Paget's Disease of Bone is second most common disease caused by genetics and environmental factors. Bisphosphonates are helpful in Paget's disease treatment.

Paget’s Disease Of The Bone

Online Consultation

Iqra Mazhar

Overview

Paget&#39;s disease of bone (PDB), also known as osteitis deformans, refers to a localized skeletal disorder which may involve either a single bone or multiple bones. Most of the patients going through PDB are asymptomatic. However, significant symptoms which include bone pain, bone deformity, secondary <a href="https://www.merisehat.pk/disease/arthritis" target="_blank">arthritis </a>(inflammation of the joints due to a pre-existing condition), and neurologic problems may occur in a few<a href="#accordion">[1]</a>.&nbsp; 
&nbsp;

PDB has proven to be the second most common type of bone disease. The bone disorder involves remodeling of the bone, i.e., its structural integrity becomes compromised and the outlook of the bone changes. While osteoporosis enjoys the primary rank, the disease is prevalent in around 1&ndash;2% of white adults aged older than 55 years<a href="#accordion">[1]</a>.

Furthermore, a study done on the archaeological skeletons of Northern England origin found a prevalence of 2.1% in people older than 40 years of age. The study also concluded that the prevalence of PDB was directly proportional to age with a slight predilection in men. According to a survey, PDB is rare in those under 25 years of age and not usually seen before 40 years. To support this, a survey of 864 patients proved that the mean age at which people were diagnosed was 58 years<a href="#accordion">[1]</a>.

While analyzing the prevalence, it can be seen that it varies on the basis of ethnicity and geographic limitations. The disease is mostly seen in the United Kingdom and Western Europe. However, it is also common in people who migrate to Australia, New Zealand, South Africa, and South America from Britain. However, the disease is less common in China, Japan, and Southeast Asia. Furthermore, researchers have found compelling evidence that the incidence and severity of PDB in the United Kingdom and New Zealand have been decreasing over the past 25-30 years<a href="#accordion">[1]</a>.

The primary lesion in the PDB is an increase in osteoclastic activity which causes bone resorption. Following bone resorption, the osteoblasts cause bone formation. This accelerated bone-making and breaking increases the overall turnover, and the new collagen fibers are not placed in a formal linear fashion. Hence, giving a disorganized impression. As a result, the bone shows a mosaic of woven and lamellar bone with poor mechanical integrity. This increases the patient&rsquo;s risk for fracture and deformity. Moreover, Paget&#39;s disease of the bone has shown a predilection for the axial skeleton which is essentially made up of the bones in your head, neck, back, and chest. PDB is seen to commonly affect the pelvis and spine, and in particular, the lumbar spine. Statistics show a frequency of 30-75% when it comes to PDB affecting the lumbar spine. The involvement of the sacrum is reported in 30-60% of cases and the skull in 25-65% of cases<a href="#accordion">[2]</a>. 
&nbsp;

There are essentially two types of PDB: monostotic and polyostotic. While monostotic refers to the involvement of a single bone, polyostotic refers to the involvement of multiple bones<a href="#accordion">[2]</a>. 
&nbsp;

Signs And Symptoms

Although patients with PDB are usually asymptomatic, when symptoms do occur, the patients usually complain of pain in their bones. PDB has the tendency to affect either one or two areas of your body, but it can be a widespread disease too. Thus, signs and symptoms of PDB are dependent on the area involved.

&nbsp;

<ul>
	<li>Pelvis: If your pelvis is involved, the patient can complain of hip pain.</li>
	<li>Skull: Skull involvement can lead to an overgrowth of the skull bone and cause hearing loss or headaches.</li>
	<li>Spine: If a patient&rsquo;s spine is involved, compression of nerve roots i.e. where our nerves originate from, can lead to pain, tingling sensation, and numbness in an arm or leg, depending on which nerve is compromised.</li>
	<li>Leg: Bones are an extremely tough structure. However, upon weakening, they may bend out of shape and lose their integrity which in turn causes bowlegs. Furthermore, due to the loss of structural integrity, enlarged bones of your legs put unnecessary stress on the adjacent joints as well, leading to osteoarthritis of the knee or hip. 
	&nbsp;</li>
</ul>

