The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 87, Issue 2

Scientific Articles | February 01, 2005

Optimal Timing of Preoperative Radiation for Prophylaxis Against Heterotopic Ossification: A Rabbit Hip Model

Mustasim N. Rumi, MD¹; Gurvinder S. Deol, MD¹; Jason A. Bergandi, MD¹; Kishor P. Singapuri, MD²; Vincent D. PellegriniJr., MD³

¹ Department of Orthopaedics and Rehabilitation and the Musculoskeletal Research Laboratory, the Milton S. Hershey Medical Center of the Pennsylvania State University College of Medicine, P.O. Box 850, MCH089, Hershey, PA 17033
² Lancaster General Health Campus, 2102 Harrisburg Pike, Lancaster, PA 17603
³ Department of Orthopaedics, University of Maryland School of Medicine, 22 South Greene Street, Suite S11B, Baltimore, MD 21201. E-mail address: vpellegrini@umoa.umm.edu

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In support of their research or preparation of this manuscript, one or more of the authors received Grant 95-027 from the Orthopaedic Research and Education Foundation. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Investigation performed at the Department of Orthopaedics and Rehabilitation and the Musculoskeletal Research Laboratory, the Milton S. Hershey Medical Center of the Pennsylvania State University College of Medicine, Hershey, Pennsylvania

The Journal of Bone and Joint Surgery, Incorporated

J Bone Joint Surg Am, 2005 Feb 01;87(2):366-373. doi: 10.2106/JBJS.C.00974

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Abstract

Background: In a previous study, we developed a rabbit model of heterotopic ossification and demonstrated that 800 or 1200 cGy of radiation before an operation on the hip significantly decreased postoperative ectopic bone formation compared with that seen after the operation on the non-irradiated, contralateral hip. The purpose of this study was to determine the optimal preoperative timing of radiation prophylaxis against heterotopic ossification following hip surgery in this same experimental model.

Methods: Seventy-two hips in thirty-six New Zealand White rabbits were divided into four treatment groups corresponding to four preoperative points in time (four hours, twenty-four hours, seventy-two hours, and three weeks). The hips were irradiated with 1200 cGy at the different preoperative time points (eighteen hips at each time) to investigate the efficacy of the four preoperative radiation protocols. The rabbits then underwent bilateral hip surgery. They were killed and radiographs were made four months postoperatively. Heterotopic ossification was graded according to a modification of the scale of Brooker et al. The mean grade, the interobserver and intraobserver reliability, and the significance (p < 0.05) of the differences between the groups were evaluated.

Results: Radiation delivered at twenty-four hours preoperatively was significantly more effective for prophylaxis against heterotopic ossification than was radiation delivered at four hours or seventy-two hours preoperatively (p < 0.05), and the difference between the twenty-four-hour and three-week groups approached significance (p = 0.088). Furthermore, the twenty-four-hour group had a significantly lower percentage of hips with high-grade heterotopic ossification than did the four-hour (p = 0.02), seventy-two-hour (p = 0.002), and three-week (p = 0.03) groups.

Conclusions: Preoperative irradiation to prevent heterotopic ossification optimally should be administered twenty-four hours before the operation. This latency period probably allows expression of radiation-induced sublethal mutations in the genetic code of pluripotential stem cells and precludes differentiation to osteoblastic cell lines.

Clinical Relevance: If the findings of this study are validated in human clinical trials, they may allow preoperative outpatient radiation prophylaxis for patients at risk for heterotopic ossification. This approach would minimize patient discomfort and eliminate the risk of prosthetic hip dislocation associated with transport and positioning of the patient for radiation therapy in the early postoperative period.

Figures in this Article

Heterotopic ossification compromises the success of total hip arthroplasty. Nearly 10% of patients with heterotopic ossification experience functional impairment such as pain and a decreased range of motion related to the inflammatory reaction that accompanies this condition^1-5. Prophylactic methods aimed at inhibiting heterotopic ossification have included pharmacological measures and radiation therapy^6-19.

Prophylactic irradiation of the hip and surrounding soft tissue has been used successfully to reduce heterotopic ossification. Limited-field radiation therapy can exclude the ingrowth surface of the implant to avoid any adverse effect on the biologic fixation of the prosthesis^4,13,20-24. When administered at the recommended dose, radiation has had negligible systemic effects and therefore has become an increasingly popular modality among joint replacement surgeons. Studies have suggested that preoperative radiation therapy is equivalent to postoperative irradiation for prophylaxis against heterotopic ossification^{13,20,23,25-30}.

