The Impact of Glomerular Disorders on Bone Quality and Strength

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.

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.

Eligibility Criteria:
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.