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Paget disease of bone



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Paget disease of bone


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High Yield Notes
16 pages

Paget disease of bone

22 flashcards

USMLE® Step 1 style questions USMLE

2 questions

A 65-year-old man comes to the office because of deep and aching hip pain. The pain is constant throughout the day and worsens with weight-bearing activity. The patient also reports that his shoe size has increased over the past year, and he has progressively lost hearing from both ears. Medical history includes admission for a renal calculus one-month ago. Laboratory investigations demonstrate an isolated increase in serum alkaline phosphatase. A pelvic x-ray is obtained, and the results are as follows:

Reproduced from: Wikimedia Commons

The patient’s current condition places him at risk of developing which of the following pathologies?  

External References

Content Reviewers:

Rishi Desai, MD, MPH

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.

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.

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.

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.


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.

  1. "Robbins Basic Pathology" Elsevier Canada (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 7/E (ENHANCED EBOOK)" McGraw Hill Professional (2014)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Paget's Disease of Bone" New England Journal of Medicine (2013)
  6. "Epidemiology and pathology of Paget’s disease of bone – a review" Wiener Medizinische Wochenschrift (2016)
  7. "Pathogenesis of Paget Disease of Bone" Calcified Tissue International (2012)