In a previously developed rabbit model, which also serves as the basis for our current investigation, we evaluated the effect of preoperative irradiation on heterotopic ossification in a setting similar to the human condition in hip surgery³¹. In that model, a single limited-field dose of 800 or 1200 cGy delivered to the hip joint provided effective prophylaxis against heterotopic ossification. Furthermore, such treatment was equally effective regardless of whether it was administered twenty-four hours preoperatively or postoperatively. In a rat model, Kantorowitz et al. demonstrated that radiation was more effective when it was delivered one hour preoperatively than when it was delivered forty-eight hours preoperatively²⁷. In a human clinical trial, radiation delivered within six hours following an operation was unexpectedly found to be less effective than radiation given six or forty-eight hours preoperatively²³. The optimal time for maximal efficacy of radiation delivered in the preoperative setting remains to be defined.

The purpose of the current investigation was to determine the ideal preoperative time for administration of radiation therapy for prophylaxis against heterotopic ossification following hip surgery. In our New Zealand White rabbit model, we compared the efficacy of radiation delivered at four preoperative time points, ranging from four hours to three weeks, for prevention of heterotopic ossification after hip surgery.

Materials and Methods

Materials and Methods | Results | Discussion | Acknowledgements | References

This investigation was approved by the Institutional Animal Care and Use Committee.

Experimental Design

Thirty-six 3-kg male New Zealand White rabbits (seventy-two hips) were randomly assigned to a balanced incomplete-block-design experimental protocol. Each hip of each rabbit was irradiated at one of four defined preoperative time points. Rabbits were randomized to include an equal number of left and right hips in each block. In this manner, eighteen hips were treated at each preoperative time point (four hours, twenty-four hours, seventy-two hours, and three weeks) (Table I). This balanced incomplete block design ensured that no animal would receive the same radiation treatment in both hips and that each protocol was equally paired against each of the other three protocols. The resulting incomplete block design produced six groups of six rabbits each receiving the same treatment, which allowed for enhanced data analysis that increased the statistical power of the experiment while also providing intrarabbit protocol analysis. The selection of the time points was intended to span previously studied periods and to encompass a broader spectrum of radiation-treatment effects.

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TABLE I Randomized Block Design Allocating Thirty-six Animals, Irradiated at Four Different Intervals, into Six Study Groups to Avoid Identical Treatment in Both Hips of the Same Rabbit

Preop. Times of Irradiation	No. of Rabbits
4 hr and 24 hr	6
4 hr and 72 hr	6
4 hr and 3 wk	6
24 hr and 72 hr	6
24 hr and 3 wk	6
72 hr and 3 wk	6
Total	36

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TABLE I Randomized Block Design Allocating Thirty-six Animals, Irradiated at Four Different Intervals, into Six Study Groups to Avoid Identical Treatment in Both Hips of the Same Rabbit

Preop. Times of Irradiation	No. of Rabbits
4 hr and 24 hr	6
4 hr and 72 hr	6
4 hr and 3 wk	6
24 hr and 72 hr	6
24 hr and 3 wk	6
72 hr and 3 wk	6
Total	36

The bilateral hip surgery was timed to maintain the preplanned preoperative radiation time point for each hip. The rabbits were killed and radiographs were made at four months postoperatively to determine the severity of heterotopic ossification according to a modification of the grading scale described by Brooker et al.³² (Fig. 1).

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Fig. 1: Modification of the scale described by Brooker et al.³² for grading heterotopic ossification in rabbits. Grade 0: no heterotopic bone formation (not shown). Grade I: faint osseous islands in the soft tissues around the joint. Grade II: heterotopic bone occupying <50% of the space between the greater trochanter and the acetabulum. Grade III: heterotopic bone occupying >50% of the space between the greater trochanter and the acetabulum. Grade IV: total or nearly total ankylosis (bone to within 1.0 mm of either side of the greater trochanter and the acetabulum). (Reprinted, with permission, from: Schneider DJ, Moulton MJ, Singapuri K, Chinchilli V, Deol GS, Krenitsky G, Pellegrini VD Jr. Inhibition of heterotopic ossification with radiation therapy in an animal model. Clin Orthop.1998;355: 39.)

