Frequency of Teriparatide Administration Affects the Histological Pattern of Bone Formation in Young Adult Male Mice

Evidence supports that daily and once-weekly administration of teriparatide, human (h)PTH(1–34), enhance bone mass in osteoporotic patients. However, it is uncertain whether different frequencies of hPTH(1–34) administration would induce bone formation similarly in terms of quantity and quality. To investigate that issue, mice were subjected to different frequencies of PTH administration, and their bones were histologically examined. Frequencies of administration were 1 time/2 days, 1 time a day, and 2 and 4 times a day. Mice were allocated to either to control or to 3 different dosing regimens: 80 μg/kg of hPTH(1–34) per injection (80 μg/kg per dose), 80 μg/kg of hPTH(1–34) per day (80 μg/kg · d), or 20 μg/kg of hPTH(1–34) per day (20 μg/kg · d). With the regimens of 80 μg/kg per dose and 80 μg/kg · d, high-frequency hPTH(1–34) administration increased metaphyseal trabecular number. However, 4 doses per day induced the formation of thin trabeculae, whereas the daily PTH regimen resulted in thicker trabeculae. A similar pattern was observed with the lower daily hPTH(1–34) dose (20 μg/kg · d): more frequent PTH administration led to the formation of thin trabeculae, showing a thick preosteoblastic cell layer, several osteoclasts, and scalloped cement lines that indicated accelerated bone remodeling. On the other hand, low-frequency PTH administration induced new bone with mature osteoblasts lying on mildly convex surfaces representative of arrest lines, which suggests minimodeling-based bone formation. Thus, high-frequency PTH administration seems to increase bone mass rapidly by forming thin trabeculae through accelerated bone remodeling. Alternatively, low-frequency PTH administration leads to the formation of thicker trabeculae through bone remodeling and minimodeling.

Finite Element Modeling of Microcrack Growth in Cortical Bone

Bone is similar to fiber-reinforced composite materials made up of distinct phases such as osteons (fiber), interstitial bone (matrix), and cement lines (matrix-fiber interface). Microstructural features including osteons and cement lines are considered to play an important role in determining the crack growth behavior in cortical bone. The aim of this study is to elucidate possible mechanisms that affect crack penetration into osteons or deflection into cement lines using fracture mechanics-based finite element modeling. Cohesive finite element simulations were performed on two-dimensional models of a single osteon surrounded by a cement line interface and interstitial bone to determine whether the crack propagated into osteons or deflected into cement lines. The simulations investigated the effect of (i) crack orientation with respect to the loading, (ii) fracture toughness and strength of the cement line, (iii) crack length, and (iv) elastic modulus and fracture properties of the osteon with respect to the interstitial bone. The results of the finite element simulations showed that low cement line strength facilitated crack deflection irrespective of the fracture toughness of the cement line. However, low cement line fracture toughness did not guarantee crack deflection if the cement line had high strength. Long cracks required lower cement line strength and fracture toughness to be deflected into cement lines compared with short cracks. The orientation of the crack affected the crack growth trajectory. Changing the fracture properties of the osteon influenced the crack propagation path whereas varying the elastic modulus of the osteon had almost no effect on crack trajectory. The findings of this study present a computational mechanics approach for evaluating microscale fracture mechanisms in bone and provide additional insight into the role of bone microstructure in controlling the microcrack growth trajectory.

The Effect of Cement Line Properties and Crack Orientation on Crack Propagation in Cortical Bone

Microstructural features such as osteons and cement lines are considered to play an important role in determining the crack growth behavior in cortical bone. Cracks that penetrate the osteons may lead to complete failure of the bone [1]. On the other hand, the cracks that are deflected into the cement line slow down the crack propagation and increase the crack resistance of the bone. Although various factors were reported in the literature [1–4], the underlying mechanisms of crack propagation behavior in cortical bone have not been completely understood.