Paget disease of bone

Definitions & Key takeaways

Paget's disease of bone, also known as osteitis deformans, is a chronic bone disorder that causes the bone to become thick, weak, and deformed. It commonly affects the pelvis, femur, and lower lumbar spine though it can affect any bone in the body.

Paget disease is associated with an increased risk of fractures, arthritis, and bone tumors. Symptoms may include pain in the affected bone or due to arthritis or nerve impingement. Treatment involves medications to slow the progression of the disease, such as bisphosphonates, pain relievers, and surgery to correct deformities or stabilize fractures.

Chapters:

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Introduction0:00–0:20

Paget disease of bone is a disorder in which there’s a lot of bone remodeling that happens in some regions of the bone. Typically there’s excessive bone resorption followed by excessive bone growth, and it leads to skeletal deformities and potential fractures.

Physiology0:20–1:52

Normally, bones undergo a continuous process of bone remodeling. Old brittle bone tissue gets reabsorbed by multinucleated bone cells called osteoclasts, which have 5 to 20 nuclei per cell.
The resorbed bone tissue gets replaced by a new one made by another type of bone cell called an osteoblast. At the cellular level, the process begins when osteoblasts release receptor activator of nuclear factor κβ ligand, or RANKL for short, which is a substance that binds to RANK receptors on the surface of osteoclast.
When RANKL binds to the RANK receptor, it activates the osteoclasts, and they start secreting lysosomal enzymes like collagenase as well as hydrochloric acid.
Together they digest the collagen protein and dissolve the minerals that make up the bone matrix. Once there’s been sufficient bone demineralization, the osteoblasts secrete another substance called Osteoprotegerin, or OPG for short, which binds RANKL and prevents it from activating the RANK receptors.
This causes the osteoclasts to stop demineralizing the bones. Once that happens, the osteoblasts start secreting a substance called osteoid seam, which is mainly made up of collagen and acts like a scaffold upon which calcium and phosphate can get deposited.
And that’s how new bone begins to get formed again. The exact cause of Paget disease of bone is unclear, but it can get triggered by infections like the measles virus, and is linked to genetic mutations like the SQSTM1 mutation, which encodes a protein involved in regulating osteoclasts.

Causes1:52–2:24

When Paget disease of bone occurs, it can affect a single bone or the whole skeletal system. Most often, it involves the skull, lumbar vertebrae, the pelvis, and the femur.

Pathology2:24–3:28

Now, there are three main phases to the disease. Phase one is the lytic phase, and that’s where osteoclasts, which have up to 100 nuclei, start to aggressively demineralize the bone up to 20 times more than normal.
Phase two is the mixed phase, and that’s where the lytic phase occurs alongside the blastic phase. In the blastic phase, there’s a rapid but relatively disorganized proliferation of new bone tissue by an unusually large number of osteoblasts.
The result is that collagen fibers are deposited in a haphazard way. Phase three is the sclerotic phase, and that’s where new bone formation exceeds bone resorption, and the final result is bone that’s structurally disorganized and therefore weaker than normal healthy bone.
Eventually, the osteoblastic activity also slows down, and there’s a dormant state in the disease, called the “burned- out state”.

Symptoms3:28–4:52

Early on Paget disease of bone doesn’t typically cause symptoms, but over time, the misshapen bones can impinge on nerves and cause pain.
In addition, if the skull is involved, the overgrowth of bones can make a person have a lion- like face, which is called leontiasis.
The bony overgrowth can also narrow the auditory foramen and impingement on the auditory nerve, leading to hearing loss.
If there’s bony overgrowth that impinges on the optic nerve as it passes through the optic canal - that can lead to vision loss.
Sometimes the accelerated bony growth can lead to genetic mutations that cause a bone cancer called osteosarcoma. When that happens it’s referred to as Paget sarcoma.
Other bony deformities from Paget disease of bone include kyphosis – which is an excessive curvature of the spine making a person face down to the ground, lower limb muscle weakness – from misshapen vertebrae compressing the spinal cord, and pelvic asymmetry.
It can even lead to bowlegs if the femurs get too weak to support a person’s weight and begin to bend over time. If the parts of the bone that are involved in a joint are involved, it can result in arthritis or joint inflammation.

Diagnosis4:52–5:19

The diagnosis of Paget disease of bone is usually done by checking for elevated levels of alkaline phosphatase. In addition, an X-ray might show lytic lesions during the lytic phase of the disease, or thickened bone cortices in advanced cases.
Finally, a bone biopsy is usually done to exclude malignancies which can mimic some of the findings of Paget disease of bone.

Treatment5:19–5:40

Treatment of Paget disease of bone includes pain relievers as well as antiresorptive medications like bisphosphonates which slow down the bone lysis.
In addition, surgery can help correct bone deformities, decompress an impinged nerve, and reduce associated fractures. Alright, as a quick recap, … in Paget disease of bone there’s an excessive amount of bone resorption and haphazard bone growth.

Review5:40–6:06

There’s a lytic phase, a mixed phase with both a lytic and blastic component, and a sclerotic phase which results in weak bone.
Paget disease of bone is usually asymptomatic, but can result in weak, misshapen bones that cause fractures and lead to nerve compression.