Radiation Protocol

A Clinac-2300 C/D unit (Varian, Palo Alto, California) with 6-MV photons was used to deliver 1200 cGy of radiation to the hips at the specified times. The rabbits were irradiated while sedated and lying prone on a custom board designed to stabilize and position the hindquarters. Treatments were carried out with a posteriorly applied field with a source-to-skin distance of 100 cm. Each rabbit underwent simulated treatment prior to the actual treatment, and a confirmation radiograph (port film) was obtained after the rabbit was transferred to the treatment machine. Exposure to the radiation beam was limited to a 3.0-cm by 3.0-cm square centered over the hip and included the femoral head, the greater trochanter (including the reaming portal), and the hip abductor muscles (Fig. 2).

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Fig. 2: The radiation field included the hip joint, trochanters, and abductor muscles.

Surgical Protocol

After induction of general anesthesia and endotracheal intubation, the rabbits were placed onto a custom surgical board that allowed full immobilization and ideal positioning for bilateral hip surgery. Each hindquarter was shaved, prepared, and draped in a sterile fashion. The surgical approach was identical bilaterally and was designed to mimic the approach for a total hip arthroplasty in a human, as previously described³¹. A 2.5-cm skin incision was made over the greater trochanter, and the dissection was carried down to bone through the gluteus maximus, splitting the muscle in the direction of its fibers. The abductor muscles were dissected to expose the greater trochanter. A pneumatic drill with a 2.5 to 4.0-mm bit was used to enter the medullary canal, which was then serially reamed by hand with incrementally larger wire brushes to 4.0 to 5.0 mm. The debris created by the reaming was left in situ within the surgical wound, with no effort made to clear it with irrigation. Ischemic injury to the abductor muscles was induced by applying a Kelly clamp for three minutes during the procedure. The wound was closed in layers. An immediate postoperative radiograph was used to verify that the femur was not fractured. Postoperative analgesia protocols were guided by our institutions' veterinarians and did not include anti-inflammatory agents. The rabbits were permitted to eat and walk ad libitum.

Radiographic Analysis

Radiographs were made at four months postoperatively, which had been previously determined as sufficient time for maturation of heterotopic ossification to allow reliable radiographic staging³¹. Radiographs were made with the rabbits anesthetized and secured in the prone position with the knees together on a specially designed board to provide a clear and reproducible image for study. The heterotopic ossification was graded with a modification of the scale described by Brooker et al.³² (Fig. 1).

Each radiograph was independently analyzed by two observers who were blinded to the timing of the preoperative irradiation. Each radiograph was analyzed at three different times by each observer so that we could assess intraobserver reproducibility. Final consensus grading was then performed with both reviewers analyzing the radiographs together and assigning a single grade to each hip on the basis of their previous independent interpretations. The reliability of this technique in this experimental setting was previously determined with the kappa statistic³¹.

Statistical Analysis

Sample size was calculated for a power of 0.80. Statistical analysis was performed to establish the optimal preoperative timing of the radiation to prevent heterotopic ossification. The Fleiss weighted kappa statistic was used to assess the reliability of the review process. Kappa values between 0.6 and <0.8 were considered to indicate "substantial" agreement, and values between 0.8 and 1.0 were considered to indicate "almost perfect" agreement according to Fleiss's criteria. Comparisons of the mean grades of the heterotopic ossification among the four time-point groups were performed with use of PROC MIXED in SAS (SAS Institute, Cary, North Carolina) with the LSMEANS sub-command for unbalanced data and multiple comparisons with use of the TUKEY option. The standard error of the mean and the 95% confidence intervals were calculated. Additionally, the hips in each group were subdivided on the basis of the severity of the heterotopic ossification in order to determine the ratios of hips with less severe heterotopic ossification (grades 0, I, and II) to those with more severe heterotopic ossification (grades III and IV). These ratios were compared between groups with the Friedman chi-square test. P values of <0.05 were considered significant for both analyses.

Results

Materials and Methods | Results | Discussion | Acknowledgements | References

Five rabbits died in the perioperative period, and a veterinarian performed necropsy studies on those rabbits. One of the five rabbits was killed immediately postoperatively because of an iatrogenic femoral fracture that was detected by routine postoperative radiography. Two of the rabbits died from anesthetic-related complications, and two others died of pulmonary complications immediately postoperatively. Each of these rabbits was replaced by a rabbit that had been irradiated at the appropriate preoperative time points to maintain the desired number of animals in each group at the beginning of the experiment. There were no infections or wound complications. For the final radiographic analysis at four months, eighteen hips were available in the four-hour group; eighteen, in the twenty-four-hour group; sixteen, in the seventy-two-hour group; and seventeen, in the three-week group. Unbalanced data were adjusted by the least-squares-means method. All rabbits that were alive at the time of the analysis at four months had had an unremarkable postoperative course. The Fleiss weighted kappa statistic was 0.964, indicating "almost perfect" intraobserver agreement within the two sets of ratings.