Causes

Researchers have not concluded what exactly causes Paget&rsquo;s disease, but it is believed that the genes passed on through families might play a crucial part. Moreover, factors such as poor diet and bone injury in the early years of life may initiate the onset of Paget&rsquo;s disease in people who are at genetic risk. 
&nbsp;

Although there are no specific tests to screen a person for Paget&rsquo;s disease of the bone, a detailed history of the parents along with the relevant signs and symptoms presented by the patient can warrant diagnostic tests to be carried out. 
&nbsp;

Diagnosis

To diagnose someone with Paget&rsquo;s disease of the bone, a number of diagnostic tests can be used. Some of those tests include<a href="#accordion">[3]</a>:

&nbsp;

<ul>
	<li>
	<h5>Alkaline&nbsp;Phosphatase&nbsp;Test</h5>
	</li>
</ul>

Alkaline Phosphatase (ALP) levels are estimated by a blood test. High levels are a sign that you have Paget&rsquo;s disease of the bone. It is considered one of the earliest signs of Paget&rsquo;s disease.

&nbsp;

<ul>
	<li>
	<h5>X-Rays</h5>
	</li>
</ul>

X-ray is an excellent diagnostic modality when it comes to bones as it provides detailed results. With X-ray images, your doctor aims to assess if your bones are under the influence of Paget&rsquo;s disease.

&nbsp;

<ul>
	<li>
	<h5>Bone&nbsp;Scan</h5>
	</li>
</ul>

Your healthcare provider may use a bone scan to see which of the bones are affected and to assess its severity. A bone scan is done by injecting a safe amount of radioactive liquid into your veins. The liquid then flows through your bloodstream to your bones making the bones affected by Paget&rsquo;s disease prominent. These bones appear &ldquo;bright&rdquo; on your scan. 
&nbsp;

Treatment

Paget&rsquo;s disease of the bone should not be taken lightly even though it may present asymptomatically. Any disease should be treated in due time and not be prolonged unnecessarily. Paget&rsquo;s disease of the bone can be tackled by medicines as well as by surgical intervention<a href="#accordion">[4]</a>.&nbsp;

&nbsp;

<h5>1. Medications</h5>

Common osteoporosis drugs like bisphosphonates (e.g. alendronate) are mostly used to treat Paget&#39;s disease of bone. Bisphosphonates are typically administered via an injection into a vein. However, they can also be taken orally.

&nbsp;

Intravenous bisphosphonates include:

<ul>
	<li>Zoledronic acid</li>
	<li>Pamidronate</li>
	<li>Ibandronate</li>
</ul>

&nbsp;

Oral bisphosphonates include:

<ul>
	<li>Alendronate</li>
	<li>Risedronate</li>
</ul>

&nbsp;

Side effects of bisphosphonates should be discussed with your doctor as they can sometimes cause severe muscle, joint, or bone pain, which may persist even when the medication is discontinued. Bisphosphonates are also responsible for possibly increasing the risk of the necrosis of the jawbone, however, this is an uncommon occurrence.

If for some reason, you are not able to tolerate bisphosphonates, your healthcare provider might prescribe you calcitonin, which is essentially a hormone that regulates calcium and bone metabolism. While calcitonin is administered by injection or nasal spray, its side effects include nausea, facial flushing (redness of the cheeks), and irritation at the injection site.

&nbsp;

<h5>2. Surgery</h5>

Surgical intervention is rarely needed and is only indicated under special circumstances. Some of these situations include:

<ul>
	<li>When there is a fracture that needs some aid to heal</li>
	<li>Replacement of joints is needed due to the damage caused by severe arthritis</li>
	<li>Realignment of any deformed bones</li>
	<li>When there is a need for a reduction in pressure that might be exerted on your nerves</li>
</ul>

Note: In Paget&#39;s disease of the bone, your body produces excess blood vessels in the affected bones, which may increase the risk of potentially fatal blood loss during any surgical operation. 
&nbsp;

Paget&#39;s disease of bone is considered a slow-progressing disease, but if not managed effectively, it may cause the following complications<a href="#accordion">[5]</a>:

&nbsp;

<ul>
	<li>
	<h5>Fractures&nbsp;And&nbsp;Deformities</h5>
	</li>
</ul>

Affected bones lose their structural integrity and are more prone to break. Furthermore, excessive blood vessels in these restructured bones can cause them to bleed a lot if any surgeries are planned. Bow-leggedness is a condition in which leg bones can bow, affecting your ability to walk.

