The Paget's disease of bone , also known as osteitis deformans , Paget's disease , Paget's disease , or Paget's disease referred to, is a disease of the skeletal system, with in one or more areas raised and disorganized bone remodeling, it arrives at the gradually thickening. The spine , pelvis , extremities and skull are mostly affected . It is a chronic , slowly progressive disease that mainly affects the elderly. It can be limited to one bone area ( monostotic ) or affect two or more bone areas ( polyostotic ). At the beginning of the development of the disease there is an increased activity of the osteoclasts , which break down bone substance. Disorderly cultivation processes then follow reactively, with the new bone mass being deformed and brittle. The cause of the disease is unknown. Genetic, viral and environmental influences are discussed.
Osteodystrophia deformans occurs frequently in Europe, America, Australia and New Zealand - mainly people of European origin are affected. In Asia and Africa (with the exception of South Africa), Osteodystrophia deformans is very rare. This distribution pattern points to genetic influences and is consistent with the hypothesis of one or more founder mutations in northwestern Europe.
The disease was first described and named after the pathologist and surgeon James Paget from England in 1877 , 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 affected, men more often than women in general. The disease rarely occurs before the age of 55, but the prevalence increases steadily thereafter. However, only a fraction of these patients are clinically abnormal and require treatment.
Recently, a decrease in the incidence and severity of the manifestation of Paget's disease was observed.
The mechanism by which osteodystrophia deformans develops is unknown. Since paramyxoviral RNA , antigens and nucleocapsids (e.g. measles viruses and canine distemper viruses ) are found in osteoclasts, osteoblasts and osteocytes , a viral influence is assumed. However, the identity of the inclusion bodies in the cell nucleus, which resemble paramyxovirus nucleocapsids, has not yet been conclusively established.
About 15% of all patients have a positive family history and this shows an autosomal dominant inheritance with incomplete penetrance . 40 to 50% of patients with a positive family history have a mutation in the SQSTM1 gene ( Sequestosome 1 , location 5q35), which encodes the p62 protein, which is important for regulating the function of osteoclasts. 5 to 10% of patients with sporadic, non-familial Paget's disease also have an SQSTM1 mutation.
In addition, there are gene mutations in three different genes that cause five rare clinical syndromes of osteoclastic disorders that are similar to Paget's disease:
- Insertion mutations in exon 1 of the TNFRSF11A gene ( tumor necrosis factor receptor superfamily, member 11a, NFKB activator , localization 18q22.1), encoding RANK (also: CD265), with autosomal dominant inheritance, occurring in adolescence with extensive bone lesions, tooth loss and Deafness due to three different diseases:
- Familial expansile osteolysis
- Early onset familial Paget's disease of bone
- Expansive skeletal hyperplasia
- Mutation of the gene TNFRSF11B ( tumor necrosis factor receptor superfamily, member 11b , location 8q24), which encodes the protein osteoprotegerin (formerly OPG), in juvenile Paget's disease with pronounced bone lesions, bone fractures and deformities, deafness and premature cardiovascular diseases autosomal recessive inheritance
- Mutation of the gene VCP ( valosin containing protein , localization 9p13, protein p97) in the context of a syndrome with inclusion body myopathy, Paget's disease and frontotemporal dementia, with autodomal dominant inheritance, occurring in the third to fourth decade of life.
Osteodystrophia deformans usually does not appear until after the age of 55, is often symptom-free and is generally diagnosed during an examination or X-ray because of other symptoms. It starts as an inflammatory process in one or (mostly) several bones and is painful at this point; the scintigraphy shows an increased rate of bone remodeling . X-rays of the bone show blurred areas of light.
As the disease progresses, the inflammation recedes and leaves a dense but irregular sclerosis (lime-rich compression) of the bone, often also deformities, pressure-related bending and swelling of the affected skeletal elements, such as a curvature of the spine, an arched chest and a curvature of the legs. If the bones of the lumbar spine are thickened, sciatic pain can occur that radiates into the leg ( root compression syndrome ).
The disease can be noticed by local bone pain, whereby one can feel the overheating due to the overactivity through the skin. At an advanced stage, the skull can thicken as the head circumference increases. If the cranial nerves are damaged by the bone growth, this can lead to hearing loss (stiffening of the auditory ossicles , overgrowth of the cochlea or pinching of the auditory nerve ) and blindness. In terms of fine tissue, a mosaic-like, coarse-meshed but stable lamellar repair bone is characteristic.
The excessive excretion of calcium can lead to kidney stones , the increased blood flow to the bones promotes heart failure . The excessive division activity of the bone cells leads to the development of a malignant bone tumor in about 1% of cases . If such complications are suspected, computed tomography or magnetic resonance imaging is useful.
The determination of the alkaline phosphatase in the serum is first and foremost for diagnosis and monitoring and is increased in more than 85% of cases in untreated Paget's disease. Released amino acids (especially hydroxyproline ) can be detected in the urine as an expression of increased bone loss . Due to the increased activity of the osteoclasts, there is an increase in blood levels, while the calcium levels in the serum remain normal. Markers that indicate increased bone resorption (breakdown) of type 1 collagen in bone, such as C-terminal telopeptide (CTX), may also be increased.
A biopsy is only useful in doubtful early stages.
Treatment is symptomatic with pain-relieving and anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs , bone relief, physiotherapy and, if necessary, surgical stabilization of bone fractures. If symptoms do not improve, drugs can prevent bone loss and relieve pain; Bisphosphonates and calcitonin inhibit bone loss and can prevent deformities if taken regularly and in good time. Bisphosphonates ( zoledronate , Aclasta ® ; pamidronate, Aredia ® ) have recently become available for intravenous infusion. They replace the daily tablet intake. The single infusion of zoledronate has a duration of action of over a year. In addition, vitamin D and calcium are prescribed. If the hip is particularly severely damaged, a hip replacement may be necessary.
Osteodystrophia deformans in animals and in the fossil record
So far, this disease has only been described in a few mammals - such as orangutans and lemurs . The oldest human bones showing signs of this disease date from the Neolithic . In 2011, German researchers demonstrated the disease in a vertebra of the Jurassic dinosaur Dysalotosaurus . According to the researchers, this is the oldest indirect evidence of a virus infection.
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- Guidelines for the diagnosis and treatment of Paget's disease of the bone . (PDF; 216 kB) Umbrella association of German-speaking osteological societies
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