gy arm and 5 times in the 10 Gy arm. An alternate method of analyzing the scores was employed using the differences in the scores in the immediate post-operative radiograph and the 2 month follow-up radiograph. Only l/ 17 and 3/ 20 patients in the 8 Gy and 10 Gy arms, respectively, were found to have increased scores, which could have represented post-operative progression of heterotopic bone formation. The patient in the 8 Gy arm went from a score of 0 to a score of 1. In the 10 Gy arm two patients went from scores of 1 to scores of 2 with the other patient increasing from 0 to 1. Note that, only males had increases in scores. Patients with scores of 2 or less are usually asymptomatic whereas patients with scores of 3 or 4 usually have a limited range of motion or pain.
There were no complications attributable to the radiation. One patient at the time of simulation was found to have a dislocated prosthesis likely secondary to malposition of the femoral component which had perforated the shaft. The patient recovered well after reoperation. Statistical analysis between the two groups was attempted but the patient numbers were too small for any conclusions at this time. DISCUSSION The use of radiation therapy in the prevention of heterotopic bone formation has been well documented (2, 7, 13, 15, l&24). Doses ranging from 20 Gy in 10 fractions to 7 Gy in a single fraction have been used but none have been evaluated in a prospective randomized trial. Alternative methods have also been tried with varied success (1, 10, 22). In this preliminary report we have reported on a randomized trial comparing 8 Gy in a single fraction versus 1 Gy in 5 fractions. Our preliminary results show that only one patient in the 8 Gy arm versus three in the 10 Gy arm developed an increase in the score between the post-operative radiograph and the 2 month follow-up radiograph. The single fraction arm seems to be as effective as the fractionated arm in the prevention of heterotopic bone. A single dose of radiation given in the immediate postoperative period is capable of inhibiting the development of heterotopic bone. We have previously suggested that radiation given later than the 5th post-operative day may allow heterotopic bone formation (7). Others have shown in animal models that if decalcified bone implanted in muscle is irradiated during the second post-operative week, bone development will proceed normally (5). This implies that there is a highly radiosensitive process involved in the formation of bone which is highly sensitive to irradiation, but once it occurs bone formation proceeds as if no irradiation had been given. This correlates with previous published studies in the effect of irradiation on preventing heterotopic bone formation (7). All patients had the irradiation initiated before the third post-operative day. Note that, only males developed an increase in score from the immediate post-operative period to the 2 month follow-up visit. The significance of this observation is unclear based on the preliminary
data.
CONCLUSION This preliminary report of a randomized trial comparing single versus fractionated irradiation finds the single dose to be as effective as the fractionated dose in the prevention of heterotopic bone. Future analysis of the data will be made as the treated patients reach the 2 month follow-up period.
1142
I. J. Radiation Oncology 0 Biology0 Physics
May 1990, Volume 18, Number 5
REFERENCES I. Almasbakk, K. H.; Roysland, P. Does indomethacin
2.
3. 4. 5.
6. 7.
8.
9. 10.
11. 12.
13.
