Paget's disease of bone

The Osteitis deformans osteitis deformans as, Paget's disease, Paget 's disease or Paget's disease referred to, is a disease of the skeletal system with one or more areas unorganized and increased bone turnover, which is gradually comes to thickening. Mostly affects the spine, pelvis, extremities, and skull. It is a chronic, slowly progressive disease, suffer from the mainly elderly. It may be limited to an area of bone ( monostotic ) or two or more bone areas concern ( polyostotic ). At the beginning of the development of the disease is an increased activity of osteoclasts that break down bone. Reactive follow unordered cultivation operations, the new bone is deformed and brittle. The cause of the disease is unknown, genetic, viral and environmental factors are discussed.

Epidemiology

The Osteitis deformans occurs frequently in Europe, America, Australia and New Zealand - are affected predominantly people of European origin. In Asia and Africa ( with the exception of South Africa ) Osteitis deformans is very rare. This distribution pattern, pointing at genetic influences and is consistent with the hypothesis of one or more founder mutations in northwestern Europe.

First described and named the disease was in 1877, the pathologist and surgeon James Paget from England, where the disease is most common. In Western Europe, up to 5 % of men and 8% of women in the eighth decade of life are concerned, generally men more often than women. Before the age of 55, the disease is rare, but the prevalence increases steadily thereafter. However, only a fraction of these patients is clinically apparent and require treatment.

Finally, a decline in the incidence and severity of the manifestation of Paget's disease was observed.

Etiology

The mechanism of Osteitis deformans is unknown. Since you (eg measles virus and canine distemper virus ) is paramyxovirale RNA, antigens and nucleocapsids in osteoclasts, osteoblasts and osteocytes, one starts from a viral effect. The identity of the inclusion bodies in the nucleus, resembling paramyxovirus nucleocapsids, however, could not yet be clarified beyond doubt.

In approximately 15 % of patients there is a positive family history, and thereby reflects an autosomal dominant inheritance with incomplete penetrance. Of the patients with a positive family history indicate 40 to 50% of a mutation of the gene SQSTM1 ( Sequestosome 1 localization 5q35 ), encoding the protein p62, which is essential for the regulation of the function of osteoclasts. And 5 to 10% of patients with sporadic non- familial Paget's disease have a SQSTM1 mutation.

Moreover, there are mutations in three different genes that cause rare five clinical syndromes osteoclast disorders that are similar to Paget's disease:

• Insertion mutations in exon 1 of the gene TNFRSF11A ( tumor necrosis factor receptor superfamily, member 11a, NFKB activator, location 18q22.1 ), the RANK ( also: CD265 ) encoding and with autosomal dominant inheritance, onset in adolescence with extensive bone lesions, tooth loss numbness in the context of three different diseases: Familial expansile osteolysis
• Early onset familial Paget 's disease of bone
• Expansive Skeletthyperplasie

Pathogenesis

The Osteitis deformans usually occurs only beyond the age of 55 on, often goes without symptoms and is generally used in an investigation or the X-ray detected because of other complaints. It begins as an inflammatory process in one or (usually) several bones and at this time is painful; scintigraphy results in an increased rate of bone turnover. X-rays of the bone show blurred cloudy.

In the course of the inflammation goes back and leaves a dense, but irregular sclerosis ( calcareous compression ) of the bone, and often deformity, pressure-induced bending and swellings of the affected skeletal elements, such as spinal curvature, a curved chest and a curvature of the legs. In a thickening of the bones of the lumbar sciatic pain may occur, which radiate to the leg ( radicular compression syndrome).

The disease can be noticed by local bone pain, which can be felt through the skin, the warmth due to the overactivity. In advanced stages, it can lead to the thickening of the skull with increase in head circumference. Are the cranial nerves damaged by bone growth, for this hearing ( stiffening of the ossicles, clogging of the cochlea or the auditory nerve contusion ) and blindness may result. Histologically, at this time a mosaic- like coarse-mesh but stable lamellar bone repair characteristic.

The excessive excretion of calcium can lead to kidney stones, the increased bone blood flow promotes heart failure. The split excessive activity of bone cells occurs in about 1 % of the cases to the development of a malignant bone tumor. If such complications are suspected, a computed tomography or magnetic resonance tomography is useful.

Diagnosis

Imaging methods

Essential for the diagnosis is the X-ray image in which at an early stage of the disease, osteolysis can be demonstrated. The increased bone remodeling can be detected by bone scintigraphy.

Laboratory tests

The determination of alkaline phosphatase in serum is paramount for the diagnosis and observation and is elevated in about 85% of cases of untreated Paget's disease. As an expression of increased bone resorption liberated amino acids (especially hydroxyproline ) in the urine. Due to the increased activity of osteoclasts is in the blood, an increase in recorded while the calcium levels remain normal in the serum. Markers that indicate an increased bone resorption (breakdown) of type 1 collagen in bone, such as the C-terminal telopeptide (CTX ), may also be increased.

Pathology

Where the studies cited above, the diagnosis remains unclear or is a secondary sarcoma can be excluded, a bone biopsy can be performed.

Therapy

Treatment is symptomatic with pain-relieving and anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs, relief of bone, physiotherapy and, where appropriate operative stabilization of fractures. If there is no improvement in symptoms, medications may be prescribed to prevent the loss of bone mass and reduce pain; Bisphosphonates and calcitonin inhibit bone resorption and may prevent deformities with timely, regular use. Recently, there is also a bisphosphonate ( zoledronate, Aclasta ®) for intravenous infusion available. The one-time infusion has a duration of action of more than one year and replaced daily tablet intake. Vitamin D and calcium supplement may be prescribed. In a particularly severe damage to the hip hip replacement may be required.

Osteitis deformans in animals and in the fossil record

So far, this disease has been described in only a few mammals - as in orangutans and lemurs. The oldest human bones that show signs of the disease, originate from the Neolithic period. In 2011, German researchers reported the disease according to a vertebra of the Jurassic dinosaur Dysalotosaurus. According to researchers, these are the oldest indirect evidence of a viral infection.