• Hip and knee surgery
• Basic Science

The thesis is comprised by a review and 4 original papers – a cross-sectional study (published) a cross-sectional genetic association study, an in vitro experimental study, and a case-control study (drafts to be submitted). Risk factors for hip fracture (HF) include age, previous history of fracture and low body weight or body mass index. HF is, furthermore, one of the most serious consequences of osteoporosis. The purpose of the thesis was to investigate the potential use of measurements of the macroscopic geometry of the human proximal femur to predict the risk of HF. Moreover, we wanted to investigate the relative power of geometric parameters and bone mineral density (BMD) in that respect. Clinical studies have suggested that geometrical parameters of the hip such as femoral neck axis length (FNAL), neck-shaft angle (NSA), neck width (NW), and femoral head radius (HR) may predict the risk of HF independent of BMD. Few experimental data, however, have been published to support this. There is a significant genetic contribution to the risk of osteoporosis. Polymorphisms in a number of genes including those coding for the methylene-tetrahydrofolate reductase (MTHFR c.677C>T), the purinergic P2X7 receptor, and the low-density lipoprotein-receptor-related protein 5 (LRP5 exon 9 (c.266A>G)), have been associated with an increased fracture incidence and/or reduced bone mineral density (BMD). Hip geometry, however, is independently associated with risk of HF and studies in twins have suggested that hip geometry is genetically programmed. There are, however, discrepancies in the literature. Furthermore, no studies have described the natural variation in hip geometry in relation to Danish population characteristics. In a cross-sectional study, comprising 94 men and 155 women aged 19 to 79 years, we studied the normal variation in hip geometry. Our data confirmed that the macroscopic geometry of the human proximal femur differs between men and women and that FNAL, NW, and HR correlate with body height. Moreover, NW is associated with age in men but not in women. In a cross-sectional study, comprising 800 perimenopausal women aged 44 to 59 years, no significant association between four genetic polymorphisms (MTHFR c.677C>T genotype polymorphism, the P2X7 A1513C polymorphism, the P2X7 T1729A polymorphism, and the LRP5 exon 9 (266A/G) polymorphism) and hip geometry could be demonstrated. In a cross-sectional study comprising 38 bone specimens excised from recently diseased patients (age 37 to 55 years) during medico-legal autopsy, we found that the in vitro maximal strength of the proximal femur was predicted by BMD (R=0.49, p

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