Bone Marrow Injection to Replace Diseased Bone in Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome

Polyostotic fibrous dysplasia (PFD) is a sporadic disorder which affects multiple sites in the skeleton. The bone at these sites is rapidly resorbed and replaced by abnormal fibrous tissue. PFD may occur alone or as part of the McCune-Albright Syndrome (MAS), a syndrome originally defined by the triad of PFD, cafe au lait pigmentation of the skin, and precocious puberty. The bony lesions are frequently disfiguring and painful. In addition, depending on the location of the lesion, they can cause significant morbidity. Lesions in weight-bearing bones can lead to disabling fractures, while lesions in the skull can lead to compression of vital structures such as the cranial nerves.

Currently there are no clearly-defined systemic or local therapies for the bone disease, and results of the use of conventional surgical treatment of sites of impending fracture have been universally disappointing. In this study, we will treat osteolytic lesions in the long bones of the upper and lower extremities, the sites of potential fracture, with a novel surgical approach. This will involve 1) the removal of abnormal tissue through percutaneous aspiration, and 2) the use of skeletal precursor cells taken from the unaffected sites, mixed with a bone grafting substitute, and injected into the affected sites to bring about an improvement in local bone quality and overall patient function.

• INCLUSION CRITERIA:

Patients will be otherwise healthy women, men, and children, with polyostotic fibrous dysplasia (PFD)/McCune-Albright Syndrome (MAS).

Children will be greater than 4 years of age.

The diagnosis will be based on evidence of the clinical spectrum of the disease and confirmed by the presence of typical findings on bone biopsy.

All patients must be actively enrolled in the Screening and Natural History Protocol and possibly the Bisphosphonate Protocol.

Patients will be enrolled in the study if they have a lytic lesion of the humerus, femur, or tibia which satisfies at least one of the following criteria: the lesion encompasses at least 50% of the width of the bone at that point on both AP and lateral radiographs; the lesion has caused a change in the anatomical shape and contour of the bone; the lesion has a bone density less than 50% of the density of the contralateral, normal side.

Patients on previous or concomitant therapy are eligible for enrollment.

Patients on the Bisphosphonate Protocol must have received at least one month of treatment on that protocol before receiving a bone marrow injection in this protocol.

Women in childbearing age will be offered barrier methods of contraception to decrease the risk of pregnancy for a period of one year following the transplant. Subjects who become pregnant during year one of the study will be transferred to the inactive participant group. Pregnancy testing will be performed prior to research procedures and surgery. Subjects using oral contraceptive agents are included. Women without normal menstrual cycles will be offered hormone replacement therapy for a period of 3 cycles prior to treatment.

Subjects must agree to travel to NIH during the first 24 months and remain in the Bethesda area for the post-operative period as defined by protocol requirements.

Exclusion criteria

Subjects will be excluded if they receive phenobarbital or related antiepileptic agents, including Dilantin or Tegretol.

Medical problems which will preclude participation in the study include: pregnancy; chronic or active dermatological disease; chronic anemia (thalassemia, etc.); diabetes mellitus (fasting blood glucose in excess of 140 mg/dl); active or chronic pulmonary disease including COPD, chronic bronchitis, or asthma requiring medications; active or chronic gastrointestinal disease including gastric and duodenal ulcer disease and inflammatory bowel disease; history of cancer except for dermal lesions; intestinal malabsorption, chronic or active renal disease including a serum creatinine above 1.8 mg/dl; chronic or active hepatic disease including hepatitis; HIV infection.

Subjects may not smoke more than one pack of cigarettes per day.

Alcohol consumption must be less than 1.5 oz per day, without binge drinking.

Subjects should have no dietary aberrations and no history of anorexia nervosa within the past 10 years.

Subjects must be willing to receive transfusions of blood products if it is deemed medically necessary to preserve their well-being or their life.

Patients will be excluded if they have a history of an allergy to all of the following antibiotics: penicillin, tetracycline, and cephalosporins.