Comparison of the Mean Grades for Heterotopic Ossification

The twenty-four-hour group showed the least amount of heterotopic ossification (mean grade, 1.8 compared with 2.8 for the four-hour group, 2.8 for the seventy-two-hour group, and 2.7 for the three-week group) (Table II; Figs. 3 and 4). There was a significant difference between the twenty-four-hour and four-hour groups (p < 0.05) and between the twenty-four-hour and seventy-two-hour groups (p = 0.049), whereas the difference between the twenty-four-hour and three-week groups approached significance (p = 0.088). There was no significant difference between the four-hour and seventy-two-hour groups (p < 0.999), between the four-hour and three-week groups (p < 0.997), or between the seventy-two-hour and three-week groups (p < 0.992). There were no qualitative differences in the radiographic appearance of heterotopic bone of equal grade among the four groups.

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TABLE II Grade of Heterotopic Ossification in Each Group^*

	Grade of Heterotopic Ossification
Preop. Times of Irradiation	Mean	Standard Error	95% Confidence Interval
4 hr	2.764	0.25	2.274, 3.254
24 hr	1.833	0.25	1.343, 2.323
72 hr	2.797	0.265	2.278, 3.316
3 wk	2.691	0.257	2.187, 3.195

Irradiation at twenty-four hours preoperatively resulted in the least heterotopic ossification.

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TABLE II Grade of Heterotopic Ossification in Each Group^*

	Grade of Heterotopic Ossification
Preop. Times of Irradiation	Mean	Standard Error	95% Confidence Interval
4 hr	2.764	0.25	2.274, 3.254
24 hr	1.833	0.25	1.343, 2.323
72 hr	2.797	0.265	2.278, 3.316
3 wk	2.691	0.257	2.187, 3.195

Irradiation at twenty-four hours preoperatively resulted in the least heterotopic ossification.

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Fig. 3: Irradiation at twenty-four hours prior to the operation was the most effective for prophylaxis against heterotopic ossification.

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Fig. 4: Comparison of a hip in the twenty-four-hour group (left, with grade-0 heterotopic ossification) with one in the seventy-two-hour group (right, with grade-III heterotopic ossification) demonstrates superior efficacy of the radiation administered twenty-four hours prior to the operation.

Comparison of Low and High-Grade Heterotopic Ossification

Analysis with the Friedman chi-square test showed that the twenty-four-hour group had significantly more hips with low-grade (grade-0, I, or II) heterotopic ossification (fourteen hips with low-grade compared with four with high-grade [grade-III or IV] heterotopic ossification) than did the four-hour group (p = 0.02), the seventy-two-hour group (p = 0.002), or the three-week group (p = 0.03) (Table III). The other three groups were similar to one another with regard to the numbers of hips with low and high-grade heterotopic ossification (seven low-grade and eleven high-grade in the four-hour group, four low-grade and twelve high-grade in the seventy-two-hour group, and seven low-grade and ten high-grade in the three-week group). There was no significant difference in the ratio of less severe to more severe heterotopic ossification between the four-hour and seventy-two-hour groups (p = 0.39), between the four-hour and three-week groups (p = 0.89), or between the seventy-two-hour and three-week groups (p = 0.33).

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TABLE III Hips with High and Low-Grade Heterotopic Ossification in Each Group^*

	No. of Hips with Heterotopic Ossification
Preop. Times of Irradiation	Grades 0, I, and II	Grades III and IV	Total
4 hr	7	11	18
24 hr	14	4	18
72 hr	4	12	16
3 wk	7	10	17

Irradiation at twenty-four hours preoperatively resulted in fewer hips with severe heterotopic ossification than did irradiation at four hours, seventy-two hours, or three weeks preoperatively.

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TABLE III Hips with High and Low-Grade Heterotopic Ossification in Each Group^*

	No. of Hips with Heterotopic Ossification
Preop. Times of Irradiation	Grades 0, I, and II	Grades III and IV	Total
4 hr	7	11	18
24 hr	14	4	18
72 hr	4	12	16
3 wk	7	10	17

Irradiation at twenty-four hours preoperatively resulted in fewer hips with severe heterotopic ossification than did irradiation at four hours, seventy-two hours, or three weeks preoperatively.

