Bone Integrity for a Lifetime with Mechanical Loading

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Bone Integrity for a Lifetime through Mechanical Loading Over half a billion people worldwide are affected by musculoskeletal disorders which dramatically diminish functional independence. The next generation of technologies for the assessment, intervention and treatment for skeletal integrity will be specific to the individual and designed to optimise their outcomes. The long-term goal of the proposed research program is to provide a scientific basis for the maintenance of bone integrity over a person's lifetime by improving the understanding of bone mechanics and its adaptive response. The integration of emerging technologies, computer simulation, and tissue biology provide a unique approach to unlock the processes responsible for bone adaptation. Key features of bone integrity are composition, mineral density and fracture resistance, which are maintained through a balanced process of formation and resorption. Changes in micro-architecture, stiffness and strength in response to mechanical and biochemical stimuli are well documented. However, the metabolic pathways that change the mechanical and biochemical stimuli into a biological response are unclear. To understand this adaptive response, a unique ex vivo bone culture experiment has been designed, tested and validated. In this approach, explanted trabecular bone cores, perfused with culture medium, maintain viable tissue for up to 7 weeks. Ex vivo bone cores demonstrate increased bone mineral apposition under load and mimic in vivo human bone metabolism. This system provides a unique opportunity to investigate human bone adaption beyond the more common approach of 2D cell culture or more complex animal models. The short-term objectives are to quantify and simulate the response of trabecular bone cores and bone-implant systems to strain rate, load and hormones. A series of 3 experiments and simulations with live human trabecular bone will quantify the adaptive biological and morphological responses to controlled stimuli. This rich dataset will feed the development of algorithms to predict the response of bone and bone-implant systems to stimuli. Over a 5y period 11.25 HQP will be trained in bone biomechanics, bone culture and computer simulations. Fragility fracture in the aging population is a major public health concern. Projected increases of more than 200% in rates of osteoporotic hip fracture by 2050 are of concern due to associated rates of mortality (20-25%), loss of mobility (40%) and dependency (33%). It is well known that cyclic loading is a critical factor in bone formation; and therefore, can reduce rates of fragility fracture. However, it is not well understood, what form of cyclic load, e.g. the magnitude and strain rate, stimulates bone formation. The proposed research program provides the scientific basis and technology that can lead to new options to promote bone integrity and innovations in orthopaedic treatment.