Clinical trial NCT02731820: Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia
Official title: Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia. A Randomized, Placebo-controlled, Double Blind Investigation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteopenia
Bone Disease, Metabolic
Keywords: potassium citrate
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2016-04-08
Enrollment: 40
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months.
timeFrame: Baseline (T0), 3 months (T3) 6 months (T6)
measure: Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months.
timeFrame: Baseline (T0), 3 months (T3) 6 months (T6)
measure: Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months.
timeFrame: Baseline (T0), 3 months (T3) 6 months (T6)
measure: Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months.
timeFrame: Baseline (T0), 3 months (T3) 6 months (T6)
Secondary outcomes:
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
Study officials:
affiliation: Istituto Ortopedico Rizzoli
name: Nicola Baldini, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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-Controlled Pilot Study. Nutrients. 2018 Sep 12;10(9):1293. doi: 10.3390/nu10091293.