Bone tissue is a tissue that is regenerated throughout life. And this regeneration process is called bone remodeling. Now the bone remodeling has two steps. The first step of the bone remodeling process is bone resorption. In the bone resorption step, special cells called osteoclasts break down bone. And the other step is the bone formation step. In the bone formation step, cells called osteoblasts form new bone. Thus, bone regeneration is ensured. However, a bone with Paget's disease has abnormalities in the bone remodeling process. In a bone with Paget's disease, osteoclasts first cause a high degree of bone resorption. Then the osteoblasts try to keep up by making new bone, but they overreact and make excess bone that is abnormally large and deformed.
The exact cause of Paget’s disease is unknown. However research findings suggest that Paget’s disease may be related to a “slow virus” infection of bone, a condition that is present for many years before symptoms appear. Associated viral infections include respiratory syncytial virus, canine distemper virus, and the measles virus. Paget's disease is also linked to genetic mutations such as the SQSTM1 gene mutation. Normally SQSTM1 gene encodes a protein involved in regulating osteoclasts.
When Paget's 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, Paget's disease has 3 phases. And the first phase is the lytic phase.
In lytic phase the number of osteoclasts increases. And also osteoclasts at this phase are larger than normal osteoclasts and have more nuclei. And these osteoclasts aggressively break down the bone up to 20 times more than normal.
The second phase is the mixed phase. Mixed phase is characterized by rapid increases in bone formation from numerous osteoblasts. Although increased in number, the osteoblasts remain morphologically normal. However the newly made bone is abnormal. Because collagen fibers deposited in a haphazard fashion rather than linearly, as with normal bone formation.
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”.
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.
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.
In many cases, Paget’s disease is discovered incidentally, when x-rays are taken or bloodwork is performed for some other reason. If this occurs, your doctor will perform a physical examination and order a number of tests like X-rays to confirm the diagnosis. X-rays provide images of dense structures, such as bone. Thus Paget’s disease can usually be diagnosed by looking at an x-ray. A bone affected by Paget’s usually appears larger and denser than a normal bone. It may also have a deformed shape.
A blood test called serum alkaline phosphatase may also be used to help confirm the diagnosis. In patients with Paget’s disease, alkaline phosphatase levels are usually quite elevated
A biopsy is sometimes necessary to confirm the diagnosis of Paget's disease or to rule out other conditions. In a biopsy, a small sample of the affected bone is removed and examined under a microscope. The procedure can be performed under local anesthesia with a needle or as a small open operation.
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.
