To study the time course of demineralization and fracture incidence after spinal cord injury (SCI), 100 paraplegic men with complete motor loss were investigated in a cross-sectional study 3 months to 30 years after their traumatic SCI. Fracture history was assessed and verified using patients' files and X-rays. BMD of the lumbar spine (LS), femoral neck (FN), distal forearm (ultradistal part = UDR, 1/3 distal part = 1/3R), distal tibial diaphysis (TDIA), and distal tibial epiphysis (TEPI) was measured using DXA. Stiffness of the calcaneus (QUI.CALC), speed of sound of the tibia (SOS.TIB), and amplitude-dependent SOS across the proximal phalanges (adSOS.PHAL) were measured using QUS. Z-Scores of BMD and quantitative ultrasound (QUS) were plotted against time-since-injury and compared among four groups of paraplegics stratified according to time-since-injury (<1 year, stratum I; 1-9 years, stratum II; 10-19 years, stratum III; 20-29 years, stratum IV). Biochemical markers of bone turnover (deoxypyridinoline/creatinine (D-pyr/Cr), osteocalcin, alkaline phosphatase) and the main parameters of calcium phosphate metabolism were measured. Fifteen out of 98 paraplegics had sustained a total of 39 fragility fractures within 1,010 years of observation. All recorded fractures were fractures of the lower limbs, mean time to first fracture being 8.9 +/- 1.4 years. Fracture incidence increased with time-after-SCI, from 1% in the first 12 months to 4.6%/year in paraplegics since >20 years ( p<.01). The overall fracture incidence was 2.2%/year. Compared with nonfractured paraplegics, those with a fracture history had been injured for a longer time ( p<.01). Furthermore, they had lower Z-scores at FN, TEPI, and TDIA ( p<.01 to <.0001), the largest difference being observed at TDIA, compared with the nonfractured. At the lower limbs, BMD decreased with time at all sites ( r=.49 to.78, all p<.0001). At FN and TEPI, bone loss followed a log curve which leveled off between 1 to 3 years after injury. In contrast, Z-scores of TDIA continuously decreased even beyond 10 years after injury. LS BMD Z-score increased with time-since-SCI ( p<.05). Similarly to DXA, QUS allowed differentiation of early and rapid trabecular bone loss (QUI.CALC) vs slow and continuous cortical bone loss (SOS.TIB). Biochemical markers reflected a disproportion between highly elevated bone resorption and almost normal bone formation early after injury. Turnover declined following a log curve with time-after-SCI, however, D-pyr/Cr remained elevated in 30% of paraplegics injured >10 years. In paraplegic men early (trabecular) and persistent (cortical) bone loss occurs at the lower limbs and leads to an increasing fracture incidence with time-after-SCI.