Presentation Clinical Presentation Aetiology Imaging Treatments MCCUNE-ALBRIGHT SYNDROME
Congress Events Profidys Clinical Trial
Association des Malades Porteurs du Syndrome McCune-Albright ORPHANET : maladie rares & médicaments orphelins Fondation Fibrous Dysplasia European Science Fondation
Dysplasie fibreuse des os contact



Therapeutic management of fibrous dysplasia of bone (FD) is based on the clinical symptoms (pain, deformities, fractures, neurological complications) and the pathophysiological mechanisms of the disease. FD is caused by a somatic mutation of the subunit of the G protein, as a result of an over expression of c-fos, consequently resulting in an osteoblast differentiation defect. These undifferentiated stromal cells synthesise a bone matrix that is disorganised, abnormally mineralised and an excess of IL-6 leads to a hyper-production of osteoclasts associated with hyper-resorption of the bone.
In certain patients, especially those with polyostotic forms, phosphate diabetes can also be observed, which is sometimes the source of these mineralisation issues seen. The association of endocrine problems (essentially precocious puberty as a result of this disease) and café-au-lait skin pigmentation marks with fibrous dysplasia is known as McCune-Albright syndrome. The varied biological and clinical appearance of the disease allows different therapy routes to be defined.




The existence of a hyper-resorption of the bone, notably present on histological sections of large active osteoblasts, led to an analogy with Paget’s disease – a disease of the osteoclasts – being made, and consequently this led to anti-resorbtion agents like bisphosphonates being used, even though FD is a disease of the osteoblasts. The first patients were treated at the end of the 1980s, with the then most effective treatment for Paget’s disease, intravenous pamidronate [1], at a dose of 180 mg perfused every 6 months.

1.1 Clinical trial results

The efficacy of bisphosphonates was assessed in a small number of series with approximately 10 patients in each. Due to the rarity of the disease, the trials were not placebo controlled. The products tested were mainly pamidronate (Aredia®, and generic products) [2-7], and some observations of patients who received alendronate were also published [4, 8]. In a French series lasting an average of 4 years (with a maximum of 12 years) [2, 3], a significant reduction in the intensity of pain and the number of painful sites could be noted. On average, the intensity of the pain was reduced by two thirds. Six moths after the first perfusion, half of the patients saw a decrease or a disappearance of pain. An additive effect from subsequent perfusions could also be seen. Fourteen percent of patients did not see a significant reduction in the intensity of the bone pain. The reappearance of pain is possible, but generally alleviated with a further dose of pamidronate. Similar effects were observed in other patient series [4, 5, 8]. Bone turnover is also reduced by the treatment, in patients with a high rate of bone resorption before starting on the bisphosphonate treatment. The response to treatment with pamidronate is quick and the effect of the doses is additive with a standardisation of bone turnover markers that can take up to 2 years. The markers which appear to be the most useful for therapeutic monitoring are total alkaline phosphatase, osteocalcin and CTX.

A positive effect on x-rays could also be observed in approximately half of the patients treated, with a partial or complete filling of the osteolytic areas and/or a thickening of the cortex. This phenomenon was noted in many series, except that of Plotkin et al [6]. The different therapeutic regime, without a systematic supplement of vitamin D in patients with phosphate diabetes is possibly responsible for this difference in radiological response. Patients presenting with a genuine radiological result were not observed for a relatively long time, greater than or equal to 18 months. A healthy increase in bone mineral density, in the order of 15 % in the hip area, has been recorded with pamidronate and alendronate [3, 7, 8], which is also hoped to have an anti-fracturing effect.

1.2 In practice

The therapeutic regime used in general for adult patients comprises of the administration of intravenous pamidronate at a dose of 60 mg per day over three days, under slow perfusion over 4 hours in 500 ml of 9 ‰ NaCl. In children, the dose is 3 days of 1 mg/kg/day. This dose is repeated every 6 months for at least 2 to 3 years, then for patients who have a form that has responded particularly well to treatment, or is moderately severe, the doses can be spaced at yearly intervals, or even stopped completely, with biological and radiological clinical monitoring. The treatment is well tolerated, with the possibility of one third of patients having a flu-like temperature, often accompanied by myalgia and bone pain. This reaction only lasts for 24 to 48 hours and responds well to paracetamol and does not return in future doses. Treatment with bisphosphonates requires women of child bearing age to use contraception. A calcium supplement (1 g/day) and vitamin D3 (800 IU/day) is recommended in association with bisphosphonates as these patients, who are often young when being treated, frequently present with a vitamin D deficiency (25% in the last published series [3]). In addition, the dysplasic bone tissue is particularly sensitive to secondary hyperparathyroidism, which is likely to aggravate the lesions [9]. This supplement should also be able to play a preventative role in the frequent mineralisation problems found in FD.



1.3 Identifying the presence of phosphate diabetes

Approximately half of patients who suffer with polyostotic forms of FD present with renal phosphorus wasting [10], which leads to a risk of mineralisation problems in healthy as well as dysplasic bone tissue [2]. Measurement of phosphorus levels is not a good diagnostic test in patients as they are inconsistent, and measurement of the maximum phosphorus reabsorption level is preferred, carried out by glomerular filtration (TmPi/GFR). This measurement should be systematic in the diagnosis of FD, so that the future management can be properly planned.

