Contribution of Bone to Urine Citrate

NCT ID: NCT06811363

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

25 participants

Study Classification

OBSERVATIONAL

Study Start Date

2026-01-31

Study Completion Date

2026-03-31

Brief Summary

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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:

* Correlate ∆ Ucit/∆k in response to acute KCit load with:

1. Bone turnover marker at baseline
2. BMD at baseline
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. 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)

Detailed Description

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Screening Visit: Before enrollment into the trial, potential candidates will undergo screening, whereby the study team will conduct a physical exam and ask questions about the subject's medical history, including medications and any surgical procedures. Those who meet the entry-exclusion criteria will be selected for consideration into the study. During screening, subjects will provide information on or have the following exams, tests or procedures:

* Social and medical history;
* Medications;
* Vital signs;
* Demographic information (age, gender, ethnic origin);
* Personal information (name, date of birth, address, telephone number, emergency contact, and referring physician)

Assignment to groups:

Group 1- Patients with osteoporosis naïve to treatment will initiate treatment with anti-resorptive agents (zoledronic acid or denosumab).

Group 2- - Patients with osteoporosis naïve to treatment will initiate treatment with anabolic agents (romosozumab).

The anti-osteoporosis medication would be prescribed by the treating physician.

Phase 1 (pre-treatment phase):

All patients will be stabilized with 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 (stabilization period) and undergo a run-in (pre-Rx) period.

One 24-hour urine will be obtained on day 4 without mineral oil (stabilization period). The 24-hour urine will be analyzed for total volume, pH, creatinine, sodium, potassium, calcium, magnesium, phosphorus chloride, oxalate, citrate, ammonium, titratable acidity, bicarbonate and deoxypyridinoline (DPD). The patient will be fasted from 9 pm of the preceding evening except for 300 ml of distilled water at 9 pm and 11 pm. On test days, 600 ml of distilled water will be given at 7 am and fasting blood will be obtained tested for Serum BMP, citrate and bone turnover markers (CTX, P1NP, bone alkaline phosphatase).

Potassium citrate load of 40meq will be given after fasting blood has been obtained and hourly blood and urine measurements of citrate and creatinine for 4 hours after ingesting will be collected.

Laboratory Analysis:

Urine samples - Post-load every 1 hour for 4 hours analyzed for citrate and creatinine by Mineral Metabolism Laboratory.

Blood samples - Post-load every 1 hour for 4 hours analyzed for citrate and creatinine by Mineral Metabolism Laboratory.

Phase 2 (1 month after initiating treatment) and Phase 3 (6 months after initiating treatment):

These two visits consist of identical study procedure as Phase 1.

Imaging:

Imagining studies will be done using DXA for bone density measurement and micro-CT measurement for determaination of bone quality and microarchitecture of the bone. The imaging studies will be performed during phase 1 and phase 3.

Conditions

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Osteoporosis

Keywords

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naïve to treatment bone mass bone turnover

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Anti-resorptive agents use Group

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

Metabolic / prescribed diet

Intervention Type 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.

KCit Load (40 meq)

Intervention Type OTHER

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

Anti-resorptive agents

Intervention Type DRUG

Zoledronic acid or Denosumab (as prescribed by their physician)

Anabolic agents use Group

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

Metabolic / prescribed diet

Intervention Type 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.

KCit Load (40 meq)

Intervention Type OTHER

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

Anabolic Agents

Intervention Type DRUG

Romosozumab (as prescribed by their physician)

Interventions

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Metabolic / prescribed diet

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.

Intervention Type OTHER

KCit Load (40 meq)

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

Intervention Type OTHER

Anti-resorptive agents

Zoledronic acid or Denosumab (as prescribed by their physician)

Intervention Type DRUG

Anabolic Agents

Romosozumab (as prescribed by their physician)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Osteoporosis naïve to treatment

Exclusion Criteria

* eGFR \< 60 ml/min
* chronic diarrhea or gastrointestinal illness
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Eleanor Lederer

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Eleanor Lederer, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Central Contacts

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Eleanor Lederer, M.D.

Role: CONTACT

Phone: 214/645-3534

Email: [email protected]

Naim Maalouf, M.D.

Role: CONTACT

Phone: 214/648-2954

Email: [email protected]

Other Identifiers

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STU-2024-0760

Identifier Type: -

Identifier Source: org_study_id