Chemotherapy Curtails Bone Formation From Compliant Compression Fixation of Distal Femoral Endoprostheses.

Background: Modulated compliant compressive forces may contribute to durable fixation of implant stems in patients with cancer who undergo endoprosthetic reconstruction after tumor resection. Chemotherapy effects on bone hypertrophy and osteointegration have rarely been studied, and no accepted radiologic method exists to evaluate compression-associated hypertrophy.
Questions/purposes: (1) What was the effect of chemotherapy on the newly formed bone geometry (area) at 1 year and the presumed osteointegration? (2) What clinical factors were associated with the degree of hypertrophy? (3) Did the amount of bone formation correlate with implant fixation durability? (4) Was the amount of new bone generation or chemotherapy administration correlated with Musculoskeletal Tumor Society (MSTS) score?
Methods: Between 1999 and 2013, we performed 245 distal femoral reconstructions for primary or revision oncologic indications. We evaluated 105 patients who received this implant. Ten were excluded because they lacked 2 years of followup and two were lost to followup, leaving 93 patients for review. All underwent distal femur reconstruction with the compliant compressive fixation prosthesis; 49 received postoperative chemotherapy and 44 did not. During this period, the implant was used for oncology patients < 60 years of age without metastases and with > 8 cm of intact, nonirradiated bone distal to the lesser trochanter and ≥ 2.5 mm of cortex. Our cohort included patients with painful loosening of cemented or uncemented stemmed femoral megaprostheses when revision with the compliant compressive device was feasible. Patients with high-grade sarcomas all received chemotherapy, per active Children's Oncology Group protocols, for their tumor diagnosis. At each imaging time point (3, 6, 9, 12, 18, 24 months), we measured the radiographic area of the bone under compression using National Institutes of Health open-access software, any shortening of the spindle-anchor plug segment distance as reflected by the exposed traction bar length, and prosthesis survivorship. Clinical and functional status and MSTS scores were recorded at each followup visit. Duration of prosthesis retention without aseptic loosening or mechanical failure was evaluated using Kaplan-Meier analysis, censoring patients at last followup.
Results: Chemotherapy was associated with the amount of overall bone formation in a time-dependent fashion. In the 12 months after surgery there was more bone formation in patients who did not receive postoperative chemotherapy than those who did (60.2 mm, confidence interval [CI] 49.3-71.1 versus 39.1, CI 33.3-44.9; p = 0.001). Chemotherapy was not associated with prosthesis survival. Ten-year implant survival was 85% with chemotherapy and 88% without chemotherapy (p = 0.74). With the number of patients we had, we did not identify any clinical factors that were associated with the amount (area) of hypertrophy. The hypertrophied area was not associated with the durability of implant fixation. MSTS scores were lower in patients treated with chemotherapy (25 versus 28; p = 0.023), but were not correlated with new bone formation.
Conclusions: The relationships among chemotherapy, bone formation, and prosthetic survivorship are complex. Because bone formation is less in the first year when the patient is being treated with chemotherapy, it is not clear if the rehabilitation schedule should be different for those patients receiving chemotherapy compared with those who do not. The relationship between early bone formation and the timing of weightbearing rehabilitation should be evaluated in a multicenter study.
Level of Evidence: Level III, therapeutic study.