by new bone tissue.

Remodeling also occurs when reshaping your bones after a fracture or when repairing micro-cracks

which form during ordinary activities, especially when your bones are under stress, like after

lifting heavy weights.

Now the bones’ surface is covered by a layer called the periosteum except at the articular

cartilages - the parts involved in the joints.

The periosteum consists of an outer fibrous layer which protects the bones and provides

attachment for the tendons and the ligaments, and it also has an inner cellular layer which

houses progenitor stem cells.

These progenitor stem cells develop into both osteoblasts which secrete the bone matrix,

and chondroblasts - which produce cartilage.

Now let’s look at the femur - the longest bone in the body.

The two ends of the bone that forms the joints are called epiphysis, while the shaft of the

bone is called the diaphysis.

Looking at the diaphysis; or the bone shaft, it has an external part; the cortical bone,

which consists of many tiny cylinders known as osteons.

Each osteon is made of many lamellae, which are these concentric layers made of an organic

part - mostly collagen, and an inorganic part called hydroxyapatite, which is mostly calcium

phosphate.

In the center of every osteon is a Haversian canal, which contains the blood supply and

innervation for the bone cells.

In the center of the bone, is the medullary canal - a hollow space lined by a honeycomb-looking

structure called the spongy or cancellous bone.

The medullary canal contains the bone marrow, which is the site of blood cell production.

Now the epiphysis is made of a lot of spongy bone.

And when you look closer at the spongy bone, it’s made of crosslinking tiny roads called

trabeculae, which make your bones resistant to mechanical stress, so that they can bear

weights without caving in.

And just like the medullary cavity, the spaces in the spongy bone of the epiphysis are occupied

by bone marrow.

Now, let’s jump into the bone marrow.

That’s where we find the hematopoietic stem cells, the blood-making cells of the bone

marrow, which give rise to the lymphoid progenitor cells - which mature and differentiate into

lymphocytes like T and B cells, the main cells involved in your adaptive immunity, and the

myeloid progenitor cells, which differentiate into red blood cells, platelets, and myeloblasts

– the progenitors of basophils, neutrophils, eosinophils and monocytes.

There are a number of growth factors that help these cells develop.

For example, osteoblasts release a substance called M-CSF - Macrophage colony-stimulating

factor, which helps stimulate myeloid cells like monocytes.

Now in bone remodeling, the process begins when osteoblasts sense micro cracks at their

location, like when your bones are bearing much weight.

The osteoblasts produce a substance called RANKL - receptor activator of nuclear factor

κβ ligand, which binds to RANK receptors on the surface of nearby monocytes.

RANKL induces those monocytes to fuse together to form a multinucleated osteoclast cell.

RANKL also helps the osteoclast mature and activate so that they can start resorbing

bones.

The osteoclast starts secreting lysosomal enzymes – mostly collagenase, which digests

the collagen protein in the organic matrix.

This drills pits on the bone surface known as the Howship’s lacunae.

Osteoclasts also start producing hydrochloric acid - HCl, which dissolves hydroxyapatite

into soluble calcium – Ca2+ and phosphate – PO42- ions, and these ions get released

into the bloodstream.

There are also a scattering of osteocytes which are trapped within the bony matrix.

When these get freed up by the dissolving of bone, they get eaten up or phagocytosed

by the osteoclasts.

What a way to go!

Now to keep bone resorption under control, the osteoblasts also secrete Osteoprotegerin,

which binds to RANKL and prevents it from activating RANK receptors.

This slows down the activation of osteoclasts.

Finally, once osteoclasts complete their job, they commit suicide by means of apoptosis.

Following bone resorption, osteoblasts start secreting osteoid seam, a substance mainly

made of collagen, to fill in the lacunae created by the osteoclasts.

Calcium and phosphate begin to deposit on the seam, forming hydroxyapatite.

Also, as osteoblasts keep producing new bony material, many get trapped within tiny lacunae

within the bony matrix, and turn into osteocytes.

Bone remodeling is affected by various hormones.

The parathyroid glands, the four small pea-like structures located on the thyroid gland in

the neck, release parathyroid hormone in response to a drop in blood calcium levels.

The parathyroid hormone travels to the bones and stimulates the osteoblasts to release

RANKL, which triggers bone resorption.

This allows calcium ions-Ca2+ to be released into the bloodstream, and that corrects the

deficiency.

Now, when the blood calcium level is higher than normal, the parathyroid gland releases

less parathyroid hormone to have less bone resorption.

Now, in addition, parafollicular cells in the thyroid gland produces a hormone called

calcitonin.

High calcitonin levels inhibit bone resorption which results in lower blood calcium levels.

Another factor on bone remodeling is mechanical stress.

That’s why bones that bear a lot of weight remodel at such a high rate - a phenomenon

called Wolff’s law.

Next there’s Vitamin D which stimulates intestinal absorption of calcium, which then

causes calcitonin levels to increase and that inhibits bone resorption.

Alright, as a quick recap, we have seen that bone remodeling is a continuous process by

which bones are resorbed by osteoclasts, and remade by osteoblasts.

Osteoblasts release RANKL to initiate remodeling, and osteoprotegerin to help turn it off.

Bone remodeling is involved in repairing those tiny cracks in your bones due to normal activities,

and in helping bones heal after a fracture.