Role of the Protein Osteoprotegerin in the Bone Health of Women With Congenital Adrenal Hyperplasia - Full Text View

Purpose

21-hydroxylase deficiency (21-OHD) is an inherited disorder that results from a mutation on the CYP21A2 gene. It affects the adrenal glands and is the most common cause of congenital adrenal hyperplasia (CAH). 21-OHD CAH causes the body to produce an insufficient amount of cortisol and an excess of androgen, the type of hormone that produces male characteristics. The primary treatment for 21-OHD CAH, glucocorticoid replacement therapy, has been shown to cause bone loss. However, the elevated hormone levels caused by 21-OHD CAH may increase production of the protein osteoprotegerin (OPG), which in turn may protect against bone loss. This study will compare bone density and OPG levels in women who have 21-OHD CAH and have undergone a lifetime of glucocorticoid replacement therapy to that in women who have neither of these criteria. In doing so, the study will aim to determine the relationship between OPG and bone loss.

Condition
Adrenal Hyperplasia, Congenital

Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Cross-Sectional
Official Title:	Potential Modulatory Role of Osteoprotegerin in Bone Metabolism of Patients With 21-Hydroxylase Deficiency

Resource links provided by NLM:

Genetics Home Reference related topics: 21-hydroxylase deficiency 3-beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency Cushing disease persistent Müllerian duct syndrome

MedlinePlus related topics: Bone Density

U.S. FDA Resources

Further study details as provided by Office of Rare Diseases (ORD):

Primary Outcome Measures:

Comparison of levels of OPG [ Time Frame: Measured throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Comparison of bone mineral density [ Time Frame: Measured throughout the study ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

With participant's permission, 5 mL of blood will be stored for potential new blood markers in the future.

Estimated Enrollment:	40
Study Start Date:	April 2008
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts
1 Women in this group will have 21-OHD CAH.
2 Women in this group will be healthy controls and will not have 21-OHD CAH.

Detailed Description:

Because of the excess of androgen caused by 21-OHD CAH, women with CAH may exhibit some male-like characteristics. Glucocorticoids are a member of a class of drugs called corticosteroids, which are used in hormone replacement therapy. In order to counteract the effects of 21-OHD CAH, women with the disease are given hormone replacement therapy with glucocorticoids beginning at infancy. Glucocorticoids are known to cause bone loss. Despite many years of treatment with glucocorticoids, however, young women with 21-OHD CAH seem to be protected against bone loss. Researchers believe that the increased androgen levels in these women leads to increased estrogen levels, which in turn increases OPG production. The increase in OPG levels may protect women against bone loss. This study will evaluate bone density and OPG levels in women with and without 21-OHD CAH to determine the relationship between OPG and bone loss.

Participants in this observational study will attend only one study visit. At this visit, they will undergo a blood draw; a scan of their lower spine, hip, and forearm; height and weight measurements; and a body fat analysis test. This last test will entail a weak and painless electrical signal being sent from foot to foot. Participants will not attend any follow-up visits for this study.

Eligibility

Ages Eligible for Study:	20 Years to 35 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

Premenopausal women between the ages of 20 and 35 who have 21-OHD CAH or do not have 21-OHD CAH.

Criteria

Inclusion Criteria:

For People with 21-OHD CAH:

21-OHD CAH has been documented by molecular genetic analysis (mutations on CYP21A2 gene on both parental alleles)
Treatment with glucocorticoid replacement since infancy (begun within the first year)
Available hormonal data and treatment details over the 5 years prior to study entry
Premenopausal

For Healthy Controls:

No diagnosis of 21-OHD CAH, as confirmed by molecular genetic analysis
No first degree relative is enrolled as a 21-OHD CAHparticipant
Premenopausal

Exclusion Criteria:

Medical disorder or treatment with medications known to affect bone density (other than glucocorticoids for 21-OHD CAH patients), including, but not limited to growth hormone, IGF-I, depo-medroxyprogesterone acetate, biphosphonates, oral contraceptives, androgens, thyroxine, or aromatase inhibitors
Pregnant
Any smoking within the 6 months prior to study entry
Cardiac pacemaker or other implanted electronic medical device

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694525

Contacts

Contact: Karen Lin Su, MD

212-241-7847

karen.su@mssm.edu

Locations

United States, New York
Mount Sinai School of Medicine	Recruiting
New York, New York, United States, 10029
Principal Investigator: Karen Lin Su, MD
Sub-Investigator: Maria I. New, MD
Sub-Investigator: Saroj Nimkarn, MD
Sub-Investigator: Mone Zaidi, MD, PhD
Sub-Investigator: Henry Bone, MD

Sponsors and Collaborators

Office of Rare Diseases (ORD)

Investigators

Study Chair:

Karen Lin Su, MD

Mount Sinai School of Medicine

More Information

Publications:

Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone. 2004 Apr;34(4):593-8. Review. No abstract available.

Paganini C, Radetti G, Livieri C, Braga V, Migliavacca D, Adami S. Height, bone mineral density and bone markers in congenital adrenal hyperplasia. Horm Res. 2000;54(4):164-8.

King JA, Wisniewski AB, Bankowski BJ, Carson KA, Zacur HA, Migeon CJ. Long-term corticosteroid replacement and bone mineral density in adult women with classical congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2006 Mar;91(3):865-9. Epub 2005 Nov 8.

Kudlacek S, Schneider B, Woloszczuk W, Pietschmann P, Willvonseder R; Austrian Study Group on Normative Values of Bone Metabolism. Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone. 2003 Jun;32(6):681-6.

Hagenfeldt K, Martin Ritzén E, Ringertz H, Helleday J, Carlström K. Bone mass and body composition of adult women with congenital virilizing 21-hydroxylase deficiency after glucocorticoid treatment since infancy. Eur J Endocrinol. 2000 Nov;143(5):667-71.

Responsible Party:	Maria I. New, MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:	NCT00694525 History of Changes
Other Study ID Numbers:	RDCRN 5611
Study First Received:	June 6, 2008
Last Updated:	June 1, 2009
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

21OHD
21-hydroxylase deficiency
CAH

Additional relevant MeSH terms:

Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenocortical Hyperfunction
Hyperplasia
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn

Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Gonadal Disorders
Pathologic Processes

ClinicalTrials.gov processed this record on May 22, 2013