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Bone remodelling in a nutshell

Posted in Bone Disease and Musculoskeletal Disease, Cell Biology, Signaling & Cell Circuits, Nitric Oxide in Health and Disease, tagged adaptation, bone architecture, bone mass, bone physiology, bone remodelling, haemostasis, mechanical loading, mechanosensation, mechanosensitive, osteoblasts, osteoclasts, osteocytes on June 22, 2012| 11 Comments »

Author: Aviral Vatsa, Ph.D., MBBS

Bone is a highly dynamic tissue that responds to changes in its external environment. Our bones adapt their mass and architecture according to the external mechanical loading conditions. Any long term alterations in loading conditions result in alteration of bone mass and architecture. This is highlighted in the following examples:

Astronauts tend to lose their bone when they are in space. This is because the bones are not mechanically loaded externally due to absence of or reduction in gravitational force.
Tennis players gain more mass in their playing forearm as compared to the non-playing forearm.

In both these examples bones tend to readjust their internal structural mass and alignment as per the external loads or their absence. How bones can achieve this? How bone forming and bone resorbing cells can be orchestrated to bring about this adaptation?

Bone cells

The questions mentioned above can be answered by knowing more about the cellular components of bone and their functions. Our bones primarily have four cell types: osteocytes, osteoblasts, osteoclasts and bone lining cells. Osteocytes are believed to be the ‘professional’ mechanosensors of bone i.e. they sense the external loads put on bone. Osteoblasts are the bone forming cells. Osteoclasts are the bone resorbing cells and as the name suggests, bone lining cells line the bone surfaces and play a role in regeneration of osteogenic cells. Osteocytes, following mechanical loading, secrete signalling molecules such as nitric oxide (besides others). These signalling molecules then modulate the activity of bone forming osteoblasts and/or bone resorbing osteoclasts. Thus osteocytes orchestrate this process wherein adequate bone mass and architecture is achieved in accordance with the external loading conditions.

Anatomically, the osteocytes reside with in the hard bony matrix. They are the majority cell types in bone and are ideally placed to sense the mechanical loads. Osteocytes have a cell body and from the cell body arise nearly fifty cell processes. Through these cell processes each osteocyte forms a network with the surrounding osteocytes. Through this network, following mechanical loading, osteocytes can stimulate the activity of osteoblasts and inhibit the activity of osteoclasts. This process of maintenance of bone mass and architecture is called bone remodelling. Bone remodelling occurs through out our life. It occurs in response to microfractures, which can appear in our bone without being noticed clinically. As long as our bone metabolism is physiologically normal these stimuli, such as microfractures, result in bone remodelling.

In diseases such as osteoporosis, the mechanism of bone remodelling is disrupted and there is more bone resorbtion than new bone formation thus leading to reduction in bone mass and alteration of bone architecture. Drug therapies for osteoporosis such as bisphosphonates, act by inhibiting the activity of osteoclasts thereby resulting in reduction in bone resorbtion and hence helping in maintenance of adequate bone mass and architecture. Newer therapies that target to modulate a part of bone remodelling are being investigated.