Glomerular Disease, Bone Diseases, Metabolic, Bone Fracture
Conditions
Keywords
Kidney Disease, Bone Fracture
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.
Interventions
RADIATIONDual-energy X-ray absorptiometry
DXA whole body, hip, spine, and radius at baseline, and 12-month visit.
RADIATIONHigh Resolution Peripheral Quantitative Computed Tomography (HR-pQCT)
HR-pQCT of the radius and tibia at baseline, and 12-month visit.
The blood draw can be completed +/- 3 weeks from baseline or 12-month visit.
OTHERQuestionnaires
Questionnaires regarding fracture history, physical activity and dietary intake at baseline, and 12-month visit.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Columbia University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
5 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
for participants with glomerular disease: 1. CureGN participant or CureGN Eligible CureGN eligible is defined as having a diagnosis of Glomerulonephropathy (GN). Patients would otherwise be enrolled in be in CureGN study, except for lacking a minor entry criteria, such as: 1. First diagnostic kidney biopsy within 5 years of CureGN study enrollment 2. Access to first kidney biopsy report and/or slides or not being interested in study participation. 2. Males or females 5 to 55 years (premenopausal for women) 3. Females must have a negative urine/serum pregnancy test 4. Stable doses of nutritional vitamin D or active vitamin D therapy for at least 3 months before enrollment ((if on either form of Vitamin D) 5. Consent/Parental/guardian permission (informed consent) and if appropriate, child assent
Exclusion criteria
for all participants 1. Chronic Dialysis 2. Solid organ transplantation 3. Lower extremity amputations or non-ambulatory 4. Malignancy requiring chemotherapy or metastatic to bone 5. Metabolic bone disease (e.g., Paget's disease, primary hyperparathyroidism) 6. Endocrinopathy (current hyperthyroidism or untreated hypothyroidism, Cushing's syndrome) 7. Medical diseases (end stage liver disease, heart or lung disease, intestinal malabsorption) 8. Those treated with bisphosphonates, teriparatide, calcitonin, selective estrogen receptor modulators, estrogen, or phenytoin in the past 12 months 9. Previous bilateral wrist and tibia fractures 10. Pregnant or lactating females 11. Parents/guardians or participants who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cortical density of radius | Up to 12 months | Measured with HR-pQCT |
| Cortical density of tibia | Up to 12 months | Measured with HR-pQCT |
| Cortical thickness of radius | Up to 12 months | Measured with HR-pQCT |
| Cortical thickness of tibia | 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) |
| Radius mid-shaft failure load | Up to 12 months | Measured with HR-pQCT |
| aBMD at lumbar spine | Up to 12 months | Lumbar spine 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) |
| 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 |
| aBMD at forearm | Up to 12 months | Forearm (one-third and ultradistal radius) is measured with DXA |
| Tibia mid-shaft failure load | Up to 12 months | Measured with HR-pQCT |
Countries
United States
Contacts
Primary ContactMaria A. Aponte
Backup ContactThomas L. Nickolas, MD
Outcome results
None listed