The Impact of Glomerular Disorders on Bone Quality and Strength

Recruiting

• Conditions: Bone Diseases, Metabolic; Bone Fracture; Glomerular Disease
• Interventions: Radiation: Dual-energy X-ray absorptiometry; Radiation: High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT); Other: Blood draw and Urine collection; Other: Questionnaires

• Registration Number: NCT04528446
• Lead Sponsor: Columbia University

Brief Summary

The primary objectives of this study are to: (1) determine the impact of glomerular disease on bone strength and (2) investigate the pathophysiologic underpinnings of impaired bone strength in glomerular disease.

Detailed Description

Children and adults with glomerular disease have unique and potentially modifiable risk factors for compromised bone health, but our current understanding of skeletal fragility in glomerular disease is lacking. In the first large population-based cohort study, we recently found that primary glomerular disease was independently associated with an increased risk of incident fracture, and that hip fracture risk was \>2-fold greater in patients younger vs. older than 40 years of age. Mechanisms that drive increased fracture risk in glomerular disease are not clear but likely multifactorial. Our prior work demonstrated that glomerular disease is associated with disturbances in vitamin D and mineral metabolism, in addition to and exacerbated by reduced kidney function.

Patients with glomerular disease are also exposed to medications which may negatively impact bone health, most notably high-dose and long-term glucocorticoid therapy. Identifying modifiable factors that compromise bone strength will facilitate the development of strategies to reduce fractures and other skeletal complications across the life course. The proposed multi-center study will leverage the infrastructure of the NIH-funded Cure Glomerulopathy (CureGN) prospective cohort study and the resources of two health systems with expertise in state-of-the-art high-resolution bone imaging methods, to conduct the first prospective, longitudinal study to assess determinants of impaired bone quality and strength in glomerular disease.

Study Timeline

• Study Start: 2019-06-14
• Study First Submitted: 2020-08-24
• Study First Submitted QC: 2020-08-24
• Study First Posted: 2020-08-27
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-28
• Last Update Posted: 2024-07-01
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
BoneGN participants	High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)	Participants who have already been recruited into the CureGN study, or meet its criteria.
BoneGN participants	Dual-energy X-ray absorptiometry	Participants who have already been recruited into the CureGN study, or meet its criteria.
BoneGN participants	Blood draw and Urine collection	Participants who have already been recruited into the CureGN study, or meet its criteria.
BoneGN participants	Questionnaires	Participants who have already been recruited into the CureGN study, or meet its criteria.

Primary Outcome Measures

Name	Time	Method
Change in radius bone strength (failure load)	Baseline and 12 months	HR-pQCT will be used to assess bone microarchitecture and generate micro-finite element analysis (µFEA)-based estimates of bone strength.
Change in tibia bone strength (failure load)	Baseline and 12 months	HR-pQCT will be used to assess bone microarchitecture and generate micro-finite element analysis (µFEA)-based estimates of bone strength.

Secondary Outcome Measures

Name	Time	Method
Cortical density of radius	Up to 12 months	Measured with HR-pQCT
Tibia mid-shaft failure load	Up to 12 months	Measured with HR-pQCT
Areal bone mineral density (aBMD) at the hip	Up to 12 months	Hip (total and femoral neck) is measured with dual-energy x-ray absorptiometry (DXA)
aBMD at lumbar spine	Up to 12 months	Lumbar spine is measured with DXA
aBMD at forearm	Up to 12 months	Forearm (one-third and ultradistal radius) is measured with DXA
Bone mineral content at the hip	Up to 12 months	Hip (total and femoral neck) is measured with dual-energy x-ray absorptiometry (DXA)
Radius mid-shaft failure load	Up to 12 months	Measured with HR-pQCT
Cortical density of tibia	Up to 12 months	Measured with HR-pQCT
Cortical thickness of tibia	Up to 12 months	Measured with HR-pQCT
Cortical thickness of radius	Up to 12 months	Measured with HR-pQCT
Bone mineral content at forearm	Up to 12 months	Forearm (one-third and ultradistal radius) is measured with DXA
Bone mineral content at lumbar spine	Up to 12 months	Lumbar spine is measured with DXA

Trial Locations

Locations (2)

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States