Zickel, Robert E. M.D.; Aaron, Alan D. M.D.

Journal of Bone & Joint Surgery - American Volume:


    In the article “Current Concepts Review. Treatment of Metastatic Adenocarcinoma of the Pelvis and the Extremities” (79-A: 917–932, June 1997), Aaron indicated that the ideal treatment for fractures secondary to metastases is internal fixation or prosthetic replacement with methylmethacrylate. Aaron cited an article by Harrington et al.3, published in 1976, that advocated the use of methylmethacrylate with internal fixation. It was also stated that the duration of survival increased from 11.6 to 246 months. (I am sure that a decimal point was omitted and that this should be 24.6 months.) This improvement was attributed to the patients being able to walk again, which was thought to be secondary to the use of methylmethacrylate. However, Aaron cited the work of other investigators2,6 who also used methylmethacrylate in addition to internal fixation or prosthetic replacement but reported much shorter durations of survival. In particular, Lane et al.6 reported a duration of survival of only 5.6 months. It seems that the duration reported by Harrington et al. may have been affected by other factors, such as the natural history of the disease, the type and location of the tumor, and so on.

    Aaron cited articles by Mickelson and Bonfiglio7 as well as by Mouradian and me13 in which the Zickel subtrochanteric device was used without methylmethacrylate. Aaron noted that shortening was associated with use of this device, but he did not mention that the clinical outcomes were very good in both of those articles. There was some shortening, but it did not affect the end result of the procedure, the goals of which were mobilization and relief of pain. Those articles made two important points: first, the patients were mobilized quickly and, second, there was a substantial rate of fracture-healing in the patients who survived.

    My main objections to the endorsement of routine use of methylmethacrylate to treat pathological fractures are that it complicates the operation and it has been shown to deter fracture-healing. It should be noted that Fracchia and I12 reported on a later series of seventy-seven cases to the Hip Society in 1986. We again found an increase in the prevalence of fracture-healing, even though methylmethacrylate was used in only one of those fractures. Enis et al.1, in a study of dogs, reported that six of eight fractures that were fixed internally with plates and methylmethacrylate went on to non-union because of the interposition of methylmethacrylate at the fracture site.

    In short, while methylmethacrylate can be helpful in the treatment of some pathological fractures or lesions, I do not think that it should be used routinely as most bone metastases to the femur are from carcinoma of the breast and are usually radiosensitive with a good chance of bone-healing.

    Robert E. Zickel, M.D.: Department of Orthopaedic Surgery, New York Medical College, Valhalla, New York 10595

    Dr. Aaron replies:

    I thank Dr. Zickel for bringing the typographical error to my attention. He is correct that the duration of survival increased from 11.6 to 24.6 months.

    I concur that the duration of survival of patients who have metastatic bone disease depends on several factors. The type of tumor is clearly important, as the average five-year rate of survival of patients who have breast cancer (82 per cent) is much greater than that of patients who have lung cancer (14 per cent)10. Even if an investigator groups patients according to the specific type of tumor (such as breast cancer), however, large differences in survival are apparent depending on the pattern and extent of metastases. Koenders et al.5 reported that the duration of survival of patients who had metastases from breast cancer was thirty-four months when the metastases were to bone, forty-one months when they were to soft tissue, and sixteen months when they were to visceral organs. The decade in which the investigation was performed may also play a role in large retrospective series, as there are large variations in patient survival depending on the year of presentation. For example, the five-year survival rate10 for women diagnosed with breast cancer in 1963 was 63 per cent compared with 82 per cent for women diagnosed in 1990. Most of the studies focusing on the treatment of metastatic bone disease have not been standardized with respect to the type of tumor, and the authors have not reported the presence of concomitant visceral organ metastases and may have drawn from a retrospective pool of patients over a period of several years. Given these discrepancies, it is not surprising that there are differences in the duration of patient survival. The more important message is that the early mobilization of patients can improve survival.

    Dr. Zickel brings up several points relating to the routine use of methylmethacrylate in conjunction with internal fixation. He and Mouradian13 reported good clinical outcomes in their study, which was published in 1976. The patients were separated into three main groups. Group IA included seven patients who had a pathological fracture and an unknown primary carcinoma, group IB included twenty-eight patients who had a pathological fracture and a known primary carcinoma, and group II included eleven patients who had an impending pathological fracture. Walking ability was classified as either able to transfer from bed to chair or able to walk. Only one of the seven patients in group IA, eighteen of the twenty-eight patients in group IB, and ten of the eleven patients in group II were able to walk at the time of presentation. Therefore, only twenty-nine (63 per cent) of the forty-six patients were able to walk when they were treated with internal fixation without methylmethacrylate. Loss of fixation was also reported; three patients had loosening of the nail within the femoral neck, and one of these patients needed a reoperation. Yazawa et al.11 reported that, in a large series of patients, the highest rate of failure of the implant (23 per cent) occurred in association with proximal femoral lesions that had been treated with a screw and a side-plate. Yazawa et al. strongly suggested the use of methylmethacrylate even when intramedullary devices were used.

