Dennis R. Carter

Skeletal regeneration is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, endochondral ossification, and bone remodeling. It has been shown that all these processes are influenced strongly by the local tissue mechanical loading history. This article reviews some of the mechanobiologic principles that are thought to guide the differentiation of mesenchymal tissue into bone, cartilage, or fibrous tissue during the initial phase of regeneration. Cyclic motion and the associated shear stresses cause cell proliferation and the production of a large callus in the early phases of fracture healing. For intermittently imposed loading in the regenerating tissue: (1) direct intramembranous bone formation is permitted in areas of low stress and strain; (2) low to moderate magnitudes of tensile strain and hydrostatic tensile stress may stimulate intramembranous ossification; (3) poor vascularity can promote chondrogenesis in an otherwise osteogenic environment; (4) hydrostatic compressive stress is a stimulus for chondrogenesis; (5) high tensile strain is a stimulus for the net production of fibrous tissue; and (6) tensile strain with a superimposed hydrostatic compressive stress will stimulate the development of fibrocartilage. Finite element models are used to show that the patterns of tissue differentiation observed in fracture healing and distraction osteogenesis can be predicted from these fundamental mechanobiologic concepts. In areas of cartilage formation, subsequent endochondral ossification normally will proceed, but it can be inhibited by intermittent hydrostatic compressive stress and accelerated by octahedral shear stress (or strain). Later, bone remodeling at these sites can be expected to follow the same mechanobiologic adaptation rules as normal bone.

We studied the acquisition of bone mineral in 45 healthy prepubertal and pubertal girls and related changes in bone mass to age, body mass, pubertal status, calcium intake, and exercise. A subgroup of 12 girls was followed longitudinally. Bone mineral content (BMC) of the lumbar spine, whole body, and femoral neck was measured by dual energy x-ray absorptiometry and that at the midradius by single photon absorptiometry. For comparison, spine and whole body mineral contents were also measured by dual photon absorptiometry. Bone mass was expressed in conventional terms of BMC and area density (BMD). However, we show that BMD fails to account for differences in bone thickness. Since bone size increases during adolescence, we present a new expression, bone mineral apparent density (BMAD), which is BMC normalized to a derived bone reference volume. This term minimizes the effect of bone geometry and allows comparisons of mineral status among bones of similar shape but different size. BMC increased with age at all sites. These increases were most rapid in the early teens and plateaued after 16 yr of age. When bone mineral values at all sites were regressed against age, height, weight, or pubertal stage, consistent relationships emerged, in which BMC was most strongly correlated, BMD was correlated to an intermediate degree, and BMAD correlated only modestly or without significance. Dietary calcium and exercise level did not correlate significantly with bone mass. From these relationships, we attribute 50% of the pubertal increase in spine mineral and 99% of the change in whole body mineral to bone expansion rather than to an increase in bone mineral per unit volume. In multiple regressions, pubertal stage most consistently predicted mineral status. This study emphasizes the importance of pubertal development and body size as determinants of bone acquisition in girls. BMAD may prove to be particularly useful in studies of bone acquisition during periods of rapid skeletal growth.

The compressive strength of bone is proportional to the square of the apparent density and to the strain rate raised to the 0.06 power. This relationship is applicable to trabecular and compact bone, and provides clinical guidelines for predicting bone strength on the basis of x-ray and densitometric examination.