Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia

Osteopenia Clinical Trial

— ACAROS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02731820
• Other study ID #: 6013_IOR
• Secondary ID: 1676
• Status: Completed
• Phase: N/A
• Start date: September 1, 2015
• Est. completion date: September 30, 2017

Study information

• Verified date: October 2019
• Source: Istituto Ortopedico Rizzoli
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 30, 2017
• Est. primary completion date: August 30, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Disease, Metabolic
• Bone Diseases
• Bone Diseases, Metabolic
• Metabolic Diseases
• Osteopenia

Intervention

Dietary Supplement:
• Potassium citrate
Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
• Placebo
Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
• Vitamin D3
400 IU/die Vitamin D3 daily by mouth
• Calcium carbonate
500 mg/die calcium carbonate daily by mouth

Locations

Country	Name	City	State
Italy	Istituto Ortopedico Rizzoli	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Arnett TR. Acidosis, hypoxia and bone. Arch Biochem Biophys. 2010 Nov 1;503(1):103-9. doi: 10.1016/j.abb.2010.07.021. Epub 2010 Jul 23. Review. — View Citation

Granchi D, Caudarella R, Ripamonti C, Spinnato P, Bazzocchi A, Massa A, Baldini N. Potassium Citrate Supplementation Decreases the Biochemical Markers of Bone Loss in a Group of Osteopenic Women: The Results of a Randomized, Double-Blind, Placebo-Controll — View Citation

Hanley DA, Whiting SJ. Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet? J Clin Densitom. 2013 Oct-Dec;16(4):420-5. doi: 10.1016/j.jocd.2013.08.014. Epub 2013 Oct 2. Review. — View Citation

Jehle S, Hulter HN, Krapf R. Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2013 Jan;98(1):207-17. doi: 10.1210/jc.2012-3099. Epub 2012 Nov 15. — View Citation

Lambert H, Frassetto L, Moore JB, Torgerson D, Gannon R, Burckhardt P, Lanham-New S. The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis. Osteoporos Int. 2015 Apr;26(4):1311-8. doi: 10.1007/s00198-014-3006-9. Epub 2015 Jan 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)

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