CT-Based Changes in Bone and Marrow Among Patients on Oral Steroids

The goal of this study is to assess the feasibility of emerging CT-based tools to measure changes in central and peripheral bone density, micro-structure, and marrow adipose tissue (MAT) among patients treated with oral steroids.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Bone Density, Low; Oral Steroid-Dependent Asthma (Disorder)
• Intervention / Treatment: Radiation: CT Scan; Radiation: DXA Scan; Other: Steroid Intake Questionnaire

Detailed Description

This study aims to prove that emerging CT-based tools are suitable to measure changes in central and peripheral bone density, geometry, micro-structure, and marrow adipose tissue (MAT) among patients treated with oral steroids. To do this, investigators will recruit 10 non-smokers (defined as < 10 pack-year smoking history) age 25-45 years with a diagnosis of severe, persistent asthma who either chronically use oral steroids or do not use any oral steroids. Participants will undergo dual-energy X-ray absorptiometry (DXA), dual-energy mid-tibia CT, high-resolution single-energy ankle CT, and low-radiation hip CT scans at baseline and 6-month follow-up visits. The images obtained will be used to analyze cross-sectional differences in central and peripheral bone density, geometry, micro-structure, and MAT between patients using oral steroids versus those who do not use any oral steroids. Differences in imaging at baseline and six-month follow visits will be used to analyze longitudinal bone changes among patients with oral steroid treatment.

• Study Type: Observational
• Enrollment (Estimated): 12

Contacts and Locations

• Study Contact: Name: Taylor M Haynes, MS; Phone Number: 319-356-1785; Email: taylor-haynes@uiowa.edu
• Study Contact Backup: Name: Punam K Saha, PhD; Phone Number: 319-335-5959; Email: punam-saha@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Taylor M Haynes, MS; Phone Number: 319-356-1785; Email: taylor-haynes@uiowa.edu
      • Contact: Kimberly Sprenger, RN; Phone Number: 319-353-8862; Email: kimberly-sprenger@uiowa.edu
      • Principal Investigator: Punam K Saha, PhD
      • Principal Investigator: Alejandro Comellas, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

We plan to enroll 12 subjects, divided into two groups of 6. We will recruit 6 subjects with a diagnosis of severe, persistent asthma who have been taking oral GCs for 1.5-11 months. We will also recruit 6 subjects with a diagnosis of severe, persistent asthma who have not used any oral GCs in the last 12 months.

Description

Inclusion Criteria:

• Inclusion (all subjects):

  • Diagnosis of severe, persistent asthma (defined as using both a long-acting beta-agonist AND a high-dose inhaled steroid)
  • Age 25-45

• Inclusion (oral steroid group):

  • Chronic treatment with oral steroids for at least 45 days but less than 1 year

Exclusion Criteria:

• Exclusion (all subjects):

  • Pregnant or breastfeeding
  • History of any cancer, excluding non-melanoma skin cancer
  • Currently receiving dialysis
  • History of any lower extremity fracture
  • Hip or knee replacement
  • Non-ambulatory
  • Greater than 10 pack-year smoking history
  • BMI > 50
  • Age < 25 or > 45
  • Current or past use of FDA-approved medication for osteoporosis:

