Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether the use of alkali compounds, i.e. potassium citrate (K3C6H5O7, hereinafter KCitr) is effective in preventing the progression of osteopenia. A randomized clinical trial (RCT, placebo-controlled, double-blind) has been planned to evaluate the effect of the daily administration of KCitr (3 g/die, K 30 mEq). The efficacy will be evaluated by comparing the circulating levels of bone turnover markers at the baseline and after the treatment (3, 6 months).

Detailed Description
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Bone tissue carries out some of the important metabolic functions, including the regulation of acid-base balance. In order to buffer the systemic acidosis, the skeleton acts as a ion exchange column modifying the composition of the mineral portion, i.e. the hydroxyapatite. There is a linear correlation between elimination of calcium and acidosis: the higher is the acidosis, the higher will be the loss of calcium from bones. In vitro experiments showed that acidosis also directly influences the cellular component of bone by increasing the osteoclast activity and inhibiting the production of the mineralized matrix by osteoblast. Since the low pH is a risk factor that accelerates the bone loss, the use of alkalizing compounds could prevent the osteopenia or support the conventional therapy of the osteoporosis. KCitr is an alkaline compound which may be used in metabolic acidosis. Potassium is an alkaline metal that plays a pivotal role in the function of all living cells. Citric acid is a key molecule of the Krebs cycle, and it is abundant in bone where exhibits a stabilizing function. Although clinical data regarding the KCitr effectiveness on calcium metabolism are encouraging, it is still unclear whether the beneficial effects are due exclusively to the buffering function or whether KCitr may affect the bone cells activity. The purpose of this study is to evaluate the effects of KCitr on bone metabolism. We hypothesize that administration of potassium citrate to postmenopausal women with osteopenia will delay (or will prevent) the weakening of bone mass. Postmenopausal women with osteopenia (T score between -1.0 and -2.5) and no history of fracture will be randomized to assume KCitr ate or placebo, daily for six months. Primary outcomes will be evaluated by measuring markers of bone turnover, which will be measured at baseline (before treatment), in the mid-term (3 months) and at the end (6 months).

Official Title
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Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia. A Randomized, Placebo-controlled, Double Blind Investigation.

Conditions
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Osteopenia, Bone Disease, Metabolic

Intervention / Treatment
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* Dietary Supplement: Potassium citrate
* Dietary Supplement: Placebo
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Calcium carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women, more than 5 years post menopause Osteopenia (T-score < -1 and > -2.5) Low risk of fracture (FRAX: < 20 major osteoporotic; < 3 hip fracture) Exclusion Criteria: Hyperkalemia Renal insufficiency Nephrolithiasis Use of potassium sparing diuretics Use of potassium supplements Use of therapies influencing bone metabolism (e.g. corticosteroids, thiazide diuretics, aromatase inhibitors, estrogens) Use of protonic pump inhibitors Current or recent use of bisphosphonates (stopped less than three years prior to the start of the study) Gastrointestinal disorders that hamper nutrient absorption; Mental or psychiatric disorders that preclude the possibility of correctly adhering to the protocol
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Potassium citrate Calcium carbonate Vitamin D3 | Dietary Supplement: Potassium citrate<br>* Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)<br>Dietary Supplement: Vitamin D3<br>* 400 IU/die Vitamin D3 daily by mouth<br>* Other names: Cholecalciferol;Dietary Supplement: Calcium carbonate<br>* 500 mg/die calcium carbonate daily by mouth<br>|
| Placebo Comparator: Control group, Placebo<br>Placebo (Excipients) Calcium carbonate Vitamin D3 | Dietary Supplement: Placebo<br>* Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)<br>Dietary Supplement: Vitamin D3<br>* 400 IU/die Vitamin D3 daily by mouth<br>* Other names: Cholecalciferol;Dietary Supplement: Calcium carbonate<br>* 500 mg/die calcium carbonate daily by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | Carboxyterminal cross-linked telopeptide of type I collagen (CTX) is a degradation product of the type I collagen; it is considered as a marker of bone resorption. The concentration of CTX (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value <0.05. | Baseline (T0), 3 months (T3) 6 months (T6) | 
| Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | Tartrate-resistant acid phosphatase 5b isoenzyme (TRAcP5b) is a specific product of osteoclasts; it is considered as a marker of bone resorption. The concentration of TRAcP5B (U/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium Citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value <0.05. | Baseline (T0), 3 months (T3) 6 months (T6) | 
| Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | N-terminal propeptide of type I procollagen (P1NP) is a product of the conversion of procollagen to collagen; it is considered as a marker of bone formation. The concentration of P1NP (pg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value <0.05. | Baseline (T0), 3 months (T3) 6 months (T6) | 
| Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Bone-specific alkaline phosphatase (BAP) is a specific product of osteoblasts; it is considered as a marker of bone formation. The concentration of BAP (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value <0.05. | Baseline (T0), 3 months (T3) 6 months (T6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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potassium citrate