Female premenopausal fracture risk is associated with gc phenotype.
The phenotype of the vitamin D binding and macrophage activating protein, Gc, is a predictor of premenopausal bone fracture risk, possibly mediated through activation of osteoclasts. This was concluded from a study on 595 Danish perimenopausal women 45-58 years of age (30,040 person years).


BACKGROUND
The multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, or vitamin D binding protein (DBP), has two functions with relation to bone tissue: it is the major carrier protein of vitamin D in the circulation, and deglycosylation converts it into a very potent macrophage- and osteoclast-activating factor (Gc-MAF). There are several phenotypes of Gc, and in this study, we examined the relation between Gc phenotype and bone fragility.


METHODS
By isoelectric focusing we identified the Gc phenotype of 595 white recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS) and identified three groups: Gc1-1 (n = 323), Gc1-2 (n = 230), and Gc2-2 (n = 42). Differences between the three groups were examined with respect to number of fractures before enrollment, BMC and BMD, and various biochemical and clinical parameters, including the concentration of Gc measured by immunonephelometry and the concentration of the macrophage marker soluble CD163 measured by ELISA.


CONCLUSIONS
The risk of having at least one premenopausal bone fracture (total number of women with fracture = 179) differed significantly (p = 0.017) in women with phenotype Gc1-1 (110/323 = 0.34), Gc1-2 (63/230 = 0.27), and Gc2-2 (6/42 = 0.14). The differences were even more striking (p = 0.005) for fractures caused by low-energy traumas. Using logistic regression, we found the relative risk of premenopausal fracture to be 0.32 (0.13-0.80) in Gc2-2 compared with Gc1-1. We propose that the Gc phenotypes cause differences in osteoclast activity, a theory supported by our finding of lower levels of Gc and of soluble CD163 in women with Gc2-2 compared with Gc1-1.
Lauridsen
Anna Lis
AL
Department of Clinical Biochemistry, AKH, Aarhus University Hospital, Aarhus C, Denmark. allau@akh.aaa.dk
Vestergaard
Peter
P
Hermann
Anne Pernille
AP
Moller
Holger Jon
HJ
Mosekilde
Leif
L
Nexo
Ebba
E
D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015519:Bone Density; D003718:Denmark; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D017697:Premenopause; D011956:Receptors, Cell Surface / Q000235:genetics; D012307:Risk Factors; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D014809:Vitamin D-Binding Protein