Distal Lower Limb Bone Pain After Renal Transplantation

In the August 15, 1995 issue, Stevens et al. (1) report the occurrence in four kidney graft recipients of a syndrome of lower limb bone pain involving mainly knees and ankles that was distinct from avascular bone necrosis. Pain was aggravated by weightbearing and eased by rest. It resolved spontaneously within 6-13 months. X-rays of the symptomatic areas were unremarkable while technetium bone scans showed increased uptake of the tracer in the painful joints. The authors are unable to explain the mechanism of pain but suspect a toxic effect of cyclosporine on bone. They are clearly unaware of the fact that we reported, 2 years ago, on a virtually identical syndrome in nine kidney graft recipients: we thoroughly described its clinical presentation and outcome, as well as its characteristics on conventional radiographs, bone scan, and mainly magnetic resonance imaging (2, 3). We concluded that this syndrome results from epiphyseal impaction and suggested that cyclosporine was not the only etiological factor (2, 3). Briefly, 9 out of 86 patients transplanted over a 2-year period (4 men, 5 women; mean age, 40 years; range, 32-59) experienced unexplained severe spontaneous osteoarticular pain of lower limbs 19-105 (mean 58) days after renal transplantation. Pain involved 27 joints, mainly the ankles and knees. Clinical examination was usually unremarkable. Favorable outcome was the rule; mean duration of pain was 86 days (range, 19-175). Standard radiographs were abnormal in 11/27 affected joints (41%). Patchy osteoporosis of the epiphyseal cancellous bone was visible in eight symptomatic joints. Its extent and severity were quite variable. Joint spaces were preserved. Effusions were detected within three joints. Metaphyseal periosteal reactions were also noted in three cases. Bone scan disclosed a total of 54 foci of increased uptake in 22 out of 27 affected joints (81%). Patterns of involvement varied from localized (1-4/joint) foci to a more diffuse uptake in the whole joint. MR imaging was obtained in 23 symptomatic joints (eight patients). In 19 of them (83%), the epiphyseal bone marrow contained one or several ill-defined foci of low intensity signal on T1-weighted images with corresponding high intensity on T2-weighted images. These foci were predominantly localized in subchondral bone areas. Several contained bands of lower intensity on both T1- and T2-weighted images. Among joints re-examined 9-12 months after resolution of the symptoms, x-rays showed periosteal reactions in 31%, and bone scan disclosed persistent increased uptake in 53%, whereas epiphyseal MR abnormalities had completely disappeared in 86% of the joints. We proposed that this syndrome resulted from epiphyseal impaction. This hypothesis fits with the clinical presentation and the spontaneously favorable evolution. It is supported mainly by the MR findings. The presence of ill-defined focal areas of low-signal intensity on T1-weighted images which become brighter on T2-weighted pictures is consistent with edema, and/or hemorrhages within the bone medullary spaces. Identical abnormalities have been reported in cases of stress fractures (4-6), insufficiency fractures (5), and in radiographically occult posttraumatic lesions of the knees (7, 8). Moreover, the presence, within these areas, of linear bands of low-signal intensity on both T1- and T2-weighted images is consistent with an impaction within cancellous bone (7-10). The complete long-term resolution of the MR abnormalities is also consistent with occult fractures (5-7). The increased uptake of the radiotracer in the corresponding areas of MR abnormalities, although nonspecific, is also compatible with impactions (6, 7) as it reflects an augmented blood flow and/or an increased osteoblastic activity in the damaged area (11, 12); the slow resolution of the scintigraphic abnormalities is probably related to the duration of the bone remodeling process (12). Although nonspecific and very subtle, the x-ray findings of subchondral bone rarefactions and subsequent periosteal reactions are also compatible with the development and repair of epiphyseal impactions (13). As suggested by Stevens et al. and several other authors, cyclosporine could be a risk factor for this syndrome for the reasons developed in Stevens et al.'s article. However, it cannot be the only etiological factor, since an identical symptomatology has been described in kidney recipients who were not given cyclosporine (14-16). Furthermore, symptoms subsided in our patients despite the maintenance of a virtually unchanged cyclosporine dosage. Additional factor(s), such as excessive physical activities in the early posttransplant period, must therefore play a role. Eric Goffin1; Y. Pirson; B. Vande Berg; C. van Ypersele de Strihou Department of Nephrology; Hôpital Saint Luc; Brussels, Belgium