Front Matter

58 Canine Sports Medicine and Rehabilitation

the ECM while tensile stresses are resisted by
the organic component of the bone matrix,
primarily the collagen fibrils (Currey, 2008).
The walls of cellular lacunae and canaliculi as
well as the interfaces between individual
lamellae of osteons are important sites of stress
concentration within cortical bone. Most frac­
tures are thought to develop as tensile stresses
within the bone matrix lead to delamination of
osteonal lamellae, and subsequent propagation
and expansion of cortical microcracks.

Bone remodeling

Bone is a dynamic tissue that undergoes con­
tinual turnover throughout life. This remode­
ling process involves a highly regulated balance
between resorption of existing bone and depo­
sition of new bone (Sims & Gooi, 2008).
Adaptive remodeling is the process by which
the morphology and mechanical properties of a
bone are adjusted in response to  regional
mechanical strains. Adaptive remodeling of
bone is often referred to as Wolff’s law.

Bone remodeling involves the coordinated

activities of osteocytes, osteoclasts, and osteo­

blasts (Figure 3.11). This triad of cells is termed

the basic multicellular unit (BMU). Osteocytes

are the primary mechanosensors within bone.

Mechanical strains within the bone matrix

cause pressure changes and fluid flows within

the canaliculi of Haversian systems; these are

transduced by osteocytes into biological sig­

nals. Osteocytes form a highly interconnected

cellular network and communicate both with

adjacent osteocytes and with nearby endosteal

or periosteal osteoblasts through gap junctions

as well as through release of soluble mediators.

Physiological strains are trophic for osteocytes

and elicit release of the osteocyte‐specific pro­

tein sclerostin (Robling et al., 2008). Sclerostin is

an inhibitory mediator that downregulates the

activity of osteoblasts. The remodeling process

is triggered by the loss of osteocytes. This may

occur through direct trauma. Osteocytes may

also be lost by apoptosis, which is triggered by

supraphysiological strains, or by conditions of

very low strain such as occur with disuse and

Bone lining cell

Activation Resorption Reversal Deposition Te rmination

Osteoclast

Osteoclast

precursor

Osteomac

Osteoblast

Reversal cell

Sclerostin

Osteocyte

M-CSF

RANKL

Figure 3.11 Bone remodeling proceeds in five phases (depicted from left to right). During activation, matrix damage
causes loss of osteocytes and interruption of sclerostin signaling. Expression of RANKL (receptor activator of NFκB
ligand) and M‐CSF (monocyte colony‐stimulating factor) by bone lining cells leads to recruitment and differentiation of
osteoclast precursors. During resorption, mature osteoclasts demineralize and hydrolyze bone matrix within a
compartment lined by specialized mononuclear cells called osteomacs. Reversal involves enzymatic modification of the
surface of the resorption pit by reversal cells. During deposition, osteoblasts fill the bone defect with new osteoid.
The remodeling cycle is terminated when new osteocytes resume negative regulatory sclerostin signaling to adjacent
lining cells and osteoblasts.