PTH(1‐34) effects on repairing experimentally drilled holes in rat femur: novel aspects – qualitative vs. quantitative improvement of osteogenesis

Abstract

The timetable of effects on bone repair of the active fraction-parathyroid hormone, PTH(1-34), was analytically investigated from the morphometric viewpoint in 3-month-old male Sprague-Dawley rats, whose femurs were drilled at mid-diaphyseal level (transcortical holes). The animals were divided into groups with/without PTH(1-34) administration, and sacrificed at different times (10, 28, 45 days after surgery). The observations reported here need to be framed in the context of our previous investigations regarding bone histogenesis (Ferretti et al. Anat Embryol. 2002; 206: 21-29) in which we demonstrated the occurrence of two successive bone-forming processes during both skeletal organogenesis and bone repair, i.e. static and dynamic osteogenesis: the former (due to stationary osteoblasts, haphazardly grouped in cords) producing preliminary bad quality trabecular bone, the latter (due to typical polarized osteoblasts organized in ordered movable laminae) producing mechanically valid bone tissue. The primary function of static osteogenesis is to provide a rigid scaffold containing osteocytes (i.e. mechano-sensors) for osteoblast laminae acting in dynamic osteogenesis. In the present work, histomorphometric analysis revealed that, already 10 days after drilling, despite the holes being temporarily filled by the same amount of newly formed trabecular bone by static osteogenesis independently of the treatment, the extent of the surface of movable osteoblast-laminae (covering the trabecular surface) was statistically higher in animals submitted to PTH(1-34) administration than in control ones; this datum strongly suggests the effect of PTH(1-34) alone in anticipating the occurrence of dynamic osteogenesis involved in the production of good quality bone (with more ordered collagen texture) more suitable for loading. This study could be crucial in further translational clinical research in humans for defining the best therapeutic strategies to be applied in recovering severe skeletal lesions, particularly as regards the time of PTH(1-34) administration.

WISP-2 expression induced by Teriparatide treatment affects in vitro osteoblast differentiation and improves in vivo osteogenesis

“…All these data highlighted the importance of Wisp-2 produced by osteocyte population in pushing osteogenesis process. Our results match also with the observations by Cavani and coworkers (Cavani et al, 2017) on PTH(1-34) effects during repairing experimentally drilled holes in rat femur, where the main effect of PTH(1-34) was demonstrated to be the induction of a faster healing of the bone lesions with respect to the injured rats that not underwent PTH Fig. 12.…”

Interaction among Calcium Diet Content, PTH (1-34) Treatment and Balance of Bone Homeostasis in Rat Model: The Trabecular Bone as Keystone

“…In fact, as Ferretti and coworkers clearly demonstrated, static osteogenesis (SO) is conditioned by vascular-derived inductive stimuli that do not appear to affect our experimental evidences; on the contrary, dynamic osteogenesis (DO) is conditioned by mechanical stimuli (sensed by osteocytes), which is in turn dependent on the increase of the body weight occurring in our experimental condition. These results are also fully in line with the demonstration that the crucial effect of PTH (1-34) is to improve only the “dynamic” bone formation instead of the “static” one during bone repair in transcortical holes experimentally drilled in rat femur [47]. On the contrary, in some pathologies, like facet joint osteoarthritis (FJOA), remodeling of the subchondral trabecular bone compartment is characterized by increased trabecular number, rather than trabecular thickening [48]; this observation can be explained with the impairment of viability of osteocytes (i.e., the bone mechanosensor) inside the trabecular bone due to osteoarthritis, so that static osteogenesis (instead of dynamic one) is activated, through the recruitment of osteoprogenitor cells by endothelial-derived growth factors, giving rise to the formation of new trabeculae.…”

Interplay among calcium diet content, PTH(1-34) treatment and balance of bone homeostases in rat model: the trabecular bone as keystone

“…In fact, as Ferretti and coworkers clearly demonstrated, static osteogenesis (SO) is conditioned by vascular-derived inductive stimuli that do not appear to affect our experimental evidences; on the contrary, dynamic osteogenesis (DO) is conditioned by mechanical stimuli (sensed by osteocytes), in turn dependent on the increase of the body weight occurring in our experimental condition. These results are also fully in line with the demonstration that the crucial effect of PTH(1-34) is to improve only the "dynamic" bone formation instead of the "static" one during bone repair in transcortical holes experimentally drilled in rat femur [47]. On the contrary, in some pathologies, like facet joint osteoarthritis (FJOA), remodeling of the subchondral trabecular bone compartment is characterized by increased trabecular number, rather than trabecular thickening [48]; this observation can be explained with the impairment of viability of osteocytes (i.e.…”