1.4 Phosphorus supplements in practice

Two products are commercially available in France in an oral form, Phosphoneuros® and Phosphore Alko®. Phosphoneuros® is a drinkable solution, which contains 78.8 mg of phosphorus per 10 drops. The usual dose is 150 to 200 drops per day divided up and taken at 3 to 5 different times (or 1.2 to 1.6 g/day). Digestive tolerance is often poor, with nausea, stomach pain and diarrhea. Splitting the dose and taking it at the end of a meal can improve these symptoms. Phosphore Alko ® is easier to use, with two tablets of 750 mg to be taken per day. This phosphorus supplement is systematically prescribed in association with calcitriol (Rocaltrol®), at a dose of 0.25 to 1 mg/day. Phosphorus alone is not capable of normalising phosphorous levels [11]. However, the use of calcitriol must be accompanied by strict monitoring due to the risk of hypercalciuria and, thus, urolithiasis. It is therefore recommended that calciuria levels are measured over a 24 hour period, and possibly carry out renal ultrasounds.



1.5 Different techniques

Surgery had long been the only therapeutic option for FD. Procedures consist, in the case of a fracture, of carrying out osteosynthesis with a possible bone graft. This graft must be done using a cortical graft (taken from the fibula) and not a spongy bone graft from the iliac crest, as these are always resorbed. Preventative procedures are also performed, with the spot removal of lesions and a bone grafts (cortical). Preventative osteosynthesis is carried out at the same time. Bone deformities are sometimes subject to correction by osteotomy, which is generally accompanied by another procedure (osteosynthesis etc.).

1.6 Indications

Preventative surgery is indicated when the risk of fracture is high, for example, in the presence of a large osteolytic lesion, a thinning of the bone or a cortical crack, especially in a weight bearing bone like the femur, where a fracture would have serious consequences. Children and adolescents are the focus of particular attention as the majority of fractures occur during this time. Osteosynthesis equipment is specifically modified for growing bone, with the use, for example, of telescopic nails.




The specificity of precocious puberty relating to McCune-Albright syndrome lies in its peripheral character, with hormonal secretion from the ovaries (or, more rarely, from the testicles), rather than the early onset of puberty due to the early release of gonadotropins, as in the majority of other precocious puberty aetiologies. Treatment will therefore need different drugs, which directly inhibits the synthesis of gonadal sex steroids, rather than the LH-RH analogues taken in cases of precocious puberty with a central origin. Therefore the drugs used will be cyproterone acetate or testolactone.




DF located in the vertebrae or the cranium can lead to neurological complications. Medullary compression, uniquely due to vertebral FD will be the subject of emergency decompression surgery. Compression of the cranial nerves are also possible, the most frequent being that of the optic nerve from FD from an obstruction of the optic canal, in cases of DF of the ethmoid or sphenoid bones. Even in cases of obstruction of the optical canal with compression of the optic nerve, the visual prognosis is not that bad long term (stability in 90% of patients) [12]. The identification of such lesions may not necessarily lead to decompression surgery, which may cause bleeding with a certain risk to vision. Decompression procedures are therefore carried out on patients who have had a change in their vision. Specifically, checks with a scanner must be made to verify the condition of the optic canals of patients suffering with cranio-facial FD. If a uni- or bilateral obstruction is found, perennial monitoring of the field of vision is required, with decompression surgery discussed if a net reduction is seen during an ophthalmological examination.




Treatment with bisphosphonates has been shown to reduce the intensity of pain, and improve the radiological appearance, but their indication is not yet fully detailed. It is likely to be used to treat patients of forms with osteolytic areas, with the risk of fracture and those that are in pain. However, the level of analgesia remains uncertain, as these products have been assessed in open studies. The therapy clinical trials now running (alendronate with placebo control in the United States and the PROFIDYS clinical trial in Europe) should allow therapeutic indication and the value of the analgesic effect to be determined. Calcium and vitamin D or phosphorus and calciterol supplements can be useful in optimising bisphosphonate treatments and avoiding bone mineralisation problems.




1 - Liens D, Delmas PD, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet 1994; 343: 953-4.
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 - Chapurlat RD, Hugueny P, Delmas PD, Meunier PJ. Treatment of fibrous dysplasia of bone with intravenous pamidronate: predictors of response to treatment and long-term effectiveness. Bone 2004; 35: 235-42.
4- Lane JM, Khan SF, O'Connor WJ, et coll. Bisphosphonate therapy in fibrous dysplasia. Clin Orthop Rel Res 2001; 382: 6-12.

5 - Isaia GC, Lala R, Defilippi C, et coll. Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia. Calcif Tissue Int 2002; 71: 121-28.

6 - Plotkin H, Rauch F, Zeitlin L, et coll. Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone. J Clin Endocrinol Metab 2003; 88: 4569-75.

7 - Parisi MS, Oliveri B, Mautalen CA. Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia. Bone 2003; 33: 582-8.

8 - Weinstein RS. Long-term aminobisphosphonate treatment of fibrous dysplasia: spectacular increase in bone density. J Bone Miner Res 1997; 12: 1314-15.
9 - Corsi A, Collins MT, Riminucci M, et coll.
Osteomalacic and hyperparathyroid changes in fibrous dysplasia of bone: core biopsy studies and clinical correlations. J Bone Miner Res 2003; 18: 1235-46.
10 - Collins MT, Chebli C, Jones J, et coll.
Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia. J Bone Miner Res 2001; 16: 806-13.
11 - Glorieux FH, Scriver CR, Reade TM, et coll.
Use of phosphate and vitamin D to prevent dwarfism and rickets in X-linked hypophosphatemia. N Engl J Med. 1972; 287: 481-7.

12 - Lee JS, Fitzgibbon E, Butman JA, et al. Normal vision despite narrowing of the optic canal in fibrous dysplasia. N Engl J Med 2002; 347: 1670-6.




Created: 09 june 2010