Osteoporosis is a condition marked by low bone mineral density and the deterioration of bone tissue. One of the main clinical and economic consequences of osteoporosis is skeletal fractures. To assess the healthcare and work loss costs of US patients with non-vertebral (NV) osteoporotic fractures. Privately insured (aged 18-64 years) and Medicare (aged >/=65 years) patients with osteoporosis (ICD-9-CM code: 733.0x) were identified during 1999-2006 using two claims databases. Patients with an NV fracture (femur, pelvis, lower leg, upper arm, forearm, rib or hip) were matched randomly on age, sex, employment status and geographic region to controls with osteoporosis and no fractures. Patient characteristics and annual healthcare costs were assessed over the year following the index fracture for privately insured (n = 4764) and Medicare (n = 48 742) beneficiaries (Medicare drug costs were estimated using multivariable models). Indirect (i.e. work loss) costs were calculated for a subset of privately insured, employed patients with available disability data (n = 1148). All costs were reported in $US, year 2006 values. In Medicare, mean incremental healthcare costs per NV fracture patient were $US13 387 ($US22 466 vs $US9079; p < 0.05). The most expensive patients had index fractures of the hip, multiple sites and femur (incremental costs of $US25 519, $US20 137 and $US19 403, respectively). Patients with NV non-hip (NVNH) fractures had incremental healthcare costs of $US7868 per patient ($US16 704 vs $US8836; p < 0.05). Aggregate annual incremental healthcare costs of NVNH patients in the Medicare research sample (n = 35 933) were $US282.7 million compared with $US204.1 million for hip fracture patients (n = 7997). Among the privately insured, mean incremental healthcare costs per NV fracture patient were $US5961 ($US11 636 vs $US5675; p < 0.05). The most expensive patients had index fractures of the hip, multiple sites and pelvis (incremental costs of $US13 801, $US9642 and $US8164, respectively). Annual incremental healthcare costs per NVNH patient were $US5381 ($US11 090 vs $US5709; p < 0.05). Aggregate annual incremental healthcare costs of NVNH patients in the privately insured sample (n = 4478) were $US24.1 million compared with $US3.5 million for hip fracture patients (n = 255). Mean incremental work loss costs per NV fracture employee were $US1956 ($US4349 vs $US2393; p < 0.05). Among patients with available disability data, work loss accounted for 29.5% of total costs per NV fracture employee. The cost burden of NV fracture patients to payers is substantial. Although hip fracture patients were more costly per patient in both Medicare and privately insured samples, NVNH fracture patients still had substantial incremental costs. Because NVNH patients accounted for a larger proportion of the fracture population, they were associated with greater aggregate incremental healthcare costs than hip fracture patients.