High Serum Insulin-Like Growth Factor-Binding Protein 1 (IGFBP-1) is Associated with High Fracture Risk Independent of Insulin-Like Growth Factor 1 (IGF-I).

High serum levels of IGFBP-1 are related both to low body mass index (BMI) and to low insulin-like growth factor 1 (IGF-I), which both in turn are related to low bone mineral density (BMD) and to increased fracture risk. However, we have found no previous prospective studies on IGFBP-1 and fracture risk. Despite its name, IGFBP-1 is not only just a binding protein but also has its own IGF-independent effects, e.g., stimulating osteoclast differentiation. IGFBP-1 might have an IGF-related and/or an IGF-independent association to fracture risk. This is a population-based prospective cohort study with a ten-year follow-up of 351 women aged 69-79 at inclusion. Fracture and mortality data were collected from national health care registers. IGFBP-1 had a positive linear relation to the risk of both hip fractures and "major osteoporotic fractures" including fractures of the hip, spine, shoulder, and wrist. The age-adjusted hazard ratio (HR) for a hip fracture was 1.46 (95 % CI 1.08-1.99) for one SD increase in IGFBP-1. The corresponding age-adjusted HR for major osteoporotic fractures was 1.33 (95 % CI 1.05-1.69). The relation between IGFBP-1 and fracture risk was not confounded by either IGF-I or BMI. Femoral neck BMD, however, mediated 56 % of the total "effect" of IGFBP-1 on hip fracture risk. In conclusion, IGFBP-1 had a positive linear relation to fracture risk, partly mediated by BMD but not related to IGF-I or BMD. This implies that IGFBP-1 might be an important factor in bone turnover and that further studies on this would be valuable.