MACS and Healthy Volunteers Bone Study

Effects of Abnormal Steroid Metabolome on Bone Strength and Quality, Bone Density, Bone Remodeling, and Body Composition in Patients With MACS and Healthy Volunteers.

Adrenal adenoma is detected in 5-7% of adults and demonstrates mild autonomous cortisol secretion (MACS, dexamethasone suppression test >1.8 mcg/dl) in 50% of individuals with adenoma. Published reports suggest a 48%-52% 2-year incidence of new vertebral fractures in patients with MACS without any significant changes in bone density measurements. A disproportionate decrease in bone quality versus density or other factors such as sarcopenia potentially contribute to development of new vertebral fractures. Determining which specific abnormalities in the steroid metabolome affect bone density, quality and strength as well as bone remodeling markers and body composition will potentially serve as a diagnostic biomarker of clinical significance.

Study Overview

• Status: Completed
• Conditions: MACS Syndrome

Detailed Description

In this study, we will determine whether patients with MACS (versus healthy age and sex matched controls) demonstrate: 1) decreased bone strength and quality disproportionate to the decrease of bone density and 2) abnormalities in the steroid metabolome correlate with the degree of abnormalities in bone parameters. In a cross-sectional study of 75 patients with MACS and 75 age- and sex-matched healthy controls, we will determine the relationship of the steroid metabolome to measurements of bone density, quality and strength, bone turnover markers, as well as body composition. All patients will be interviewed in regards to their health, to include questions on bone health, frailty, cognition (NIH toolbox), and quality of life. We will measure 1) BMD (bone mineral density) at the lumbar spine, hip and radius and body composition using dual-energy X ray absorptiometry (DXA), 2) radial and tibial bone microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT), 4) bone turnover markers (osteocalcin, PINP, CTx, sclerostin). 5) Age reader measurement, 6) hand grip measurement, 7) 6 minute walk test. All patients will provide a 24 h urine for steroid metabolome analysis. For primary outcomes, we will determine if steroid metabolome profiling better predicts abnormal bone strength (as measured by trabecular bone volume/tissue volume [BV/TV] ratio).

• Study Type: Observational
• Enrollment (Actual): 380

Contacts and Locations

• Study Contact: Name: Vanessa Fell; Phone Number: 507-266-6068; Email: fell.vanessa@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

MACS participants either male or female who are at least 18 years of age who fulfill the inclusion criteria.

Description

Inclusion Criteria:

• Patients with MACS
• Age 18-no maximum
• exogenous steroids therapy within the last 5 years ( for more than 3 months , prednisone equivalent >7.5 mg daily)
• steroid hormone replacement therapy
• any drug therapy affecting bone metabolism
• recent fracture

Exclusion Criteria:

• exogenous steroids therapy within the last 5 years ( for more than 3 months , prednisone equivalent >7.5 mg daily)
• steroid hormone replacement therapy ( for adrenal insufficiency, hypogonadism, menopause)
• therapy for osteoporosis
• any drug therapy affecting bone metabolism
• comorbidities affecting steroid metabolome or bone metabolism
• recent fracture

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
patients with MACS; Patients with adrenal adenoma and dexamethasone suppression test >1.8 mcg/dl
healthy controls; no history of adrenal and pituitary disease, no exogenous steroids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BV/TV ratio	measured by computed tomography	0-24 months
steroid metabolome	24h urine steroid profiling	0-24 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Irina Bancos, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2019
• Primary Completion (Actual): December 11, 2023
• Study Completion (Actual): December 11, 2023

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 18-009787

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No