Changes in bone matrix properties with aging.

It is well known that bone loss accompanies aging in both men and women and contributes to skeletal fragility in the older population, but changes that occur to the bone tissue matrix itself are less well known. These changes in bone quality aggravate the skeletal fragility associated with loss of bone mass. Bone tissue quality is affected by age-related changes in bone mineral, collagen and its cross-linking profiles, water compartments and even non-collagenous proteins. It is commonly assumed that greater tissue mineralization accompanies aging as bone turnover slows down in elderly individuals, but the data for this are weak. However, there may be changes in the quality of the mineral crystals, and the substitutions found within the crystal. Both enzymatically-mediated and non-enzymatically-mediated collagen cross-links multiply with age. The former tend to make the bone stiffer and stronger, but the latter, while making the bone stiffer can also make it more brittle and more likely to fracture. Bone pore water that is not bound to collagen or mineral increases with age as bone mass is lost, but water that is bound to collagen and mineral declines with age. These changes contribute to skeletal fragility by reducing the amount that bone can deform before fracturing. Finally, non-collagenous proteins have physical properties that can alter matrix mechanical properties and can also have molecular signaling functions that regulate bone remodeling. Whether these change with age, how they change, and how this affects skeletal fragility with aging is still largely a black box, and requires much more investigation. The roles of any of these factors in skeletal fragility are difficult to assess clinically as there is no easy or economical way to evaluate them, but a picture of fragility in the aging skeleton is incomplete without them.