The complex relationship between bone remodeling and the physical and material properties of bone.

Bone’s fracture resistance is dependent on the amount of bone, its architectural organization, and the material properties of the matrix that compose it. Although past concentration has been on mass and geometry, there is increasing recognition that bone’s material properties play a critical role in its fracture resistance. Unlike bone mass which is determined by one feature—how much?—or architecture, which is determined by two features—amount and location—material properties are determined by a dynamic complex and multi-level set of molecular components and processes that are interdependent. This includes the materials themselves—collagen, mineral, noncollagenous proteins, and water—how they are assembled, and the nature of the interfaces between them. These properties of the material are, in turn, partly dependent on the rate of bone turnover. As turnover decreases, bone’s mean tissue age becomes older, causing the collagen to become more highly cross-linked, the mineral to accumulate and contribute to increasing homogeneity, and the tissue to become less hydrated (only partly because mineral displaces some of the water). During aging, each of these features contributes to decrease the ductility of the bone, which in turn contributes to the skeletal fragility caused by bone loss and measured by BMD. The recent paper in Osteoporosis International by Ural et al. [1] examines age-dependent and age-independent correlations among several parameters of cortical bone measured from the same donors and that define bone quality at the tissue level. The paper shows the effects that age-related changes in bone remodeling parameters have on properties of the tissue that help to define bone quality. The paper shows that fewer sites of resorption and smaller resorption pits are associated with more areas of diffuse microdamage, but no relationship to linear microcrack density, independent of age. These relationships are all shown through correlation analysis, which doesn’t define causation and may reflect different effects stemming from a single cause. For example, the data show that the resorption pit density (a surrogate for activation frequency) and area of diffuse damage in bone are inversely related, yet recent evidence suggests that diffuse damage does not target itself for repair like linear microcracks do. Herman et al. [2] first showed that although areas associatedwith linear microcracks cause osteocyte apoptosis and increase activation of new remodeling units, those areas of bone that contain only diffuse damage have neither elevated osteocyte apoptosis nor altered activation and repair. This year, Seref-Felenguez et al. [3] presented the first quantitative data to show that diffuse damage can be repaired directly in vivo, without the intervening step of bone remodeling. They observed that the area of diffuse damage created by acute creep loading in rats was significantly reduced 14 days following the load, without any evidence of the activation of new intracortical resorption sites. Thus, the inverse association between diffuse damage and resorption found in the paper by Ural is probably incidental. Interestingly, Ural et al. found no age-independent association between linear microcrack density and resorption parameters even though it is well established now that the two are linked through the process of targeted remodeling [4, 5]. Accumulation of advanced glycation end-products (AGEs) in cortical bone occurs naturally with age [6], and may contribute to age-related skeletal fragility. AGEs form intrafibrillar collagen crosslink-like bonds and stiffen the collagen fiber matrix. They are the result of a series of D. B. Burr (*) Department of Anatomy andCell Biology, Indiana University School of Medicine, 635 Barnhill Dr, Indianapolis, IN 46202, USA e-mail: dburr@iupui.edu