&nbsp;

<ul>
	<li>
	<h5><a href="https://www.merisehat.pk/disease/osteoarthritis-64627" target="_blank">Osteoarthritis</a></h5>
	</li>
</ul>

Misshapen bones can increase the amount of stress on nearby joints, which can cause osteoarthritis.

&nbsp;

<ul>
	<li>
	<h5>Neurological&nbsp;Problems</h5>
	</li>
</ul>

If Paget&#39;s disease of bone is associated with a bone where a nerve is passing through, like the spine or skull, the remodeling of bone can lead to nerve compression and damage, which in turn causes pain, weakness, or tingling in an arm or leg and even hearing loss.

&nbsp;

<ul>
	<li>
	<h5>Heart&nbsp;Failure</h5>
	</li>
</ul>

In severe cases of PDB, your heart may also get involved as it will have to work much harder to pump blood to the influenced bones. This increased workload may cause heart failure.

&nbsp;

<ul>
	<li>
	<h5>Bone&nbsp;Cancer</h5>
	</li>
</ul>

Bone cancer can occur in up to 1% of the people who have Paget&#39;s disease of bone.

<div>&nbsp;</div>

Risk factors are the parameters that increase your risk of getting a disease. Risk factors for PDB include<a href="#accordion">[5]</a>:

&nbsp;

<ul>
	<li>
	<h5>Age</h5>
	</li>
</ul>

People who are older than 50 years of age are most likely to develop PDB.

&nbsp;

<ul>
	<li>
	<h5>Sex</h5>
	</li>
</ul>

PDB has a predilection towards men compared to women.

&nbsp;

<ul>
	<li>
	<h5>Origin</h5>
	</li>
</ul>

Paget&#39;s disease of bone is more prevalent in England, Scotland, central Europe, and Greece.

&nbsp;

<ul>
	<li>
	<h5>Family&nbsp;History</h5>
	</li>
</ul>

Having a family history of any disease can increase your risk too, similar is the case with PDB.

<div>&nbsp;</div>

Paget&rsquo;s disease is considered inevitable for most people with risk factors. However, an exercise routine may help to maintain your skeletal integrity. Furthermore, you should avoid gaining weight so that it can relieve some pressure off of your joints and bones. 
&nbsp;

Naturally, the genetic makeup of PDB is complicated, as it is made from rare mutations in the SQSTM1 gene and small effects found in other genes. Recent studies show that mutations in SQSTM1 cause autosomal dominant (AD) PDB with high penetrance. It also accounts for up to 40% of familial PDB cases and 10% of apparently sporadic PDB diagnoses. Moreover, it was also found that the common non-SQSTM1 PDB variant is hypothesized to contribute to the disease. It does so by interacting with SQSTM1 mutations and ultimately influencing disease severity<a href="#accordion">[6]</a>. 
&nbsp;

