Fibrous dysplasia

Classification according to ICD-10
M85.0	Fibrous dysplasia
ICD-10 online (WHO version 2019)

The Fibrous dysplasia (FD) is a congenital disorder of ossification . Due to the inferior substantia compacta , the bone is distended, deformed and prone to breakage. Another name for (polyostotic) FD is Jaffé-Lichtenstein's disease . Fibrous dysplasia also occurs in the context of McCune-Albright syndrome (in connection with precocious puberty and pigment disorders ). Albright's patient died in 1940 at the age of 10. On July 28, 1922 , Weil reported to the Silesian Society for Patriotic Culture about a 9-year-old girl with premature puberty, brittle bones and dermal pigmentation.

nature

" A benign condition presumably developmental in nature, characterized by the presence of fibrous connective tissue with a characteristic whorled pattern and containing trabeculae of immature non-lamellar bone ."

- World Health Organization definition

It is important to distinguish between polyostotic and monostotic forms. The typical involvement of several or all bones is a serious and incurable disease. In contrast, the individual infestation is usually an incidental finding in adults; one can wait or curette .

Symptoms and Comorbidities

Fibrous dysplasia of the zygomatic bone (marked). Corresponding T2-weighted magnetic resonance imaging (left) and CT (right) of the same patient.

FD can be associated with myxomas of the skeletal muscles ( Mazabraud's syndrome ) or dysfunction of the heart , liver , pancreas , thyroid, or other organs.

Due to the increased bone remodeling process, FD is often associated with an increased level of alkaline phosphatase in the blood and hydroxyproline or deoxypyridinoline in the urine. Controls allow a certain assessment of the course of the FD.

causes

Complex of the G _s protein (2GVD). The α-section, which is changed in an FD, is at the bottom right.

FD is triggered by a non-heritable mutation of the G protein (in the α-subunit). The mutation is in the GNAS gene (or G _s α gene) on the 20th chromosome . G proteins are extremely important in the metabolism of cells for signal transmission. The mutation leads to an overactivation of the enzyme adenylyl cyclase , which controls the catalysis of ATP to cAMP (this is then the actual signal transmission process). cAMP regulates e.g. B. the heart rate, relaxation of the smooth muscles , the effect of numerous hormones and also the bone cells that are responsible for building bones ( osteoblasts ). The reason for this mutation is still unknown. It can occur in the fetal stage during pregnancy (in which case the symptoms appear in childhood and adolescence) or later, after birth. Since FD is very closely linked to hormonal and other cell metabolic processes, it can stop after puberty. This does not change anything about the deformities that have occurred.

The genetic defect only affects somatic cells, not the germ cells (the first is called somatic mutation , whereas with germ cells, gametic mutation ). This means that the genetic defect cannot be passed on to the offspring. If the causative mutation takes place in the cell mass during early embryonic development, McCune-Albright syndrome is likely to occur; Mutation at a later point in embryonic development probably triggers polyostotic FD. And a mutation after birth (in childhood or even adulthood) is held responsible for the monostotic FD. Depending on where the mutation takes place in the cell mass during embryonic development, the disease later occurs in these parts of the body.

diagnosis

Fibrous dysplasia in the heel bone in a patient with known polyostotic fibrous dysplasia. Typical representation in the X-ray image with milky, structureless compression.

The polyostotic FD can be recognized clinically and radiologically at first glance. The affected bone areas show a characteristic, frosted glass-like and indistinctly delimited appearance on X-rays or CT . A biopsy is unnecessary and increases the risk of breakage.

treatment

Bisphosphonates ( risedronate , zoledronate ) inhibit the osteoclasts , but, like operations, do not treat the causal cause of the disease. Interventions on the axial skeleton, such as axial corrections and stabilization with intramedullary nails, involve some risks. If the skull bone is affected, the protective function of the same can be impaired. A neurosurgical operation with excision of the lesion in the healthy and subsequent reconstruction with synthetic materials (titanium or synthetic material such as PEEK, PMMA) can be a low-risk and promising therapeutic approach contrary to the interventions on the axillary skeleton.