Clinical trial NCT06811363: Contribution of Bone to Urine Citrate
Official title: Contribution of Bone to Urine Citrate
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Osteoporosis
Keywords: naïve to treatment
bone mass
bone turnover
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2025-02-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with osteoporosis

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:

* 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: 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.

Eligibility criteria: Inclusion Criteria:

* Osteoporosis naïve to treatment

Exclusion Criteria:

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

Primary outcomes:
measure: Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 1 month after initiating treatment
timeFrame: Baseline, 1month after initiating treatment
measure: Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone turnover markers at 6 months after initiating treatment
timeFrame: Baseline, 6 months after initiating treatment
measure: Correlation of change in Urine Citrate levels to change in Potassium levels with bone densitometry at baseline
timeFrame: Baseline
measure: Correlation of change in Urine Citrate levels to change in Potassium levels with change in bone densitometry at 6 months after initiating treatment
timeFrame: Baseline, 6 months after initiating treatment
measure: K Cit load
timeFrame: Predose, 0.5, 1, 2, 3, 4 hours after drug administration in Phases 1, 2, 3
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: UT Southwestern Medical Center
name: Eleanor Lederer, MD
role: PRINCIPAL_INVESTIGATOR
References: