Premature loss of bone remodeling compartment canopies is associated with deficient bone formation: a study of healthy individuals and patients with Cushing's syndrome.

TY - JOUR

T1 - Premature loss of bone remodeling compartment canopies is associated with deficient bone formation: a study of healthy individuals and patients with Cushing's syndrome.

AU - Jensen, Pia Rosgaard

AU - Andersen, Thomas Levin

AU - Søe, Kent

AU - Hauge, Ellen Margrethe

AU - Bollerslev, Jens

AU - Amling, Michael

AU - Barvencik, Florian

AU - Delaissé, Jean-Marie

PY - 2012

Y1 - 2012

N2 - A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling were proposed to be critical players in this mechanism. Here, we provide support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces. Both cohorts showed almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above bone forming surfaces. This indicates that BRC canopies are invariably associated with the early stage of the remodeling cycle, but may disappear later. Interestingly, in control and two-thirds of the CS patients, a significant decline in canopy coverage occurred only once bone formation was initiated, but in the remaining third of the CS patients the prevalence of canopies already decreased before bone formation. This canopy loss before initiation of bone formation coincided with significantly less bone-forming surface compared with canopy loss at a later stage. These observations support a model where bone restitution is compromised in the absence of BRC canopies, and apparently does not start when the BRC canopy is lost before initiation of the bone formation step. This model is discussed in the context of possible biological roles of BRC canopies. It suggests that BRC canopies could be privileged targets for treating patients suffering from a negative bone formation-resorption balance.

AB - A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling were proposed to be critical players in this mechanism. Here, we provide support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces. Both cohorts showed almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above bone forming surfaces. This indicates that BRC canopies are invariably associated with the early stage of the remodeling cycle, but may disappear later. Interestingly, in control and two-thirds of the CS patients, a significant decline in canopy coverage occurred only once bone formation was initiated, but in the remaining third of the CS patients the prevalence of canopies already decreased before bone formation. This canopy loss before initiation of bone formation coincided with significantly less bone-forming surface compared with canopy loss at a later stage. These observations support a model where bone restitution is compromised in the absence of BRC canopies, and apparently does not start when the BRC canopy is lost before initiation of the bone formation step. This model is discussed in the context of possible biological roles of BRC canopies. It suggests that BRC canopies could be privileged targets for treating patients suffering from a negative bone formation-resorption balance.

M3 - SCORING: Journal article

VL - 27

SP - 770

EP - 780

JO - J BONE MINER RES

JF - J BONE MINER RES

SN - 0884-0431

IS - 4

M1 - 4

ER -