Paget’s disease

Paget’s disease: description

The disease Paget’s disease is named after the British surgeon Sir James Paget (1814 – 1899). The term is synonymous with two clinical pictures. On the one hand, “Paget’s disease” signifies a bone disease and, on the other hand, a disease of the breast. In the following, however, only the Paget’s disease of the bones will be treated.

Paget’s disease usually begins after the age of 40 and is the second most common bone disease after osteoporosis. About one to two percent of over-40s in Western Europe are affected by the disease. It is most common in England but is very rare among Asians and Africans. It affects more men than women.

Only about 30 percent of Paget’s cases are diagnosed while alive – so there are a significant number of undiagnosed patients. Only one in 25,000 inhabitants needs a therapy.

Paget’s disease: symptoms

Only ten percent of Paget’s sufferers show symptoms such as local pain, while 90 percent are symptom free. The disease is therefore not diagnosed in most cases.

Paget’s disease: bone, joint and muscle pain

The reduced bone stability and deformation in Paget’s disease lead to painful tears and fractures in the bones. The patients complain of bone pain. In addition, the altered bone statics can cause stress levels with muscle tension and stubborn muscle pain.

As Paget’s disease progresses, malocclusions develop as a result of bone fractures. Often, extreme deformations of the affected bones, which are also visible from the outside, can occur. For example, curved and thereby shortened shins (“sheath-shin”) or an enlarged head circumference are typical. The affected woman often no longer fits her hat.

The adjacent joints can form so-called secondary arthrosis due to the deformities: The deformed bone overloads the joints excessively, causing them to wear out.

Paget’s disease: overheating

Paget’s disease stimulates bone metabolism. This creates new blood vessels that lead to increased blood flow. The vessels expand and ignite. If the bone lies directly under the skin, for example on the tibia, the increased blood flow can be felt as overheating.

Paget’s disease: nerve compression

Uncontrolled bone formation in Paget’s disease can also damage nerves. For example, as the size of the skull increases, nerves or even brain tissue can be compressed.

Paget’s disease: deafness

If nerves are affected in the area of ​​the skull, deafness occurs in 30 to 50 percent of cases. Reason are sensory disturbances of sound and rare conduction disturbances, which are due to bony joint bridging of the ear bones or a compression of the Hörnerven.

Paget’s disease: malignant tumors

Malignant tumors occur in less than one percent of Paget’s disease patients with symptoms. Bones affected by the disease develop an osteosarcoma – a malignant bone tumor commonly referred to as bone cancer. Pelvic, femoral and humeral bones are mainly affected. The affected patients notice that the symptoms suddenly worsen and the deformation of the bone increases. An increase in alkaline phosphatase (a liver enzyme) can be detected in the blood.

Paget’s disease: causes and risk factors

Bones are not static structures, but are constantly being rebuilt. Two different types of cells are involved in this: osteoclasts break down bone, while osteoblasts break it down. In a healthy person, this process is coordinated – bone formation and degradation are in balance.

Paget’s disease: disturbed balance

In contrast to healthy bone, this process of bone formation and degradation in Paget’s disease is not uniform and coordinated, but without any system and regional differences. This is due to pathologically altered osteoclasts. The altered bone areas contain so-called giant osteoclasts – they have up to a hundred cell nuclei, while a normal osteoclast has only three to 20 cell nuclei. These osteoclasts are significantly more active than the healthy variants and therefore break down more bone substance.

In response, the body of Paget’s disease patient seeks to form new bone material. For example, zones with firmer bones lie next to those with a reduced content of bone calcium salt. The bone changes its shape, looks distended, thickened or deformed or breaks faster in places with reduced lime content. The remodeling processes particularly affect bones that are heavily stressed. These include pelvis (in about two thirds of Paget’s sufferers), thighs, tibia, cranial bones (by chewing activity) and lumbar spine.

It is not known exactly why these giant osteoclasts form in Paget’s disease. It is thought that a genetic predisposition plays a role in this. Experts also discuss whether infection with certain viruses (slow virus infection) is involved in the development of Paget’s disease. With the electron microscope, inclusions are found in the nuclei of the giant osteoclasts, which are reminiscent of viruses, on the affected areas. These inclusions are found only in Paget osteoclasts but not in any other bone cells.

Paget’s disease: examinations and diagnosis

People with Paget’s disease are not always looking for a doctor because of their condition. Often, the disease is also discovered by accident, such as changes in blood levels or in the radiograph. The right contact person for suspected Paget’s disease is the specialist in internal medicine and endocrinology. It can be visited but first of all the family doctor, who may cause further investigations if necessary.

Paget’s disease: medical history

First, the doctor will raise the medical history (anamnesis). Because even based on the symptoms that the person described, the doctor can estimate approximately whether the disease Paget’s disease comes into question as a cause. He may ask the following questions during the anamnesis:

• Do you have pain? Where does this pain occur?
• Is the pain localized in a specific location, for example, on the back, head or joints?
• How long have this pain been?
• Have you noticed an increased skin temperature over the affected areas?
• Has your head circumference changed or increased? Does your hat still fit you?
• Do you have any other complaints such as paralysis, sensory, visual or hearing problems?

Paget’s disease: physical examination

After collecting the medical history, the doctor will briefly examine you. He carefully scans the affected areas to get an impression of the pain intensity. He will also check for malpositions such as deformities, contractures or shortening. In the side comparison (right and left side of the body), the doctor sees whether muscle has regressed. He will also ask you to run along a line to judge if the gait pattern is fluid or limping. He will also perform some functional tests on the joints and range of motion.

If necessary, a few neurological examinations are necessary to test whether the spinal canal is narrowed or the spinal cord is compressed.

