Osteoporotic fracture: muscular determinants and transition to consequences

Abstract

Osteoporosis is a metabolic disease characterised by reduced bone strength and deteriorated bone structure, which lead to an increased risk of fracture. Previous studies have focused on bone related risk factors but little attention on muscle strength and muscle mass. The present thesis reported a series of studies aimed at: determining the association between muscle strength and the risk of osteoporotic fracture and post-fracture mortality; developing a predictive model to predict the transition to deteriorated stages of bone health, i.e. fracture, recurrent fracture and post-fracture mortality; and determining the role of volumetric bone mineral density in gender-specific risk of osteoporotic fractures. Using data from Dubbo Osteoporosis Epidemiology, a 27-year prospective population-base study, I have shown that low quadriceps strength was a risk factor for osteoporotic fracture (except for fractures at head, toes and fingers) and the association was independent of bone mineral density (BMD) and history of falls. Moreover, low quadriceps strength was a significant risk factor for mortality following an osteoporotic fracture in both men and women. The association was independent of co-morbidities, BMD and history of falls. Probability and time of transition to fracture, re-fracture and post-fracture mortality were individually predicted by a multiple state Markov model. Men and women with high risk profile had higher risk and shorter time of transition from no fracture to fracture, recurrent fracture and death. The risk of osteoporotic fracture at the same value of estimated volumetric BMD was higher in women than in men. This work contributes to our understanding of the heterogeneity of consequences of osteoporosis by determining the negative association of low skeletal muscle strength and these outcomes. Furthermore, for the first time, predictive model for osteoporotic fracture is extended to assess the risk of its associated outcomes, including recurrent fracture and to post-fracture mortality. This work advances our knowledge on the gender difference in fracture risk. Ultimately, the current work will aid in prevention, treatment, and management of osteoporosis.