Discussion

Materials and Methods | Results | Discussion | Acknowledgements | References

Heterotopic ossification following hip surgery is an important complication that potentially causes heavy burdens on individuals and society. Pain and limited mobility compromise maximal functional recovery following the total hip arthroplasty. Progression of the heterotopic ossification may lead to joint ankylosis and eventually to revision surgery^3,5. Despite its high prevalence and multiple clinical studies of the complication, the pathophysiology of heterotopic ossification remains unclear^15,33-41. Nonetheless, both local and systemic measures have been established to provide effective prophylaxis against heterotopic ossification following hip surgery^{6-14,16-19,33-45}. Although nonsteroidal anti-inflammatory agents are effective in preventing heterotopic ossification, systemic and local gastrointestinal side-effects often limit their usefulness^8,11,16,46. Inconsistent compliance by patients, the anti-platelet effect complicating use with pharmacologic thromboprophylaxis, and aggravation of underlying renal dysfunction are problems with use of these drugs. Finally, their adverse impact on bone-healing is a matter of concern as inhibition of ingrowth of bone into cementless prostheses can lead to mechanical component failure^21,47.

Conversely, limited-field radiation prophylaxis enables localization of its inhibitory effect on bone formation while avoiding systemic complications^{13,20,22-24,48-50}. Precise irradiation of the target tissue while minimizing the exposure of surrounding tissue is possible; a point 1.0 cm from the radiation field receives <5% of the delivered dose⁵⁰. Moreover, radiation has been shown to be highly effective prophylaxis against heterotopic ossification following hip surgery^22-26,28-30. Clinical and animal studies have suggested that preoperative and postoperative irradiation have comparable efficacy^22-24,27-30. For reasons of patient comfort and safety (for example, to avoid prosthetic hip dislocation during transport and positioning of the patient in the radiation suite), it is desirable to administer radiation treatment preoperatively. One of us (V.D.P. Jr.) and Gregoritch confirmed that radiation therapy delivered shortly (6.1 hours) before surgery provided prophylaxis that was comparable with that provided by postoperative irradiation (up to 51.3 hours after surgery)²³. An incidental observation was a threefold greater prevalence of heterotopic ossification in patients irradiated within four hours before hip arthroplasty, suggesting that the optimal time to administer preoperative radiation for prophylaxis against heterotopic ossification was not necessarily closest to the time of the operation. Prior studies of preoperative radiation for prevention of heterotopic ossification in animals have yielded variable results. Rats that had received irradiation forty-eight hours preoperatively had significantly (p < 0.03) more heterotopic ossification than those that had received it one hour preoperatively²⁷. In a study of rabbits, it was incidentally observed that irradiation twenty-four hours preoperatively was more effective than radiation four hours preoperatively³¹.

Animal models have been utilized to investigate radiation prophylaxis against heterotopic ossification more rigorously and systematically^51-53. Kantorowitz et al. showed that irradiation administered one hour preoperatively was comparable with that administered forty-eight hours postoperatively for prophylaxis against heterotopic ossification in a rat model²⁷; however, the model involved a nonphysiological abdominal pouch used for implantation of exogenous material (decalcified rat-bone matrix) to stimulate heterotopic ossification. We developed an alternative and more physiological model in which reaming of the femoral canal generated heterotopic ossification about the hip in a manner similar to the human clinical condition following hip arthroplasty and intramedullary nailing of the femur³¹. We used New Zealand White rabbits because they are easy to maintain and because of similarities between their and human bone physiology and the facility with which they make bone^47,53-58.

