Study of Denosumab for Prevention of Skeletal Disease Progression in Children With Fibrous Dysplasia

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Confirmed diagnosis of fibrous dysplasia

• Age 4 to 14 years

• Concurrent enrollment in the companion Screening and Natural History protocol 98-D-0145

• Provision of signed and dated informed consent form

• Stated willingness of guardian/Legally Authorized Representative (LAR) to complywith all study procedures and availability for the duration of the study

• Ability of guardian/LAR to understand and the willingness to sign a written informedconsent document

• For females of reproductive potential: agreement to use highly effectivecontraception for during study participation. Highly effective contraception methodsinclude:

• Total abstinence. Periodic abstinence (e.g., calendar, ovulation,symptothermal, post-ovulation methods) and withdrawal are not acceptablemethods of contraception.

• Combination of the following (a+b or a+c, or b+c):

• Use of oral, injected or implanted hormonal methods of contraception orother forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermalhormone contraception

• Placement of an intrauterine device (IUD) or intrauterine system (IUS)

• Barrier methods of contraception: Condom or Occlusive cap (diaphragm orcervical/vault caps) with spermicidal foam/gel/film/cream/vaginalsuppository

• For males of reproductive potential: use of condoms or other methods to ensureeffective contraception with partner

• Minimum body weight of 12 kilograms

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Pregnancy or lactation

• Known allergic reactions to denosumab

• Prior history, or current evidence, of osteomyelitis/osteonecrosis of the jaw

• Planned invasive dental procedure for the course of the study

• Presence of non-healed dental or oral surgery

• Orthopedic procedure performed less than 6-weeks prior to first day of the denosumabadministration (Day 0)

• Acute fracture less than 6-weeks prior to first day of the denosumab administration (Day 0)

• Serum calcium or albumin-adjusted serum calcium below the normal range for the NIHlaboratory (patients will be eligible for re-screening after a repletion periodlasting up to 6 months)

• 25-hydroxyvitamin D level than 20 ng/mL (patients will be eligible for re screeningafter a repletion period lasting up to 6 months)

• Untreated or inadequately treated hypophosphatemia as determined by the principalinvestigator (patients will be eligible for re-screening after initiation oroptimization of phosphorus replacement no longer than 6 months)

• Inability to comply with a non-sedated 18F-NaF PET/CT (subjects will be eligible forre- screening after 6 months)

• Use of another investigational agent within the last 3 months prior to the first dayof the denosumab administration (Day 0)

• Have any condition which in the opinion of the PI could present a concern forsubject safety or difficulty with data interpretation.