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

Abstract

The relationship involving acid-base imbalance, mineral metabolism and bone health status has previously been reported but the efficacy of the alkalizing supplementation in targeting acid overload and preventing bone loss has not yet been fully elucidated. In this randomized, double-blind, placebo-controlled study, the hypothesis that potassium citrate (K citrate) modifies bone turnover in women with postmenopausal osteopenia was tested. Three hundred and ten women were screened; 40 women met the inclusion criteria and were randomly assigned to the treatment or the placebo group. They were treated with K citrate (30 mEq day−1) or a placebo in addition to calcium carbonate (500 mg day−1) and vitamin D (400 IU day−1). At baseline and time points of 3 and 6 months, serum indicators of renal function, electrolytes, calciotropic hormones, serum bone turnover markers (BTMs) (tartrate-resistant acid phosphatase 5b (TRACP5b), carboxy-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (BAP), procollagen type 1 N terminal propeptide (PINP)), and urine pH, electrolytes, and citrate were measured. The follow-up was completed by 17/20 patients in the “K citrate” group and 18/20 patients in the “placebo” group. At baseline, 90% of the patients exhibited low potassium excretion in 24 h urine samples, and 85% of cases had at least one urine parameter associated with low-grade acidosis (low pH, low citrate excretion). After treatment, CTX and BAP decreased significantly in both groups, but subjects with evidence of low-grade acidosis gained significant benefits from the treatment compared to the placebo. In patients with low 24h-citrate excretion at baseline, a 30% mean decrease in BAP and CTX was observed at 6 months. A significant reduction was also evident when low citrate (BAP: −25%; CTX: −35%) and a low pH (BAP: −25%; CTX: −30%) were found in fasting-morning urine. In conclusion, our results suggested that K citrate supplementation improved the beneficial effects of calcium and vitamin D in osteopenic women with a documented potassium and citrate deficit, and a metabolic profile consistent with low-grade acidosis.

Role of Citrate in Pathophysiology and Medical Management of Bone Diseases

“…Similarly, the MSC differentiation towards adipocytes requires more citrate as a source of cytosolic acetylCoA for lipid biosynthesis [85]. In conclusion, according to Granchi et al, estrogen deficiency leads to a “net citrate loss” which could explain the diminished citrate excretion observed in postmenopausal women [91].…”

“…Additional findings regarding potassiun citrate can be summarised as follows: effectiveness may be enhanced by combined treatment with calcium citrate [139]; positive effects have also been observed in young women and in the absence of an excessive acid load [140]. Moreover, supplementation with alkalising potassium citrate improved the beneficial effects of calcium and vitamin D only in osteopenic postmenopausal women who exhibited the target conditions, namely low potassium and/or citrate excretion and/or low urine pH [91]. Finally, one study questioned the beneficial effects of potassium citrate since, at 24 months, no significant modifications in BTMs and BMD were recorded [134].…”

Citrate Supplementation Restores the Impaired Mineralisation Resulting from the Acidic Microenvironment: An In Vitro Study

“…However, the numerous clinical trials did not consider in their rationale that citrate, by itself, plays an essential role in maintaining bone health, as proved by the previously cited experimental studies and also supported by clinical evidence. Low citrate excretion has been found in a considerable proportion of osteopenic women [ 16 ] and there is a strong relationship between urinary citrate excretion and the prevalence of fragility fracture in postmenopausal women [ 30 ]; plasma citrate levels correlate with the bone mineral density of the lumbar spine and hip [ 36 ]. By comparing the results obtained in this study with the results of interventional clinical trials, a “common ground” emerges.…”

“…Overall, in the clinical setting, an adequate calcium intake is fundamental for preventing bone loss; however, Ca citrate seems to be more effective than calcium carbonate [ 67 , 68 , 69 ]. Potassium citrate limits bone loss in postmenopausal women and elderly subjects, with or without osteoporosis [ 70 , 71 , 72 , 73 , 74 , 75 ] and also anabolic effects with increased circulating levels of bone formation markers, i.e., PINP, have been reported [ 16 , 74 ]; combined treatment K citrate and Ca citrate allows obtaining an additional decrease in bone turnover [ 76 ]. Finally, positive effects of citrate supplementation have also been observed in the absence of an excessive acid load [ 77 ].…”

“…For the above reasons, urinary citrate excretion has been proposed as a laboratory parameter for monitoring the acid–base balance and bone health status, even in subjects without overt metabolic acidosis [ 14 , 15 , 16 , 17 ]. Similarly, citrate-based supplements have been used as a possible strategy for treating medical conditions related to acid overload and poor citrate bioavailability, and for mitigating the detrimental effect on skeletal homeostasis.…”