Bisphosphonates (Alendronate/Fosamax, Ibandronate/Boniva, Risedronate/Actonel/Atelvia, Zoledronic Acid/Reclast) Calcitonin (Fortical, Miacalcin) Selective Estrogen Receptor Modulator (Raloxifene/Evista) Parathyroid Hormone Analogue (Teriparatide/Forteo) Monoclonal Antibody (Denosumab/Prolia)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Marrow Adipose Tissue	Marrow adipose tissue fraction at 14-16% location of the distal tibia from DECT ankle scans will be computed and compared between oral steroid and control groups.	Baseline
Cortical Bone Density	Cortical bone density will be computed through CT scanning at 4-6% and 12-14% distal tibia locations and compared between oral steroid and control groups.	Baseline
Peripheral Bone Density	Peripheral bone density will be computed through CT scanning at 4-6% and 12-14% distal tibia locations and compared between oral steroid and control groups.	Baseline
Bone Geometry and Microstructure	Hip MDCT scans will be used compute volumetric bone mineral density (vBMD) measures over trabecular and cortical bone compartments at femoral head, femoral neck, greater trochanter, and lesser trochanter. These measurements will be compared between oral steroid and control groups.	Baseline
DXA Body Composition Analysis (fat mass, lean mass, percent fat)	DXA scans will be used to acquire bone and soft tissue measures that will allow for the calculation of body composition measures, which will then be compared between oral steroid and control groups.	Baseline
DXA Bone Mineral Density	DXA Bone Mineral Density score will be obtained using standard DXA scans and compared between oral steroid and control groups.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Marrow Adipose Tissue	Marrow adipose tissue fraction at 14-16% location of the distal tibia from DECT ankle scans will be computed and evaluated over time in the oral steroid group.	Change from baseline to 6-month follow up visit
Cortical Bone Density	Cortical bone density will be computed through CT scanning at 4-6% and 12-14% distal tibia locations and evaluated over time in the oral steroid group.	Change from baseline to 6-month follow up visit
Peripheral Bone Density	Peripheral bone density will be computed through CT scanning at 4-6% and 12-14% distal tibia locations and evaluated over time in the oral steroid group.	Change from baseline to 6-month follow up visit
Bone Geometry and Microstructure	Hip MDCT scans will be used compute volumetric bone mineral density (vBMD) measures over trabecular and cortical bone compartments at femoral head, femoral neck, greater trochanter, and lesser trochanter. Changes in these measurements from baseline to 6-month follow up visits will be computed for the oral steroid group.	Change from baseline to 6-month follow up visit
DXA Body Composition Analysis (fat mass, lean mass, percent fat)	DXA scans will be used to acquire bone and soft tissue measures that will allow for the calculation of body composition measures. Change over time from baseline to 6-month follow up visit will be computed for the oral steroid group.	Change from baseline to 6-month follow up visit
DXA Bone Mineral Density	DXA Bone Mineral Density score will be obtained using standard DXA scans. These scores will be compared at baseline and 6-month follow up visits for the oral steroid group.	Change from baseline to 6-month follow-up visit

Collaborators and Investigators

• Sponsor: University of Iowa
• Investigators: Principal Investigator: Punam K Saha, PhD, University of Iowa

