Paget's disease symptoms, causes and treatment

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Anthony Golden

The Paget's disease, Also called osteitis deformans, it is a chronic disorder that affects the bones. It is characterized by an exaggerated growth of the bones, and a disorganized remodeling of these. This condition leads to weak bones and fractures, and is the second most common bone disorder in the mature population (after osteoporosis)..

The exact causes of this disease are not fully known. It has been observed that Paget's disease is repeated in the same family, so there are surely genetic components in its origin.

Source: nejm.org

Genetic factors seem to combine with other environmental factors, causing a pathological increase in the activity of osteoclasts, cells that disintegrate, reabsorb and remodel bones..

This disease manifests itself after several years of evolution, and causes bone deformities, fractures and wear in cartilage. Any bone can be affected, although they usually involve the pelvis, femur, tibia, spine, or skull. The most affected area is the lumbar spine (between 30% and 75% of cases).

Other less frequent clinical manifestations that this condition carries are compression neuropathy and sensorineural deafness (hearing loss due to damage to the internal ossicles of the ear). Heart failure and even osteosarcoma (malignant bone cancer) can also appear.

James Paget described this disease in detail in 1877, in an article titled "On a form of chronic inflammation of bones (osteitis deformans)".

At first it was called osteitis deformans because it was considered a chronic inflammation of the bone. It is currently known to be a chronic bone modeling disorder, but without the existence of inflammation, which is why it has been pointed out that the appropriate term is "deforming osteodystrophy".

This disease should not be confused with other diseases named after this doctor, such as extramammary Paget's disease or Paget's disease of the breast..

Article index

  • 1 Prevalence of Paget's disease
  • 2 Causes
    • 2.1 Genetics
    • 2.2 Environment
  • 3 Symptoms
  • 4 Diagnosis
  • 5 Treatments
    • 5.1 Pharmacological
    • 5.2 Orthosis
  • 6 References

Prevalence of Paget's disease

Paget's disease is more common in men than women, and it tends to appear in people over 55 years of age. The incidence increases with age, in fact, in people over 80 years of age it is approximately 10%.

Its prevalence seems to vary greatly from place to place in the world. It appears mainly in Europe, North America, New Zealand and Australia. While it is very rare in Asian countries.

In countries with a high prevalence there is a downward trend in Paget's disease, approaching 3%. In Spain, France, Italy and part of the United States, the prevalence is intermediate, between 1.5% and 2.5%. In Scandinavian countries, as well as in Africa, Asia and South America, the prevalence is less than 1%.

Furthermore, prevalence is difficult to determine because it appears to vary even within the same country. Thus, in some cities in England the prevalence is 2% of the population. In contrast, in Lancaster, the prevalence is 8.3%.

Causes

The exact cause of Paget's disease is unknown. What is known is that it is associated with an abnormality of osteoclasts, the cells that produce bone formation and its resorption..

Specifically, these cells are overactive, causing certain bone areas to break down and then be replaced by a new area of ​​abnormal bone. This new portion is larger, but more prone to fractures.

Genetics

There are studies that indicate that there may be an autosomal dominant inheritance. This means that a single copy of the altered gene would already cause the disease in the offspring..

Thus, Paget's disease is linked to specific genetic mutations. The one that has been studied the most is that of the sequestoma-1 gene (SQSTM1)..

Atmosphere

In addition to hereditary components, environmental factors also appear to play a role. For example, paramyxovirus infection, drinking untreated milk and water, and vitamin D deficiency.

In a study carried out in a high prevalence focus (in an area of ​​Madrid) it was concluded that the cause was the consumption of bovine meat without sanitary control. This conclusion includes infectious contagion in childhood, when health controls did not exist or were scarce..

Thus, the ingestion of an infectious agent from animal tissues could cause diseases, such as Creutzfeldt-Jakob, and of course, Paget's disease..

On the other hand, in the Lancashire (England) focus, Paget's disease was related to the consumption of arsenic from pesticides. However, these studies do not have strong evidence to show the cause..

Currently, the disease is less frequent due to changes in ethnic composition due to migration and improved hygienic conditions. Its severity has also been reduced since the discovery of osteoclast agents that counteract bone hyperactivity.

Symptoms

Between 70-90% of patients with Paget's disease do not experience any symptoms, at least initially. Obviously, the clinical manifestations will depend on the location and number of the lesions, as well as the involvement or not of the joints. These patients generally experience:

- Pains in the bones This pain is constant, dull, deep, and may increase at night..

- Non-specific headaches.

- Joint pain as a result of cartilage injuries.

- Increase in calcium levels in the blood.

- Bony deformations such as bowing of the tibia, which causes the affected bone to arch in the form of a “parenthesis”. Legs (or other areas) may be bowed and deformed.

- Deformation of the skull or face, with an increase in the size of the head.

- Elevated skin temperature in affected bone areas.

-  Vasodilation in the areas involved.

- Neurological complications can occur as a consequence of poor circulation of cerebrospinal fluid in case of skull involvement. Some of them are hydrocephalus, mental disorders and even dementia. Hearing loss (decreased hearing) or tinnitus (hearing noises that are not present) may also occur.

-Deafness can occur in 30-50% of cases. Although this is not exactly known if it is caused by Paget's disease or gradual age-related hearing loss (presbycusis).

-When the bones of the face are affected, loosening of the teeth or problems with chewing can occur.