    The effect of methylmethacrylate on the healing of pathological fractures is indeed a concern. However, although healing is a goal of internal fixation of pathological fractures, it is rarely achieved. Zickel and Mouradian13 reported that union was achieved in only thirteen of the thirty-five patients in groups IA and IB; eighteen died before union occurred, and four were lost to follow-up. As I discussed in my review, pain relief and mobility are the primary goals of operative treatment.

    The adverse effect of methylmethacrylate on fracture-healing is a concern in patients who have a longer life expectancy. However, the mere presence of methylmethacrylate at a fracture site does not necessarily signal an impending non-union. Hubbard4 studied ninety rabbits that had had osteotomy of the femoral shaft followed by fixation with an intramedullary nail. The rabbits were divided into three groups: group 1 was a control group, group 2 had intramedullary methylmethacrylate cement added, and group 3 had an external collar of methylmethacrylate added to the osteotomy site. The osteotomies in groups 1 and 2 healed while none of those in group 3 did. Reikeras8 found that the presence of intramedullary methylmethacrylate did not impair fracture-healing in rats at forty, sixty, and ninety days after the operation. The torsional moment, the elastic stiffness, and the volume and density of the callus did not differ between the rats who had intramedullary methylmethacrylate and those in the control group. Also, Straw et al.9 reported that the presence of methylmethacrylate in intercalary allografts in a canine model did not adversely affect the rate of union of the allograft with the host bone.

    I do not condone the overzealous use of methylmethacrylate. However, it is clear that, when it is used judiciously, augmentation of internal fixation devices with methylmethacrylate can improve fixation.

    More importantly, most studies of the operative treatment of metastatic bone disease fail to answer these and other questions adequately. It is conceivable that the need to augment intramedullary devices with methylmethacrylate may be lessened in light of the increased availability of acceptable locking-nail devices for reconstruction after proximal femoral fractures. Possibly, newer adjuvants for fracture fixation, such as the injectable ceramic polymer Dahlite, will reduce the risk of non-union and replace methylmethacrylate. Better prospective studies are necessary before these and other questions can be answered satisfactorily.

    Alan D. Aaron, M.D.: Chevy Chase Building, Suite 604, 5530 Wisconsin Avenue, Chevy Chase, Maryland 20815-4470

    1. Enis, J. E.; McCollough, N. C., III; and Cooper, J. S.: Effects of methylmethacrylate in osteosynthesis. Clin. Orthop., 105: 283-294, 1974.
    2. Habermann, E. T.; Sachs, R.; Stern, R. E.; Hirsh, D. M.; and Anderson, W. J., Jr.: The pathology and treatment of metastatic disease of the femur. Clin. Orthop., 169: 70-82, 1982.
    3. Harrington, K. D.; Sim, F. U.; Enis, J. E.; Johnston, J. O.; Dick, H. M.; and Gristina, A. G.: Methylmethacrylate as an adjunct in internal fixation of pathologic fractures. Experience with three hundred and seventy-five cases. J. Bone and Joint Surg., 58-A: 1047-1055, Dec. 1976.
    4. Hubbard, M. J.: The effect of acrylic cement on the union of internally fixed experimental fractures of the femoral shaft in the rabbit. Injury, 11: 325-330, 1980.
    5. Koenders, P. G.; Beex, L. V.; Kloppenborg, P. W.; Smals, A. G.; and Benraad, T. J.: Human breast cancer: survival from first metastasis. Breast Cancer Study Group. Breast Cancer Res. and Treat., 21: 173-180, 1992.
    6. Lane, J. M.; Sculco, T. P.; and Zolan, S.: Treatment of pathological fractures of the hip by endoprosthetic replacement. J. Bone and Joint Surg., 62-A: 954-959, Sept. 1980.
    7. Mickelson, M. R., and Bonfiglio, M.: Pathological fractures in the proximal part of the femur treated by Zickel-nail fixation. J. Bone and Joint Surg., 58-A: 1067-1070, Dec. 1976.
    8. Reikeras, O.: Mechanical effects of intramedullary acrylic cement on fracture healing in rats. Acta Orthop. Scandinavica, 55: 339-341, 1984.
    9. Straw, R. C.; Powers, B. E.; Withrow, S. J.; Cooper, M. F.; and Turner, A. S.: The effect of intramedullary polymethylmethacrylate on healing of intercalary cortical allografts in a canine model. J. Orthop. Res., 10: 434-439, 1992.
    10. Wingo, P. A.; Tong, T.; and Bolden, S.: Cancer statistics, 1995. CA: Cancer J. Clinicians, 45: 8-30, 1995.
    11. Yazawa, Y.; Frassica, F. J.; Chao, E. Y. S.; Pritchard, D. J.; Sim, F. H.; and Shives, T. C.: Metastatic bone disease. A study of the surgical treatment of 166 pathologic humeral and femoral fractures. Clin. Orthop., 251: 213-219, 1990.
    12. Zickel, R. E., and Fracchia, M. J.: Management of metastatic tumors of the proximal femur: a continuing study. In The Hip. Proceedings of the Fourteenth Open Scientific Meeting of The Hip Society, pp. 207-212. St. Louis, C. V. Mosby, 1987.
    13. Zickel, R. E., and Mouradian, W. H.: Intramedullary fixation of pathological fractures and lesions of the subtrochanteric region of the femur. J. Bone and Joint Surg., 58-A: 1061-1066, Dec. 1976.
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