title: 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).
abstract: 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.
authors.affiliation: Division of Family Medicine Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Alfred Nobels allé 12, Huddinge, 14183, Stockholm, Sweden. hans.lundin@ki.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Lundin
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Sääf
authors.affiliation: Division of Family Medicine Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Alfred Nobels allé 12, Huddinge, 14183, Stockholm, Sweden.
authors.forename: Lars-Erik
authors.initials: LE
authors.lastname: Strender
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Nyren
authors.affiliation: Division of Family Medicine Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Alfred Nobels allé 12, Huddinge, 14183, Stockholm, Sweden.
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Johansson
authors.affiliation: Division of Family Medicine Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Alfred Nobels allé 12, Huddinge, 14183, Stockholm, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Salminen
mesh_terms: D000368:Aged; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D015999:Multivariate Analysis; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000150:complications; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I
keywords: DXA; Fracture risk assessment; GH/IGF1; General population studies; Osteoblasts