Spinal cord injury (SCI) leads to severe bone loss in the paralysed limbs and to a resulting increased fracture risk thereof. Since long bone fractures can lead to comorbidities and a reduction in quality of life, it is important to improve bone strength in people with chronic SCI. In this prospective longitudinal cohort study, we investigated whether functional electrical stimulation (FES) induced high-volume cycle training can partially reverse the loss of bone substance in the legs after chronic complete SCI. Eleven participants with motor-sensory complete SCI (mean age 41.9 +/- 7.5 years; 11.0 +/- 7.1 years post injury) were recruited. After an initial phase of 14 7 weeks of FES muscle conditioning, participants performed on average 3.7 +/- 0.6 FES-cycling sessions per week, of 58 +/- 5 min each, over 12 months at each individual's highest power output. Bone and muscle parameters were investigated in the legs by means of peripheral quantitative computed tomography before the muscle conditioning (t(1)), and after six (t(2)) and 12 months (t(3)) of high-volume FES-cycle training. After 12 months of FES-cycling, trabecular and total bone mineral density (BMD) as well as total cross-sectional area in the distal femoral epiphysis increased significantly by 14.4 +/- 21.1%, 7.0 +/- 10.8% and 1.2 +/- 1.5%, respectively. Bone parameters in the femoral shaft showed small but significant decreases, with a reduction of 0.4 +/- 0.4% in cortical BMD, 1.8 +/- 3.0% in bone mineral content, and 1.5 +/- 2.1% in cortical thickness. These decreases mainly occurred between t(1) and t(2). No significant changes were found in any of the measured bone parameters in the tibia. Muscle CSA at the thigh increased significantly by 35.5 +/- 18.3%, while fat CSA at the shank decreased by 16.7 +/- 12.3%. Our results indicate that high-volume FES-cycle training leads to site-specific skeletal changes in the paralysed limbs, with an increase in bone parameters at the actively loaded distal femur but not the passively loaded tibia. Thus, we conclude that high-volume FES-induced cycle training has clinical relevance as it can partially reverse bone loss and thus may reduce fracture risk at this fracture prone site.