Understanding Coupling between Bone Resorption and Formation

A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

“…The present notion is that the osteoporotic bone loss either results from an unbalanced bone remodelling process, where the resorbed bone matrix is not completely substituted with a new bone matrix by bone forming OBs [13], or from an uncoupled bone remodelling process, where the initiation of the bone formation following the bone resorption is prevented during the reversal phase [21,23,24]. In both postmenopausal and glucocorticoid-induced osteoporosis an uncoupled bone remodelling process has been shown to result in a decreased extent of the formative osteoid surfaces (OS) and in an accumulation of the reversal surfaces (Rv.S) [20,23,24]. Here the accumulating reversal surfaces appeared arrested without the neighbouring OCs and OS, which is usually observed next to the active Rv.S.…”

“…3.5-μm adjacent paraffin sections were either Masson's Trichrome stained [21] or immunostained [20]. The immunostained sections were labelled with mouse anti-tartrate-resistant acid phosphatase (TRAcP) IgG2b (clone 9C5, MABF96; Millipore Cooperation, Billerica, MA, USA), IgG2a smooth muscle actin (SMA) (clone 1A4; Dako, Glostrup, Denmark), anti-osterix (Sp7; Abcam, Cambridge, UK) or anti-Runx2 IgG2b (clone 1D8, ab115899; Abcam) antibodies, which were subsequent detected with alkaline phosphatase-conjugated anti-mouse polymers (Immunologic, Duvien, The Netherlands).…”

“…The histomorphometric analysis was conducted on a single set of vertical adjacent sections that were either Masson's Trichrome stained or immunostained for the OC marker TRAcP [20]. The extent of eroded surfaces (ES/BS), osteoid surfaces (OS/BS), OC surfaces (Oc.S/BS) and reversal surfaces (Rv.S/BS) were addressed by counting the number of intercepts between a cycloid grid and the respective bone surfaces (BS).…”

“…The reversal phase is recognised as eroded/reversal surfaces colonised by mononuclear osteoblastic reversal cells (Rv.Cs), which are believed to prepare the eroded surfaces for the subsequent bone formation [17][18][19]. Both the reversal phase and the canopies have been reported to be key players in the coupling of bone formation to resorption [20][21][22]. The present notion is that the osteoporotic bone loss either results from an unbalanced bone remodelling process, where the resorbed bone matrix is not completely substituted with a new bone matrix by bone forming OBs [13], or from an uncoupled bone remodelling process, where the initiation of the bone formation following the bone resorption is prevented during the reversal phase [21,23,24].…”

The dynamic skeleton

“…"Reversal cells" resorb collagen remnants and mediate the transition from osteoclastic bone resorption to osteoblastic bone formation [34]. The exact origin of these cells has been the subject of debate and although originally thought to be a monocyte-phagocyte [35], most recent findings suggest an osteoblast origin [36].…”