Publications and helpful links

General Publications

• Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res. 2000 Jun;15(6):993-1000. doi: 10.1359/jbmr.2000.15.6.993.
• Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007 Oct;18(10):1319-28. doi: 10.1007/s00198-007-0394-0. Epub 2007 Jun 14.
• Clowes JA, Peel N, Eastell R. Glucocorticoid-induced osteoporosis. Curr Opin Rheumatol. 2001 Jul;13(4):326-32. doi: 10.1097/00002281-200107000-00015.
• Wehrli FW, Saha PK, Gomberg BR, Song HK, Snyder PJ, Benito M, Wright A, Weening R. Role of magnetic resonance for assessing structure and function of trabecular bone. Top Magn Reson Imaging. 2002 Oct;13(5):335-55. doi: 10.1097/00002142-200210000-00005.
• Barger-Lux MJ, Recker RR. Bone microstructure in osteoporosis: transilial biopsy and histomorphometry. Top Magn Reson Imaging. 2002 Oct;13(5):297-305. doi: 10.1097/00002142-200210000-00002.
• Bell KL, Loveridge N, Power J, Garrahan N, Meggitt BF, Reeve J. Regional differences in cortical porosity in the fractured femoral neck. Bone. 1999 Jan;24(1):57-64. doi: 10.1016/s8756-3282(98)00143-4.
• Kleerekoper M, Villanueva AR, Stanciu J, Rao DS, Parfitt AM. The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tissue Int. 1985 Dec;37(6):594-7. doi: 10.1007/BF02554913.
• Legrand E, Chappard D, Pascaretti C, Duquenne M, Krebs S, Rohmer V, Basle MF, Audran M. Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis. J Bone Miner Res. 2000 Jan;15(1):13-9. doi: 10.1359/jbmr.2000.15.1.13.
• Legrand E, Audran M, Guggenbuhl P, Levasseur R, Chales G, Basle MF, Chappard D. Trabecular bone microarchitecture is related to the number of risk factors and etiology in osteoporotic men. Microsc Res Tech. 2007 Nov;70(11):952-9. doi: 10.1002/jemt.20501.
• Moore RJ, Durbridge TC, McNeil PJ, Parkinson IH, Need AG, Vernon-Roberts B. Trabecular spacing in post-menopausal Australian women with and without vertebral fractures. Aust N Z J Med. 1992 Jun;22(3):269-73. doi: 10.1111/j.1445-5994.1992.tb02124.x.
• Mosekilde L. Consequences of the remodelling process for vertebral trabecular bone structure: a scanning electron microscopy study (uncoupling of unloaded structures). Bone Miner. 1990 Jul;10(1):13-35. doi: 10.1016/0169-6009(90)90046-i.
• Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. 1983 Oct;72(4):1396-409. doi: 10.1172/JCI111096.
• Parfitt AM. Implications of architecture for the pathogenesis and prevention of vertebral fracture. Bone. 1992;13 Suppl 2:S41-7. doi: 10.1016/8756-3282(92)90196-4.
• Recker RR. Architecture and vertebral fracture. Calcif Tissue Int. 1993;53 Suppl 1:S139-42. doi: 10.1007/BF01673423.
• Vesterby A, Gundersen HJ, Melsen F, Mosekilde L. Marrow space star volume in the iliac crest decreases in osteoporotic patients after continuous treatment with fluoride, calcium, and vitamin D2 for five years. Bone. 1991;12(1):33-7. doi: 10.1016/8756-3282(91)90052-k.
• Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, Nevitt MC, Cummings SR; Osteoporotic Fractures Research Group. BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res. 2003 Nov;18(11):1947-54. doi: 10.1359/jbmr.2003.18.11.1947.
• Li C, Jin D, Chen C, Letuchy EM, Janz KF, Burns TL, Torner JC, Levy SM, Saha PK. Automated cortical bone segmentation for multirow-detector CT imaging with validation and application to human studies. Med Phys. 2015 Aug;42(8):4553-65. doi: 10.1118/1.4923753.
• Saha PK, Liu Y, Chen C, Jin D, Letuchy EM, Xu Z, Amelon RE, Burns TL, Torner JC, Levy SM, Calarge CA. Characterization of trabecular bone plate-rod microarchitecture using multirow detector CT and the tensor scale: Algorithms, validation, and applications to pilot human studies. Med Phys. 2015 Sep;42(9):5410-25. doi: 10.1118/1.4928481.
• Chen C, Zhang X, Guo J, Jin D, Letuchy EM, Burns TL, Levy SM, Hoffman EA, Saha PK. Quantitative imaging of peripheral trabecular bone microarchitecture using MDCT. Med Phys. 2018 Jan;45(1):236-249. doi: 10.1002/mp.12632. Epub 2017 Nov 23.
• Rosen CJ, Bouxsein ML. Mechanisms of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol. 2006 Jan;2(1):35-43. doi: 10.1038/ncprheum0070.
• Bredella MA, Gill CM, Gerweck AV, Landa MG, Kumar V, Daley SM, Torriani M, Miller KK. Ectopic and serum lipid levels are positively associated with bone marrow fat in obesity. Radiology. 2013 Nov;269(2):534-41. doi: 10.1148/radiol.13130375. Epub 2013 Jul 16.
• Bredella MA, Daley SM, Kalra MK, Brown JK, Miller KK, Torriani M. Marrow Adipose Tissue Quantification of the Lumbar Spine by Using Dual-Energy CT and Single-Voxel (1)H MR Spectroscopy: A Feasibility Study. Radiology. 2015 Oct;277(1):230-5. doi: 10.1148/radiol.2015142876. Epub 2015 May 19.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Corticosteroid; Glucocorticoid
• Additional Relevant MeSH Terms: Metabolic Diseases; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Musculoskeletal Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Bone Diseases; Asthma; Bone Diseases, Metabolic
• Other Study ID Numbers: 202009045

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
• product manufactured in and exported from the U.S.: No