Genetic factors have been implicated in the pathogenesis of osteoporosis, which is a common disorder in primary biliary cirrhosis (PBC). Insulin-like growth factor I (IGF-I) gene microsatellite repeat polymorphism was found to be associated with osteoporosis in some studies and collagen type I alpha 1 (COLIA1) SP1 "s" allele was associated with lower bone mineral density (BMD) in PBC. IGF-I treatment restored osteopenia and reduced fibrogenesis in experimental cirrhosis. We investigated IGF-I and COLIA1 gene polymorphisms and BMD in Hungarian PBC patients. METHODS 70 female patients with PBC were enrolled (mean age: 57.6 yrs, range: 37-76 yrs, each AMA M2 positive, stage II-IV). 139 age-matched female subjects served as controls (mean age: 55.9 yrs, range: 43-72 yrs). COLIA1 and IGF-I microsatellite repeat polymorphisms were determined by PCR. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (Lunar, Prodigy, WI, USA) in lumbar spine (LS) and femoral neck (FN). RESULTS The IGF-I polymorphism was not different between PBC patients (192/192 = 34.2%, 194/192 = 28.6%, other = 37.2%) and controls (192/192 = 38.2%, 194/192 = 30.9%, other = 30.9%). The genotype frequency of COLIA1 polymorphism was also not different between PBC patients (SS = 72.9%, Ss = 22.8% and ss = 4.3%) and controls (SS = 58.4%, Ss = 35.9% and ss = 5.7%), however the "s" allele was significantly less frequent in patients with PBC (p = 0.038). Osteoporosis was present in 22 patients (31.4%). The IGF-I 192/192 allele was associated with higher FN Z-score compared to other genotypes (p = 0.036). CONCLUSIONS In contrast to previous studies the "s" allele was less frequent in patients with PBC, and its presence was not associated with lower bone mineral density. Since IGF-I polymorphism was associated to BMD, it may be hypothesized that IGF-I microsatellite repeat polymorphism together with other genetic and environmental factors may be involved in the complex regulation of BMD in PBC.