prevent post-operative ectopic ossification in total hip replacement? Acta Orthop. Stand. 48556; 1977. Anthony, P.; Keys, H.; Evarts, C. M.; Rubin, P.; Lush, C. Prevention of heterotopic bone formation with early postoperative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10.00 Gy vs 20.00 Gy Schedules. Int. J. Radiat. Oncol. Biol. Phys. 13(3):365-370; 1987. Basset, C. A. L. Clinical implications of cell function in bone grafting. Clin. Orthop. 87:49-58; 1972. Brookes, M. The blood supply to bone: an approach to bone biology. London: Butterworths; 197 1. Chalmes, J.; Gray, D. H.; Rush, J. Observations on the induction of bone in soft tissue. J. Bone Joint Surg. 57B:3745; 1975. Colton, T. Statistics in medicine. Boston: Little Brown & co.; 1974. Coventry, M. B.; Scanlon, P. W. The use of radiation to discourage ectopic bone. J. Bone Joint Surg. 63A:201-208; 1981. Craven, P. L.; Urist, M. R. Osteogenesis by radioisotope labeled cell populations in implants of bone matrix under the influence of ionizing radiation. Clin Orthop. 76:23 I 243; 1971. Engh, C. A. Hip arthroplasty with a Moore prosthesis with porous coating. Clin Orthop. 176:52-665; 1983. Finerman, G. A. M. The role of Diphosphonate on heterotopic ossification after total hip arthroplasty. L. Bone Joint Surg. 59B:501; 1977. Hall, B. K. Histogenesis and morphogenesis of bone. Clin. Orthop. 74:249-255; 197 1. Konski, A.; Weiss, C.; Rosier, R.; Poulter, C.; Pelligrini, V.; Anthony, P.; Evarts, C. M.; Richardson, M.; Henzler, M.; Rubin, P. The use of post-operative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: an animal model. Int. J. Radiat. Oncol. Biol. Phys. (in press). Lo, T. C. M.; Dotter, W. E.; Pfeifer, B. A.; Wasilewski, S. A.; Torgerson, W. R.; Covil, D. J. Single dose postoperative hip irradiation in the prevention of heterotopic bone formation (Abstr.). Int. J. Radiat. Oncol. Biol. Phys. 12(Suppl 1):131-132; 1986.
14. Lord, G.; Banul, P. The Modreporic cementless total hip arthroplasty. Clin Orthop. 176:67-76; 1983. 15. MacLennan, I.; Keys, H.; Evarts, C. M.; Rubin, P. Usefulness of post-operative hip irradiation in the prevention of heterotopic bone formation in a high risk group of patients. Int. J. Radiat. Oncol. Biol. Phys. 10:49-53; 1984. 16. Morscher, E. W.; Dick, W. Cementless fixation of “Isoelastic” hip endoprosthesis manufactured from plastic materials. Clin. Otthop. 176:77-87; 1983. 17. Ostrowski, K.; Waldarski, K. Induction of heterotopic bone formation. In: G. H. Boume, ed. Biochemistry and physiology of bone, Vol. III. New York: Academic Press; 197 1: 229. 18. Parkinson, J. R.; Evarts, C. M.; Hubbard, L. F. Radiation therapy in the prevention of heterotopic ossification after total hip arthroplasty. In: The hip: Proceedings of the Tenth Open Scientific Meeting of the Hip Society. St. Louis: C. V. Mosby, Co.; 1982. 19. Pilliar, R. M. Powder metal made orthopedic implants with porous surface for fixation by tissue ingrowth. Clin. Orthop. 176:42-5 1; 1983. 20. Puzas, J. E. Endogenous factors regulated bone formation: a possible cause of heterotopic bone growth after surgery. Surg. Forum. 32:529-538; 198 1. 21. Ringe, P. A. Ring UPM total hip arthroplasty. Clin. Orthop. 176:115-123; 1983. 22. Ritter, M. A.; Gioe, T. J. The effect of indomethacin on para-articular ectopic ossification following total hip arthroplasty. Clin. Orthop. 167:113-l 17; 1982. 23. Ritter, M. D.; Vaughan, R. B. Ectopic ossification after total hip arthroplasty: Predisposing factors, frequency and effect on results. J. Bone Joint Surg. 59A:345-351; 1977. 24. Sylvester, J. E.; Greenberg, P.; Selch, M. T.; Thomas, B. J.; Amstutz, H. The use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement. Int. J. Radiat. Oncol. Biol. Phys. 14:471-476; 1988. 25. Tonna, E. A.; Cronkite, E. P. Autoradiographic studies of cell proliferation in the periosteum of intact and fractured femora of mice utilizing DNA labelling with H3 thymidine. Proc. Sot. Exp. Biol. Med. 107:719; 1961.