Evaluation and Treatment of Skeletal Diseases

Human diseases are commonly manifested in the skeletal system. The skeleton may be the
primary or secondary target of the disease and the disease may be congenital or acquired.
While understanding of the molecular and cellular biology of bone and mineral disorders has
increased in the last several years, much remains to be understood about the underlying
biology of the skeleton. The gaps in the understanding of skeletal biology are evident in the
paucity of tissue-specific therapies for skeletal diseases.

Within this study, we plan to obtain tissue and clinical specimens from outside institutions
as well as to evaluate subjects with bone and mineral disorders at the NIH Clinical Center.
Subjects will undergo clinically indicated testing and possibly receive treatment, which will
be limited to therapies based on the best professional judgment of the investigators and
treatment with medications commercially available under FDA law.

Objectives:

The objectives of this protocol are to:

1. allow for the receipt of tissues and clinical specimens from investigators outside and
inside the NIH

2. provide a protocol within which subjects with common and rare disorders of bone and
mineral metabolism can be studied, evaluated and treated at NIH

3. provide a protocol under which trainees can evaluate subjects with bone and mineral
disorders

4. provide a pool of subjects with bone and mineral disorders, from which research
questions will arise and from which future research studies will be generated.

Study Population:

The study population will include subjects:

- with a known or suspected bone disease and/or with a known or suspected disorder of
mineral metabolism

- Subjects who meet eligibility criteria will be accepted regardless of gender, race, or
ethnicity.

Design:

This protocol is a training, evaluation and treatment protocol.

Outcome measures:

1. To successfully enroll, evaluate, and manage subjects with common and rare bone and
mineral metabolism disorders. The purposes for doing this are: a) educating trainees and
investigators and b) providing a mechanism by which subjects with diseases of uncertain
or unknown diagnoses can be evaluated.

2. To collect or receive research and clinical specimens of common and rare bone and
mineral metabolism disorders from subjects seen at outside medical facilities as well as
those seen at the NIH. Specimens will be collected for research purposes.

3. Analysis of research and subject outcome data collected from the subjects enrolled in
this study will generate future research studies related to common and rare bone and
mineral metabolism disorders.

- INCLUSION CRITERIA:

1. Age 2 months or older

2. Subjects with known or suspected bone disease, as demonstrated by any one of the
following: a fracture, or abnormal bone findings on x-ray, CT scan, MRI, or bone
densitometry, and/or a medical history consistent with or suggestive of a bone
disease.

3. Subjects with a known or suspected disorder of mineral metabolism, as
demonstrated by any one of the following: laboratory measurement above or below
the reference values for either blood or urine calcium, phosphorus, magnesium,
parathyroid hormone or vitamin D, or other measures of mineral metabolism, and/or
a medical history consistent with or suggestive of a disorder of mineral
metabolism.

EXCLUSION CRITERIA:

1. Subjects unwilling or unable to abide by procedures of protocol.