Paget’s disease: laboratory examination

A blood test usually shows an increased concentration of the enzyme alkaline phosphatase (AP) in people with Paget’s disease. This is an indication of an increased activity of the osteoblasts, ie the bone-building cells.

The activity of the osteoclasts, the bone-degrading cells, can also be determined by measuring the amount of the amino acid hydroxyproline in the urine.

Paget’s disease: X-ray

To safely diagnose Paget’s disease, an X-ray examination is necessary. It is usually performed only on the bony areas with complaints. The course of Paget’s disease is divided into three phases, which are visible in the X-ray. However, they can also be simultaneously detectable in a patient:

• In the first phase, bone resorption is visible (osteolysis).
• In the second and most frequent phase, a mixed picture of areas with bone loss and areas with hardened bone material is visible (osteosclerosis).
• In the third phase predominantly indurations with distention and deformities of the affected bones can be seen. The trabecular system (cancellous bone) shows coarsened and is interspersed by individual bone-dissolving foci.

Paget’s disease: scintigraphy

To search for further bone lesions, a bone scintigraphy is performed – a nuclear medical examination, with which up to 50 percent more affected bone areas can be discovered than with the X-ray examination. The patient is given a radioactively labeled substance in the bloodstream. The substance settles in the bone, especially where it has a high metabolic activity and is particularly well supplied with blood. In a subsequent X-ray, the accumulation of the substance in the bone and thus areas with increased bone remodeling can be detected.

Paget’s disease: computed tomography or magnetic resonance tomography

Depending on the medical history and the results of the physical examination and the laboratory tests further equipment investigations follow. To clarify whether the spine is affected by Paget’s disease, computed tomography (CT) or magnetic resonance tomography (MRI) can be used.

Paget’s disease: bone biopsy

Due to the typical changes in the X-ray image and the striking laboratory values, the diagnosis “Paget’s disease” is usually unambiguous. In case of doubt, however, a bone biopsy (removal and examination of a tissue sample of affected bones) can be performed to ensure the diagnosis. In addition, other bone diseases can be differentiated from the Paget’s disease and a possible malignant bone tumor can be ruled out.

Paget’s disease: treatment

The goals of Paget’s treatment are, on the one hand, the alleviation of pain and, on the other hand, the arrest of bone remodeling and thus the spread of Paget’s disease. To achieve these goals, bisphosphonates are used as the drug of choice in the treatment of Paget’s disease. In some cases, calcitonin is also given. Both groups of active substances inhibit the increased bone metabolism and thus, above all, the excess bone breakdown by the osteoclasts. Deformations and fractures of the bones can thus be avoided. In addition, other therapeutic measures are used in Paget’s disease.

Paget’s disease: bisphosphonates

Bisphosphonates are either taken as oral medications (such as risedronic acid) or given as infusions (such as pamidronic acid and zoledronic acid).

In tablet form, however, the intestine absorbs the active ingredients only poorly. Therefore, they must be taken on an empty stomach with a large glass of water. In order not to hinder the intake in the intestine, you should then eat for about an hour nothing. In about two to ten percent of patients with Paget’s disease, side effects such as nausea, abdominal pain, vomiting or diarrhea occur when oral bisphosphonates are used. This can be prevented if bisphosphonates are given as an infusion.

The treatment of Paget’s disease with bisphosphonates takes place in cycles. The tablets are taken daily or once a week for a period of two to six months. The infusion duration is between 15 minutes and four hours, depending on the substance. The infusions are administered either at intervals of four weeks to three months or as a brief infusion once a year. The latter applies to the bisphosphonate zoledronate.

Paget’s disease: calcitonin

Alternatively, Paget’s disease can be treated with the hormone calcitonin, which also inhibits the activity of osteoclasts. However, it seems less effective than bisphosphonates.

Patients receive calcitonin either in the form of a syringe or over the nose using a nasal spray. Oral use is not possible because the stomach acid would destroy the hormone. Calcitonin causes in a relatively large number of patients to side effects and intolerance reactions, especially redness, but also to nausea and vomiting.

Paget’s disease: pain therapy and surgical therapy

Patients with Paget’s disease who suffer from persistent pain, bone deformities, fractures and secondary arthrosis, especially in the legs, may require the use of analgesics and surgical treatment.

Acetaminophen is the drug of first choice in pain therapy. With physical measures such as physiotherapy, massage, electrical and balneotherapy as well as with local injections can also be achieved an alleviation of symptoms. It is not recommended to use heat because the bones are already overheated in Paget’s disease.

For femoral fractures and advanced arthrosis of the hip and knee joints surgery may be useful. If neurological symptoms such as paralysis or gait disturbances occur due to nerve compression due to bone deformation in the area of ​​the spinal canal, spinal surgery must be performed.

Paget’s disease: other therapeutic measures

In addition, adequate calcium and vitamin D intake should be considered as they play an important role in bone metabolism. Calcium should be taken at a time interval of two hours to bisphosphonates, otherwise their absorption worsens.

Paget’s disease: disease course and prognosis

In patients with Paget’s disease, the risk of developing a malignant bone tumor (osteosarcoma) is increased. Regular medical checks are therefore a must for Paget’s disease. For follow-up, blood levels of alkaline phosphatase (AP) should be determined three months after initiating therapy and every six months thereafter. If pain occurs again, X-ray should be taken if necessary to rule out other possible conditions.

The prognosis for Paget’s disease is good, but it also depends on how severe the disease is. In some patients, only a limited area of ​​the bone is affected. In about one percent of cases, bone cancer (Paget’s sarcoma) develops. In this case, surgery is required as early as possible.

Despite the more or less severe physical limitations, life expectancy is at Paget’s disease usually not shortened.