Key Points

<ul>
	<li>Paget&#39;s disease of bone (PDB), is also known as osteitis deformans and refers to a localized skeletal disorder that may involve either a single bone or multiple bones.</li>
	<li>DB has proven to be the second most common type of bone disease. The bone disorder involves remodeling of the bone i.e. its structural integrity becomes compromised and the outlook of the bone changes.</li>
	<li>The disease is prevalent in around 1&ndash;2% of white adults aged older than 55 years.</li>
	<li>A study done on the archaeological skeletons of Northern England origin, found a prevalence of 2.1% in people older than 40 years of age.</li>
	<li>According to a survey, PDB is rare to establish under 25 years of age and not usually seen before 40 years.</li>
	<li>The disease is mostly seen in the United Kingdom and Western Europe. However, is also common in people who migrate to Australia, New Zealand, South Africa, and South America from Britain.</li>
	<li>The primary lesion in the PDB is an increase in osteoclastic activity which causes bone resorption, or the breaking down of the bone</li>
	<li>Following bone resorption, the osteoblasts cause bone formation.</li>
	<li>As a result, the bone shows a mosaic of woven and lamellar bone that has poor mechanical integrity and increases the patient&rsquo;s risk for fracture and deformity.</li>
	<li>PDB is seen to commonly affect the pelvis and spine, in particular, the lumbar spine.</li>
	<li>While monostotic refers to the involvement of a single bone, polyostotic refers to the involvement of multiple bones.</li>
	<li>If your pelvis is involved, you may complain of hip pain.</li>
	<li>Skull involvement can lead to hearing loss or headaches.</li>
	<li>If a patient has his or her spine involved, the nerves can compress which may ultimately lead to pain, tingling sensation, and numbness in an arm or leg, depending on which nerve is compromised.</li>
	<li>Due to the loss of structural integrity, enlarged bones of your legs put unnecessary stress on the adjacent joints as well, leading to <a href="https://www.merisehat.pk/disease/osteoarthritis-64627" target="_blank">osteoarthritis </a>of the knee or hip.</li>
	<li>Researchers have not concluded what exactly causes Paget&rsquo;s disease, but it is believed that the genes passed on through families might play a crucial part.</li>
	<li>Although there are no specific tests to screen a person for Paget&rsquo;s disease of the bone, a detailed history of the parents along with the relevant signs and symptoms presented by the patient can warrant diagnostic tests to be carried out.</li>
	<li>High ALP levels are considered one of the earliest signs of Paget&rsquo;s disease.</li>
	<li>With X-ray images, your doctor aims to assess if your bones are under the influence of Paget&rsquo;s disease.</li>
	<li>Your healthcare provider may use a bone scan to see which of the bones are affected and to assess its severity.</li>
	<li>Paget&rsquo;s disease of the bone can be tackled by medicines as well as by surgical intervention.&nbsp;</li>
	<li>Commonly osteoporosis drugs such as bisphosphonates, like alendronate are mostly used for the treatment of Paget&#39;s disease of bone.</li>
	<li>Side effects of bisphosphonates should be discussed with your doctor as it can sometimes cause severe muscle, joint, or bone pain, which may persist even when the medication is discontinued.</li>
	<li>Surgical intervention is rarely needed and is only indicated under special circumstances. Some of these situations include the healing of a fracture or the realignment of deformed bones.</li>
	<li>Paget&#39;s disease of bone is considered a slow-progressing disease. However, if not managed effectively, it may cause complications like fractures and deformities, bone cancer, osteoarthritis, and heart failure.</li>
	<li>Risk Factors include age, sex, family history, and place of origin.</li>
	<li>Paget&rsquo;s disease is considered inevitable for most people with risk factors. However, an exercise routine may help to maintain your skeletal integrity.</li>
	<li>Recent studies show that mutations in SQSTM1 cause autosomal dominant (AD) PDB with high penetrance.</li>
	<li>Moreover, it was also found that the common non-SQSTM1 PDB variant is hypothesized to contribute to the disease. It does by interacting with SQSTM1 mutations and ultimately influencing disease severity.</li>
</ul>

<div>&nbsp;</div>

[1] Shaker J. L. (2009). Paget's Disease of Bone: A Review of Epidemiology, Pathophysiology and Management. Therapeutic advances in musculoskeletal disease, 1(2), 107–125.

[2] Mujahed M Alikhan MD. Paget Disease Clinical Presentation. History, Physical Examination, Complications.

[3] Paget's disease of the bone: Symptoms, causes & treatment. Cleveland Clinic.

[4] Paget's disease of bone: Symptoms, causes, and treatment. Medical News Today.

[5] Paget's disease of Bone. Mayo Clinic.

[6] Mullin, B.H., Zhu, K., Brown, S.J. et al. Genetic regulatory mechanisms in human osteoclasts suggest a role for the STMP1 and DCSTAMP genes in Paget’s disease of bone. Sci Rep 9, 1052 (2019).