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Collagen and Bone Strength

BONE STRENGTH IS a complex property which we understand in only a limited and incomplete fashion. Bone density and bone strength are highly but imperfectly correlated. The relative amounts and properties of the mineral (apatite) and the organic matrix (mainly type I collagen) in bone, as well as the organization of the bone at both the microscopic and macroscopic scales (microarchitecture and anatomy, respectively), determine its mechanical strength. That there is a strong genetic component to bone density and, more generally, to bone strength is well established, but we still know relatively little about the contributions of specific genes to bone mineral content and bone strength. As we discuss below, the evidence for the importance of various candidate genes is uneven in its quality but is compelling in the case of the type I collagen genes. Readers of this journal know that bone is a metabolically active tissue, with bone resorption and deposition proceeding as ongoing processes. Bone modeling in response to load, as described by Wolff, enables bones to adapt their material structures to optimize both their mechanical properties and their mass. Osteoporosis in many but not all settings, including those associated with estrogen insufficiency, steroid use, nutritional abnormalities, or excessive exercise, develops when these opposing processes are unbalanced. Whether the cause is osteoblastic insufficiency or osteoclastic overactivity, the result at the tissue level is always a loss of bone mass/density and deleterious changes in bone architecture. At the inorganic molecular level, the smaller mineral crystals disappear, and the larger more brittle crystals persist. There is some suggestion that collagen structure and properties may also be altered at the organic level. In an article by Puustjärvi et al. on page 321 of this Journal issue, the authors probe the mechanism of bone loss associated with heavy exercise. They report that longterm running significantly reduced bone density in beagle dog vertebrae without changing the bone’s mechanical (indentation) properties. The authors suggest that changes in the orientation of the collagen network, without changes in collagen maturation (cross-linking) and content (hydroxyproline per tissue), contributed to the maintenance of strength in the face of decreased mineral density. The purpose of this commentary is to review additional documentation for that view while indicating the limitations of the present study. First, we briefly review genotypephenotype associations of collagen. Next, the impact of collagen mutations on the microscopic structure of the connective tissue are considered. Then, we summarize what is known relating these microarchitectural changes to biomechanical tests. Finally, we consider how Puustjärvi et al.’s paper fits into this background.