Fibrous dysplasia of bone

Fibrous dysplasia is a chronic deformity of the bone in which the bone will not grow in its usual cellular structure, but forms tumor-like growths of irregular cell structure. This is, as with all of skeletal dysplasia a disorder of the bone tissue, that is a tissue defect. An alternative name is Crohn Jaffe Lichtenstein. In conjunction with visible hormonal disorders ( prematurity, pigmentation of the skin) and strong deformations of the jaw is commonly known as McCune -Albright syndrome.

Definition

Fibrous dysplasia is a rare disease of the human skeletal system. It is the most common bone deformity that occurs in childhood and adolescence. However, there are also diseases in adulthood. In fibrous dysplasia is a chronic disorder in the structure of new bone mass (disturbance of osteoblast differentiation). Instead structured and mineralized new bone in the connective tissue -like, fibrous bone tissue is formed, in which the fibrous bone cells are not aligned. This leads to an expansion of the bone and increased fracture risk.

A distinction forms of fibrous dysplasia, the only one affected bone ( monostotic ) and shapes that several bones affected ( polyostotic ). Although several of bone fibrous dysplasia may be affected at the same time, it is not a disease that spreads from one bone to another, or "infected" adjacent bone.

Fibrous dysplasia can occur in all bones. The commonly affected bones are:

• Skull and facial bones
• Femur
• Shin
• Humerus
• Ribs
• Hip

Symptoms / problems

Affected bones grow and develop irregular deformations, which are caused by the excessive fibrous tissue proliferation. While it increases the volume of the bone, but results in the loss of the stabilizing internal structure ( cancellous ) to structural weakening and thus stress pain and increased risk of fracture.

In addition to frequent bone fractures, a fibrous dysplasia also expressed in a disturbance of hormones ( such as excess growth hormone ), thus suffering from fibrous dysplasia adolescents often an accelerated maturation process can be observed. It can also pigmentation of the skin ( " cafe -au -lait spots " ) or large deformations of the jaw bone ( cherubism ), coupled with the already mentioned hormonal disorders ( Cushing's syndrome, McCune -Albright syndrome ) can occur. A "simple" ( and usually monostotic, but also polyostotic ) Fibrous dysplasia is sometimes referred to by its explorers as Jaffe - Lichtenstein syndrome. However, it is in fibrous dysplasia, McCune - Albright syndrome and also Jaffé - Lichtenstein syndrome to the same causative disease.

Rarely, a fibrous dysplasia together with myxomas of skeletal muscle ( Mazabraud syndrome) or malfunction of the heart, liver, pancreas, thyroid or other organs may occur.

Due to the increased bone remodeling process, a fibrous dysplasia is often associated with an increased value of the alkaline phosphatase in the blood as well as hydroxyproline and deoxypyridinoline in urine ( but what turned not equal necessarily mean a disease of fibrous dysplasia ), which is why these values ​​are examined regularly in those affected should be to determine changes in the activity of fibrous dysplasia.

Because fibrous dysplasia is very strongly associated with hormonal and other cellular metabolic processes, a fibrous dysplasia can stop after puberty. Hormone preparations (such as the pill ) or pregnancy can have a positive or negative influence on the development of fibrous dysplasia.

If fibrous dysplasia of bone on, through the nerve or blood vessels, such as in the spine or the skull bone, there is a danger that these nerves or vessels are clamped.

Although there are some significant physical limitations Fibrous dysplasia patients ( eg frequent operations or deformations ), but was found in a study that in all important areas of life, such as social relationships, education and career, quality of life is completely normal. In contrast, parents of children who are diagnosed with fibrous dysplasia suffer, often very severely from the disease. It is therefore important to educate parents about the disease and to insure that life expectancy as well as social and emotional health of children is not affected.

Causes

Fibrous dysplasia is caused by a mutation of the G- protein nichtvererbbare ( in α - subunit). The mutation is located in the GNAS gene (or Gsα gene) of the 20th chromosome. G proteins are extremely important for signal transduction in the cell metabolism. The mutation results in an over- activation of the enzyme adenylyl cyclase, which controls the catalysis of ATP to cAMP (which is then the actual signal transmission process). cAMP regulates, for example, the heart rate, relaxation of smooth muscle, the effects of numerous hormones and, indeed, the bone cells responsible for building bone (osteoblasts ). The reason for this mutation is unknown. You may already occur in the fetal stage of pregnancy ( then experience the symptoms in childhood and adolescence on ) or only later, after the birth. Because fibrous dysplasia is very strongly associated with hormonal and other cellular metabolic processes, a fibrous dysplasia can stop after puberty. Hormone preparations (such as the pill ) or pregnancy can have a positive or negative influence on the development of fibrous dysplasia.

The gene defect affects only cells in the body, not the germ cells (the first is what we call somatic mutation, whereas gametic mutation in germ cells ). That is, the genetic defect can not be passed on to offspring. Find the mutation that causes fibrous dysplasia, during early embryonic development in the cell mass instead, it will probably come to the McCune -Albright syndrome; Mutation at a later stage of embryonic development of the dissolved probably polyostotic fibrous dysplasia. And a mutation after birth ( in childhood or even adulthood) is blamed for the monostoische fibrous dysplasia. Depending on where the mutation in the cell mass during embryonic development takes place, it is later in said body regions, the disease.

The germ cells arise from primordial germ cells that are already separated from the blood cells during embryonic growth (and are then stored in the gonad ). The inheritance of fibrous dysplasia is therefore almost impossible.

Diagnosis

Fibrous dysplasia of bone affected areas have a characteristic ground glass appearance and clearly limited in the X-ray or CT. When in doubt, bring a biopsy and consideration of a bone sample under a microscope certainty.

The differential diagnosis among other Osteitis deformans ( Paget's disease ) and rickets in question.

Treatment methods

Fibrous dysplasia is often only symptomatic treatment, ie by

• Pharmacological pain relief
• Stabilization and reinforcement of an affected bone
• Threatened removal of bone material, which restricts the movement, pinch nerves or blood vessels
• Removal of bone deformities for cosmetic reasons.

Drug treatment which stops the bone deformity effective, has not yet been found, however, bisphosphonates have proven to slow the fibrous dysplasia and pain relief. There are different classes of bisphosphonates that limit all the action of bone resorbing cells ( osteoclasts), and thus delay the fibrous dysplasia and can also relieve pain. Most often find pamidronate, zoledronate Risedronate and application.