- Compressions on the spinal cord. As a consequence, this can lead to progressive pain, paresthesia, gait problems, or bowel or bladder incontinence..

- Associated conditions such as arthritis can also occur. Since, for example, the inclination of the long bones of the legs can put pressure on the joints.

- People affected by Paget's disease may develop kidney stones.

- Calcification of collagen or other pathological deposits may also occur.

- As mentioned, pressure on the brain, spinal cord or nerves can cause problems in the nervous system..

- In more advanced cases, cardiovascular diseases can appear. In addition, the abnormal bone tissues that are formed have pathological arteriovenous connections. This generates a greater activity of the heart to be able to supply oxygen to the bones.

- A rare but life-threatening complication is osteosarcoma. It is a bone neoplasm (bone cancer) that is manifested by increased pain in the area, soft bone enlargement and injuries.

Diagnosis

The diagnosis of Paget's disease is made through the radiological examination of the skeleton.

In the early stages of the disease, osteolytic lesions appear in the affected bone. These injuries occur when certain parts of the bones begin to dissolve, forming small holes. The pathological process progresses at a rate of 1 centimeter per year.

In the next stage of the disease there are sclerotic lesions, which cause a pathological formation of the new bone. Can be seen on radiographs (along with osteolytics).

In the last stage of the disease, the sclerotic lesion predominates and there is an increase in bone size. If the disease is not detected by the radiological finding, professionals can resort to a bone biopsy as the definitive method.

Paget's disease can also be detected with a bone scan, performed with a radiolabeled bisphosphonate. This method detects the areas with the highest blood flow and bone function, which indicates a fundamental characteristic of the disease. In addition, it is useful to establish the extent of the affectation.

People with Paget's disease often have high levels of alkaline phosphatase and calcium in the blood. In addition to high levels of pyridinoline (fragments derived from bone tissue and cartilage), and hydroxyproline in the urine.

Treatments

Not all patients affected by Paget's disease require specific treatment. Most of them are elderly and have small, localized bone lesions in parts that have a low risk of complication.

The goal of treatment is to remit the biochemical process to restore normal bone metabolism as well as reduce pain. It also seeks to avoid complications such as malformations, the appearance of osteoarthritis, fractures and compression of nerve structures.

Pharmacological

Pharmacological treatment is indicated when the disease is extensive or very active. Antiresorptive drugs are currently used to reduce the high bone turnover and osteoclast activity.

Bisphosphonates

Bisphosphonates, a medication that reduces bone turnover and fractures, are also prescribed. The bisphosphonates approved for the treatment of Paget's disease in Spain are pamidronate, risedronate and zoledronic acid (amino acids)..

From the non-amino group, etidronate and tiludronate. There are other bisphosphonates that have shown efficacy for the treatment of this disease but are not authorized in some countries (such as Spain). They are alendronate, ibandronate, neridronate, olpadronate, and clodronate..

Drug treatment can also help the patient prepare for orthopedic surgery. Since they reduce intraoperative bleeding and control hypercalcemia by immobilization.

Calcitonin

When bisphosphonates cannot be used, calcitonin is used. It is a peptide hormone with the ability to inhibit bone resorption. Gallium nitrate can also be used for bisphosphonate resistant patients.

If the patient follows a treatment with this type of drug, it is necessary to use calcium and vitamin D supplements. The objective is to avoid hypocalcemia and / or secondary hyperparathyroidism.

Anti-inflammatories

The main symptom of this disease is pain, derived from complications and injuries. To treat it, non-steroidal anti-inflammatory drugs and pain relievers are used. In some cases, tricyclic antidepressants may be prescribed..

Orthosis

Orthotic treatment (appliances, devices or splints to facilitate movement) may also be necessary, as well as hearing devices, canes and others that help the patient live with a better quality of life.

Occasionally, surgical treatment must be used. This is carried out when there are deformities that cause great pain or bone fissures. If pagetic arthropathy (venous circuits in the bone) occurs, an arthroplasty may be necessary.

Patients with Paget's disease must receive sufficient sunlight and adequate physical exercise to maintain good bone health. Professionals must create an exercise program suitable for each person to prevent the symptoms of this disease from worsening and to maintain functionality. It is also advised to maintain a healthy body weight.

References

  1. Audran, M., Sutter, B., & Chappard, D. (2016). Paget's disease of bone. EMC-Locomotor Apparatus, 49 (1), 1-16.
  2. Cuesta, J. C., Gadea, J. B., Pérez, A. G., Le Quément, C. M., & Heredia, E. S. Chapter 25: Paget's disease of the bone. Rheumatic diseases: SVR update. University Clinical Hospital, San Juan. Alicante.
  3. Lyles K.W., Siris E.S., Singer F.R. And Meunier P.J. (2001). Guidelines for the diagnosis and treatment of paget's disease of bone. Rev Esp Enferm Metab Hosea, 10 (1): 28-34.
  4. Menéndez-Bueyes, L. R., & Fernández, M. D. C. S. (2016). Paget's disease of bone: an approach to its historical origins. Clinical Rheumatology.
  5. Oliveira, L. L., & Eslava, A. T. (2012). Treatment of Paget's disease of bone. Clinical Rheumatology, 8 (4), 220-224.
  6. Paget Disease. (2016, November 21). Retrieved from MayoClinic: emedicine.medscape.com.
  7. What Is Paget's Disease of Bone? (November 2014). Obtained from NIH Osteoporosis and Related Bone Diseases: niams.nih.gov.

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