Estimation of an early meaningful time point of bone parameter changes in application to an osteoporotic rat model with in vivo microcomputed tomography measurements

Abstract

The commonly used preclinical animal model of postmenopausal osteoporosis is the mature ovariectomized rat, whereby cessation of ovarian oestrogen production consequently results in bone volume reduction. The study aim was to precisely define the time course of structural changes resulting from ovariectomy and thereby reduce the time animals have to be treated to judge the effects of osteoporosis treatment. For this purpose, we assessed architectural changes by microcomputed tomography (mCT) during 10 weeks following ovariectomy or sham surgery at two-week intervals. Moreover, the trabecular microarchitecture of the lumbar vertebrae was assessed after necropsy. Besides this, serum biomarkers of bone turnover were determined. These data were in a new approach additionally correlated to femur mRNA expression profiles. We selected the osteoblast marker genes osteocalcin and type I collagen as well as the two osteoclast marker genes cathepsin k and tartrate-resistant acid phosphatase 5. The gene expression analysis suggested an activation of osteoblasts as well as octeoclasts. The significantly induced serum levels of osteocalcin and collagen degradation fragments also revealed this higher rate of bone turnover. Our results indicate that as soon as four weeks after ovariectomy the bone volume fraction exhibited a decline of 30% and 50% of the connectivity density. In addition, significant decreases of trabecular number and thickness as well as of the bone volume fraction were only observed in vertebrae of ovariectomized animals. Interestingly, changes of trabecular morphology were also found in the sham animals as a consequence of senescence.

Histological study of the femur and the lumbar vertebrae in ovariectomized adult albino rats following administration of collagen hydrosylate

“…This pattern is quite similar to that observed in OVX animals [14], as well as in postmenopausal osteoporotic women, in which a general increase in biochemical markers of This pattern is quite similar to that observed in OVX animals [14], as well as in postmenopausal osteoporotic women, in which a general increase in biochemical markers of…”

“…The mature ovariectomized (OVX) rat is the most commonly used preclinical experimental model of postmenopausal osteoporosis, whereby cessation of ovarian estrogen production consequently results in bone volume reduction [14].…”

Foreign body giant cells and osteoclasts are TRAP positive, have podosome‐belts and both require OC‐STAMP for cell fusion

“…We have shown that FBGCs grown for 4 days remain TRAP negative, but when the culture period was extended to 8 days, FBGCs became positive for TRAP staining. TRAP is an important marker of osteoclast activity [Keiler et al, 2012], and OCs from mice lacking TRAP staining were dysfunctional, resulting in an osteopetrotic phenotype [Hayman et al, 1996]. IL‐4, involved in the induction of FBGCs, suppresses RANKL‐mediated TRAP expression, but also increases TRAP expression in the absence of RANKL [Yu et al, 2009].…”

Influence of estrogen on individual exercise motivation and bone protection in ovariectomized rats

“…16 Partial prevention of ovx-induced osteopenia by weight increase, although previously reported, 17 was not supported by several recent studies. 13,18 In addition, our data show irreversible changes within the bone microarchitecture (Figure 2, Supplementary Material 1).…”