Osteoporosis in elderly women; Bone traits, fracture and the PTH gene complex
Abstract: Background: Fragility fractures are a major health problem world wide and the numbers are growing due to ageing populations. Early identification of individuals at risk for osteoporosis and fracture, enabling preventive measures and treatment is essential. Bone strength is partly dependent on lifestyle but genetic factors account for approximately 70-80%. Parathyroid hormone (PTH) is the key regulator of calcium homeostasis in the human organism and in addition a powerful skeletal anabolic agent when administered as a drug. Dual energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD) in the hip and lumbar spine. However, at the lumbar spine in the elderly, degenerative changes frequently cause a falsely elevated BMD. Aims: To evaluate a hypothesized relationship between variation in PTH pathway genes, BMD, fracture, degenerative changes and bone geometry in elderly women. To evaluate the prevalence and localization of degenerative changes at the lumbar spine in elderly women and its impact on DXA measurements. Methods: 1044 women of the Osteoporosis Prospective Risk Assessment Study (OPRA) all 75 years at inclusion were measured by DXA at baseline, 5 and 10 years follow-up. Retrospective and prospective fractures were registered, a questionnaire regarding life style factors was answered and blood samples were obtained for genetic analysis. All lumbar DXA scan images were visually assessed regarding degenerative and other manifestations. Results: Association analysis showed a significant relationship between PTH haplotypes and fracture but not BMD. There were also a significant correlation between PTH haplotypes and hip strength analysis (HSA) parameters. PTH receptor 2 gene was related to prevalence of lumbar degenerative changes. The prevalence of lumbar degenerative changes (L1-L4) was high at baseline (43%) and significantly increasing over time (67% at 5 and 80% at 10 years follow-up). Vertebrae affected with degenerative changes had significantly higher BMD and there was a gradient over L1 to L4 with higher prevalence distally. Conclusions: Our results indicate that genetic variation within the PTH pathway genes are associated with fracture prevalence and hip strength indices based on skeletal geometry and degenerative changes but not with BMD in elderly women. We can furthermore conclude that if lumbar degenerative changes are taken into consideration when interpreting DXA scans diagnosis of osteoporosis can be more precise. We suggest the use of L1-L2 in elderly women to avoid under-diagnosis and misinterpretation of drug effect.
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