• Basic Science

The human skeleton optimizes its microarchitecture by elaborate adaptations to mechanical loading during development and growth. The mechanisms for adaptation involve a multistep process of cellular mechanotransduction stimulating bone modelling, and remodeling resulting in either bone formation or resorption. This process causes appropriate microarchitectural changes tending to adjust and improve the bone structure to its prevailing mechanical environment. Normal individual reaches peak bone mass at age between 25 and 30 years, and thereafter bone mass declines with age in both genders. The bone loss is accompanied by microarchitectural deterioration resulting in reduced mechanical strength likely leading to fragility fractures. With aging, inevitable bone loss occurs, which is frequently the cause of osteoporosis; and inevitable bone and joint degeneration happens, which often results in osteoarthrosis. These diseases are among the major health care problems in terms of socio-economic costs. The overall goals of the current series of studies were to investigate the age-related and osteoarthrosis (OA) related changes in the 3-D microarchitectural properties, mechanical properties, collagen and mineral quality of subchondral cancellous and cortical bone tissues. The studies included mainly two parts. For human subjects: aging- (I–IV) and early OArelated (V–VI) changes in cancellous bone properties were assessed. For OA guinea pig models (VII–IX), three topics were studied: firstly, the spontaneous, age-related development of guinea pig OA; secondly, the potential effects of hyaluronan on OA subchondral bone tissues; and thirdly, the effects on OA progression of an increase in subchondral bone density by inhibition of bone remodeling with a bisphosphonate. These investigations aimed to obtain more insight into the age-related and OA-related subchondral bone adaptations. Microarchitectural adaptation in human aging cancellous bone The precision of micro-CT measurement is excellent. Accurate 3-D micro-CT image datasets can be generated by applying an appropriate segmentation threshold. A fixed threshold may be used to obtain reliable volume fraction data, and this fixed threshold may be determined from the Archimedes based volume fraction of a subgroup of specimens (I). Based on accurately generated micro-CT datasets, age related microarchitectural changes of human tibial cancellous bone have been demonstrated (II, III). Apart from connectivity, all measured microarchitectural properties correlate significantly with age. However, age-related changes in the properties of human tibial cancellous bone do not follow the same pattern, nor do they occur at the same age. The observed increase of anisotropy and the constant nature of connectivity suggest an important bone remodeling mechanism that normal aging tibia may adapt trabecular volume orientation. Namely, that the aging trabeculae align preferentially to the primary loading direction to compensate bone loss (III). Age-related changes in trabecular thickness and structure type become significant first after 80 years of age. The plate-like structure reflects high mechanical stress whereas rod-like structure reflects low mechanical stress (II). Trabecular structure type and bone volume fraction correlates strongly. Trabecular structure type together with anisotropy correlates well with the Young’s modulus. The most effective microarchitectural properties for predicting the mechanical properties of cancellous bone seem to differ with age (IV). Microarchitectural adaptation in human osteoarthritic subchondral bone In early human OA subchondral cancellous bone, none of the mechanical properties of cancellous bone can be predicted by the measured physical/compositional properties (V). The increased trabecular thickness and density, but relatively decreased connectivity suggests a mechanism of bone remodeling in early OA as a process of filling trabecular cavities. This process leads to a progressive change of trabeculae from rod-like to plate-like, the opposite to that of normal ageing. The increase in bone tissue accompanied with deteriorated microarchitecture in early-stage OA cancellous bone does not account for the loss of mechanical properties, which suggests deterioration in the quality of OA cancellous bone (VI). Microarchitectural adaptation in guinea pig osteoarthritic subchondral bone Age-related pronounced changes of the microarchitecture and bone matrix composition of the subchondral bone tissues in guinea pig have been demonstrated. These changes do not appear to follow the same pattern as in normal aging and may have different influences on the resulting mechanical properties (VII). Intra-articular injection of hyaluronan effectively protects against cartilage degeneration in guinea pig primary OA. The decrease of subchondral bone density and thickness and change of trabecular structure toward rod-like result in more compliant subchondral bone and thereby reduces cartilage stress during impact loading. Moreover, hyaluronan maintains the mechanical properties of cancellous bone likely through increasing its mineralization. Early administration of hyaluronan is effective for intervention of OA initiation and progression, and short-term early HA treatment is sufficient to maintain treatment effects in OA guinea pig model (VIII). The inhibition of bone remodeling by ALN leads to significant increase of subchondral bone mass and bone mineral content, and marked changes of microarchitecture. Furthermore, the resulting increased bone mass accelerates articular cartilage degeneration at the medial condyle and, to some extent, at the lateral condyle. These results suggest that increased subchondral bone density promotes OA progression and call for circumspection in using bone density–enhancing drugs for intervention of primary OA (IX). Conclusion Age-related musculoskeletal diseases increase as a result of increase in the elderly population and a change in lifestyle. Over the last a few decades, much significant research on the properties has been carried out on diseases such as age-related bone fracture, prosthetic loosening, bone remodeling, and degenerative bone diseases on both axial central vertebra and peripheral trabecular bone. We have now achieved a great deal of knowledge on normal aging- and diseases-related changes in bone properties and quality. This knowledge is of major importance for the understanding of degenerative bone diseases, and for the design, fixation, survival of joint prosthesis, functional adaptation of host bone; and for application of biomaterials regarding interface reaction, fracture repair and defect healing. Understanding the microarchitectural properties, mechanical adaptations, and collagen and mineral qualities of subchondral bone tissues highlighted in these studies may help to gain more insights into the pathogenesis of degenerative bone diseases and to target and develop novel approaches for the intervention and treatment. Key words: Three-dimensional reconstruction; microarchitectural properties; microarchitectural adaptation; micro-CT; mechanical properties; collagen; mineral; aging; osteoarthrosis; osteoporosis; rheumatoid arthritis; subchondral bone tissues; bone quality; human; guinea pig

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