Clinical trial NCT00694525: Role of the Protein Osteoprotegerin in the Bone Health of Women With Congenital Adrenal Hyperplasia
Official title: Potential Modulatory Role of Osteoprotegerin in Bone Metabolism of Patients With 21-Hydroxylase Deficiency
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Adrenal Hyperplasia, Congenital
Keywords: 21OHD
21-hydroxylase deficiency
CAH
Lead sponsor: Office of Rare Diseases (ORD)
Sponsor class: NIH
First posted: 2008-06-10
Enrollment: 40
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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.

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 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

Primary outcomes:
measure: Comparison of levels of OPG
timeFrame: Measured throughout the study
Secondary outcomes:
measure: Comparison of bone mineral density
timeFrame: Measured throughout the study
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Karen Lin Su, MD
role: STUDY_CHAIR
References:
citation: Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone. 2004 Apr;34(4):593-8. doi: 10.1016/j.bone.2003.11.026. No abstract available.
citation: 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. doi: 10.1159/000053253.
citation: 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. doi: 10.1210/jc.2005-0745. Epub 2005 Nov 8.
citation: 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. doi: 10.1016/s8756-3282(03)00090-5.
citation: Hagenfeldt K, Martin Ritzen E, Ringertz H, Helleday J, Carlstrom 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. doi: 10.1530/eje.0.1430667.