CLASSIC PRESENTATION

FD is often asymptomatic. It can be an image discovered accidentally when an X-ray is requested for another reason. When it is symptomatic, FD causes bone pain, deformities, locomotor dysfunction (limitation in mobility of part of a limb, a limp etc), permanent disfigurement and fractural or neurological complications (1). Polyostotic forms are more frequently symptomatic, in particular painful, than isolated lesions. Chronic bone pain often develops, which is generally improved through bisphosphonate therapy (2). Headaches are frequent for those affected in facial or cranial areas, which come and go sporadically. Limb pain can be acute, before a crack is discovered, a warning of a fracture complication.  Deformities are described based on the site they affect: deformities to the rib cage from multiple rib lesions, a shepherd’s crook deformity of the femur, and curvature of the tibia. The most dramatic deformities and the ones that cause most aesthetic damage are the result of the various bones of the skull being affected: bumps on the occipital, parietal or frontal bones, leontiasis ossea as a result of large areas of the face being affected, prognanthism from an affected mandible, and exophthalmia from an affected orbital area. These deformities are also the source of neurosensory complications, the most frequent being diplopia from compression of the oculormotor nerve. Visual and auditory acuity problems, nasal sinus function issues and problems with dental alignment are also possible. The spine being affected rarely leads to nerve root or medullary complications.

ASSOCIATIONS AND SYNDROMES

The mutation affects other cell types than osteoblast precursors, notably skin melanocytes and the cells of many of the endocrine glands (the gonads, the thyroid, the pituitary gland, the adrenal glands, etc.) (3). Characteristic skin lesions seen are pigmentation marks, which can be single or in multiple areas, but in general there are very few, of variable colour, typically of “café-au-lait” type. They are often larger than 2 cm, with irregular edges, “jagged” in appearance, which distinguishes them from pigmentation marks with regular edges resulting from phakomatoses. As with bone lesions, their distribution can be unilateral. Attention should be drawn, especially if the pigmentation mark is in the same embryological development area as the bone lesion. They are present in 50% of polyostotic FD cases. Endocrine affects are varied. (4). Precocious puberty is the most classic. This is more frequent in girls, but can easily be overlooked in boys. It is often identified by the start of menstrual bleeding and is associated with a significant advance in bone maturation. The association of precocious puberty with polyostotic FD and skin pigmentation marks is known as McCune-Albright syndrome (MAS), which has a significant predominance in females (5). Other endocrinopathies have been described, the most common within the scope of MAS being: hyperthyroidism (20 to 50 % of MAS cases) (6), acromegaly, with hyper-secretion of GH (10 % of MAS cases) (7), which is difficult to diagnose if the bone dysplasia affects the facial region, and more rarely hypercortisolism or primary hyperparathyroidism. The severity is highly variable from patient to patient and their management, well encoded in childhood, is less known in adulthood (4,8). The association of FD with intramuscular myxomas is known as Mazabraud’s syndrome (9). Myxomas, which are often multiple, neighbour bone lesions. The pathophysiology is unknown. If they are removed they often reappear, and their sarcomatous degeneration is rare (10). This is also the same for bone lesions. The frequency of sarcomas varies from 0.3 % for monostotic FD to 4 % for MAS with polyostotic FD. There are a wide number of different sarcomas: osteosarcoma, fibrosarcoma, chondrosarcoma or malignant fibrous hystiocytoma. The final association of interest to rheumatologists is hypophophatemic osteomalacia (11). FD, essentially in polyostotic forms, causes mesenchymatous lesions that secrete phosphaturic factor(s) such as FGF 23. A tubular phosphate leak should therefore be investigated in all patients with polyostotic FD, as it is present in approximately one case in two. However, phosphorous level measurements can be normal and the measurement of the clearance of phosphorous or the level of tubular reabsorption (maximum level of reabsorption reported by glomerular filtration rather than by the classic PRT) is preferable. This research is not without its practical Issues. Hypophosphatemia is linked to mineralisation problems in dysplasic bone tissue, but also non-dysplasic bone is affected. The discovery of a tubular phosphate leak requires specific therapeutic management to correct the phosphatemia (see the section on treatments).

REFERENCES

1 - Isler M, Turcotte R, Doyon J. Dysplasie fibreuse. Encycl Méd Chir (Editions Scientifiques et Médicales Elsevier SAS, Paris, tous droits réservés), Appareil locomoteur, 14-740, 2001, 8 p.

2 - Chapurlat RD, Delmas PD, Liens D, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res 1997;12:1746-52.

3 - Shenker A, Weinstein LS, Moran A, et coll. Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS. J Pediatr 1993 ; 123 : 509-18.

4 - Chanson Ph. Syndrome de McCune-Albright à l'âge adulte. In : N. Guérité, J. Leclère. Mises au point cliniques d'Endocrinologie, Nutrition et Métabolisme 2002. Franconville, Les 2ditions de Médecine Pratique, 2002. p. 23-36.

5 - Albright F, Butter AM, Hampton AO, Smith P. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females: report of five cases. N Engl J Med 1937;216:727-46.

6 - Mastorakos G, Mitsiades NS, Doufas AG, Koutras DA. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report. Thyroid 1987;7:433-9.

Chanson P, Dib A, Visot A, Derome PJ. McCune-Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases. Eur J Endocrinol 1994; 131 : 229-34.

7 - Lee PA, Van Dop C, Migeon CJ : McCune-Albright syndrome. Long-term follow-up. JAMA 1986;256:2980-4.

8 - Szendroi M, Rahoty P, Antal I, Kiss J. Fibrous dysplasia associated with intramuscular myxoma (Mazabraud's syndrome) : a long-term follow-up of three cases. J Cancer Res Clin Oncol 1998; 124 : 401-6.

9 - Ruggieri P, Sim FH, Bond JR, Unni KK. Malignancies in fibrous dysplasia. Cancer 1994 ;73 :1411-24.

10 - Orcel P, Burde MA, Kuntz D. Hypophosphatémies : le point. In : MF Kahn, D Kuntz, O Meyer, T Bardin, P Orcel, L'actualité rhumatologique 2004. Paris, Elsevier, 2004. p. 211-24.

 Created: 09 june 2010