Since our prior work had demonstrated that irradiation administered four and twenty-four hours preoperatively was superior to no irradiation, a control group of untreated rabbits was considered to be redundant by our institutional animal experimentation committee and was not used in the present study. Of the four preoperative time points in the current investigation, irradiation of the hip twenty-four hours preoperatively resulted in the least amount of heterotopic ossification, whereas the grades of heterotopic ossification were similar among the four-hour, seventy-two-hour, and three-week groups. Analysis of the ratios of low-grade (0, I, and II) to high-grade (III and IV) heterotopic ossification in the groups further supported the superior efficacy of the treatment given twenty-four hours preoperatively. Authors of clinical studies of prophylaxis against heterotopic ossification^5-8,12,17,18 have commonly reported the frequency of heterotopic ossification on the basis of two classifications of severity (grades I and II compared with grades III and IV). A similar analysis of our data showed an even stronger advantage of radiation administered twenty-four hours preoperatively as opposed to four hours (p = 0.02), seventy-two hours (p = 0.002), or three weeks (p = 0.03) preoperatively. A prior study of the same animal model showed inferior efficacy of radiation delivered at two, three, or five days preoperatively compared with that delivered at twenty-four hours preoperatively³¹. Collectively, human clinical trials and animal model data consistently suggest that the optimal time for preoperative prophylactic irradiation to prevent heterotopic ossification about the hip is twenty-four hours before the operation, with decreasing efficacy observed with treatment administered at sixteen and forty-eight hours preoperatively.

Following surgical trauma, pluripotential mesenchymal stem cells have been shown to differentiate along osteogenic precursor cell lines, with the response occurring as early as sixteen hours after injury and peaking thirty-six hours after perturbation⁵⁹. Once cellular differentiation is committed, emphasis on DNA replication diminishes and bone-forming cells become less sensitive to the effects of radiation⁶⁰. The observation that the severity of heterotopic ossification actually increases as the timing of the preoperative radiation shortens from twenty-four to four hours before the operation suggests a necessary latent period to allow for optimal efficacy of the radiation therapy. It is known that large doses of radiation can result in direct cell death before division as a result of the effect of free radicals on essential cellular mechanisms⁵⁴. However, lower doses of radiation, as used clinically and in our study, may produce cell death only after one or more divisions. The dose of radiation employed may inflict only sublethal injury to the genetic material and allow existing osteoprogenitor cells to continue to form heterotopic bone prior to any subsequent mitotic events that express the newly incurred DNA damage. When the surgical stimulus occurs a short time following the irradiation, existing cells committed to bone formation will continue to form bone until the radiation gene damage is expressed in the next cell cycle. This definitive expression of radiation-induced sublethal genetic defects may not be apparent until the next cell division, when subsequent necrosis of pluripotent mesenchymal cells precludes the appearance of heterotopic bone.

The results in our rabbit model suggest that preoperative radiation for prophylaxis against heterotopic ossification is most effective when it is administered twenty-four hours prior to the operation. It is possible that the twenty-four-hour interval allows sufficient time for the necessary cell replication to express the injurious effects of sublethal radiation doses and prevent proliferation of osteoprogenitor cells. Conversely, radiation delivered much more than twenty-four hours prior to the surgery may be less effective because greater time is available for repair of damaged osteoprogenitor cell lines as multiple cell divisions can occur between the time of the radiation and the time of the operation. Irradiation closer to the time of the operation is also less effective as already committed osteoprogenitor cells continue to synthesize bone before the next cell division expresses radiation-induced DNA damage that will preclude further cell proliferation and protein synthesis. It is likely that low-dose irradiation of pluripotent mesenchymal stem cells twenty-four hours before an operation balances the processes of cellular replication and cellular repair to optimize the expression of damaged DNA in potential osteoprogenitor cells. It may allow sufficient time for cell replication, therefore allowing the expression of damaged DNA, while leaving inadequate time for cellular repair prior to the stimulus of the surgery. The net effect is one of pluripotent mesenchymal stem cells that are incapable of effectively responding to an osteogenic stimulus at the time of the surgery; this is manifested clinically as less heterotopic ossification. Clinical application of this knowledge may allow preoperative outpatient radiation prophylaxis for patients at risk for heterotopic ossification. This would minimize the patient discomfort and the risk of prosthetic hip dislocation that accompany transport and positioning of the patient for radiation therapy in the early postoperative period. ?

Acknowledgements

Materials and Methods | Results | Discussion | Acknowledgements | References

Note: The authors express special appreciation to C. McCollister Evarts, MD, for his pioneering investigation in the field of heterotopic ossification and his invaluable mentoring.

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Materials and Methods | Results | Discussion | Acknowledgements | References

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Topics

hip joint ; heterotopic ossification ; oryctolagus cuniculus

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Mustasim N. Rumi, Gurvinder S. Deol, Jason A. Bergandi, Kishor P. Singapuri, Vincent D. PellegriniJr.; Optimal Timing of Preoperative Radiation for Prophylaxis Against Heterotopic OssificationA Rabbit Hip Model. The Journal of Bone & Joint Surgery. 2005 Feb;87(2):366-373.

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