Contribution of Bone to Urine Citrate

NCT06811363 | Enrolling By Invitation

• 1 other identifier: STU-2024-0760
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Identification of the mechanisms by which bone contributes to urine citrate could lead to alternative explanations for and approaches to hypocitraturia. This proposal to explore the role of bone in urine citrate addresses the mission of the CMMCR to discover new mechanisms and innovative therapies for diseases of mineral metabolism. The results will be used to apply for extramural funding to further examine the nonrenal regulation of UCit. Hypothesis: Serum citrate is a function of bone citrate formation dependent on both bone mass and bone turnover. 20 subjects with osteoporosis naïve to treatment will be identified to examine bone parameters that correlate with ΔUcit/Δk. Use of potent anti-osteoporotic therapies to increase the likelihood of identifying significant bone turnover and BMD correlations with ΔUcit/Uk will take place in this study. Plan to achieve the following aim:

1. 1.Bone turnover marker at baseline
2. 2.BMD at baseline
3. 3.Change in bone turnover markers at 1 month and 6 months with each osteoporosis treatment modality (anti-resorptive agents such as Zoledronic acid or Denosumab, or the Anabolic agent Romosozumab)
4. 4.Change in bone mineral density at 6 with each osteoporosis treatment modality (anti-resorptive agents such as Zoledronic acid or Denosumab, or the Anabolic agent Romosozumab)

Conditions

Osteoporosis

Keywords

naïve to treatment; bone mass; bone turnover

Outcome Measures

Primary Outcomes (5)

• Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 1 month after initiating treatment

  Change in Urine Citrate levels to change in Potassium levels from the 24h urine samples is measured and will be correlated with baseline and post treatment bone turnover markers by multiple linear regression modeling using forward and backward selection.

  Baseline, 1month after initiating treatment

• Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 6 months after initiating treatment

  Change in Urine Citrate levels to change in Potassium levels from the 24h urine samples is measured and will be correlated with baseline and post treatment bone turnover markers by multiple linear regression modeling using forward and backward selection.

  Baseline, 6 months after initiating treatment

• Correlation of change in Urine Citrate levels to change in Potassium levels with bone densitometry at baseline

  Change in Urine Citrate levels to change in Potassium levels will be correlated with bone densitometry at lumbar spine, right hip, and radius

  Baseline

• Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone densitometry at 6 months after initiating treatment

  Change in Urine Citrate levels to change in Potassium levels will be correlated with change in bone densitometry at lumbar spine, right hip, and radius

  Baseline, 6 months after initiating treatment

• K Cit load

  The AUC for citrate will be calculated from the serum and urine levels based on the assumption that oral K Cit is 100% absorbed to estimate hepatic uptake effect on filtered load. The fractional excretion of citrate (FeCit) will be calculated from hourly serum and urine creatinine and citrate levels (FeCit = (serum Cit x Urine Cr)/urine Cit x serum Cr) x 100. Differences in FeCit will be correlated with ΔUcit/Δk and will be used to discriminate changes in ΔUcit/Δk due to filtered load vs renal handling.

  Predose, 0.5, 1, 2, 3, 4 hours after drug administration in Phases 1, 2, 3

Study Arms (2)

Anti-resorptive agents use Group

Patients with osteoporosis naïve to treatment will initiate treatment with anti-resorptive agents (zoledronic acid or denosumab)

Other: Metabolic / prescribed diet; Other: KCit Load (40 meq); Drug: Anti-resorptive agents

Anabolic agents use Group

Patients with osteoporosis naïve to treatment will initiate treatment with anabolic agents (romosozumab)

Other: Metabolic / prescribed diet; Other: KCit Load (40 meq); Drug: Anabolic Agents

Interventions

Metabolic / prescribed diet OTHER

Instructed diet (400 mg Ca, 800 mg P, 100 mEq Na) and two liters of distilled water daily for three days (equilibration period), followed by a constant standardized meal with the same composition of Ca, P, and Na for one day. After 240hr urine sample collection patient fasted the preceding evening except for 300 ml of distilled water at 9 pm and 11 pm. On test days, 600 ml distilled water given and fasting blood obtained.

Anabolic agents use Group; Anti-resorptive agents use Group

KCit Load (40 meq) OTHER

Potassium citrate load of 40meq will be given after fasting blood has been obtained

Anabolic agents use Group; Anti-resorptive agents use Group

Anti-resorptive agents DRUG

Zoledronic acid or Denosumab (as prescribed by their physician)

Anti-resorptive agents use Group

Anabolic Agents DRUG

Romosozumab (as prescribed by their physician)

Anabolic agents use Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with osteoporosis

You may qualify if:

• Osteoporosis naïve to treatment

You may not qualify if:

• eGFR \< 60 ml/min
• chronic diarrhea or gastrointestinal illness

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

Metabolic Networks and Pathways; Anabolic Agents

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Metabolism; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Eleanor Lederer, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: February 6, 2025
• Study Start: February 28, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. After 36 months the data will be available in the University's data warehouse but without investigator support other than deposited metadata.

Locations

US (1)