20 research outputs found
Bone refilling in cortical bone multicellular units: Insights into tetracycline double labelling from a computational model
Bone remodelling is carried out by `bone multicellular units' (BMUs) in which
active osteoclasts and active osteoblasts are spatially and temporally coupled.
The refilling of new bone by osteoblasts towards the back of the BMU occurs at
a rate that depends both on the number of osteoblasts and on their secretory
activity. In cortical bone, a linear phenomenological relationship between
matrix apposition rate (MAR) and BMU cavity radius is found experimentally. How
this relationship emerges from the combination of complex, nonlinear
regulations of osteoblast number and secretory activity is unknown.
Here, we extend our previous mathematical model of cell development within a
single BMU to investigate how osteoblast number and osteoblast secretory
activity vary along the BMU's closing cone. MARs predicted by the model are
compared with data from tetracycline double labelling experiments. We find that
the linear phenomenological relationship observed in these experiments between
MAR and BMU cavity radius holds for most of the refilling phase simulated by
our model, but not near the start and end of refilling. This suggests that at a
particular bone site undergoing remodelling, bone formation starts and ends
rapidly. Our model also suggests that part of the observed cross-sectional
variability in tetracycline data may be due to different bone sites being
refilled by BMUs at different stages of their lifetime. The different stages of
a BMU's lifetime depend on whether the cell populations within the BMU are
still developing or have reached a quasi-steady state while travelling through
bone. We find that due to their longer lifespan, active osteoblasts reach a
quasi-steady distribution more slowly than active osteoclasts. We suggest that
this fact may locally enlarge the Haversian canal diameter (due to a local lack
of osteoblasts compared to osteoclasts) near the BMU's point of origin.Comment: 16 pages, 6 figures, 3 tables. V3: minor changes: added 2 paragraphs
(BMU cavity in Section 2 and Model Robustness in Section 4), references
[52,54
A predator–prey based mathematical model of the bone remodelling cycle: Exploring the relationship between the model parameters and biochemical factors
© IMechE 2014. Bone remodelling is a vital process which enables bone to repair, renew and optimize itself. Disorders in the bone remodelling process are inevitably manifested in bone-related diseases, such as hypothyroidism, primary hyperparathyroidism and osteoporosis. In our previous work, a predator-prey based mathematical model was developed to simulate bone remodelling cycles under normal and two pathological conditions, hypothyroidism and primary hyperparathyroidism, for trabecular bone at a fixed point. However, the biochemical meanings of the model parameters were not fully explored. This article first extends the previous work by proposing relationships between the model parameters and biochemical factors involved in the bone remodelling process and by examining whether those relationships do predict the behaviours observed in vivo. The model is then applied to the simulation and investigation of bone remodelling of postmenopausal osteoporosis. The proposed connections are supported by good agreement between the model simulations and published experimental observations for the normal condition and all three pathological variations in bone remodelling