Association of urinary citrate with acid-base status, bone resorption, and calcium excretion in older men and women

Authors: SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/28/2017
Publication Date: 12/1/2017
Citation: Shea, K., Dawson-Hughes, B. 2017. Association of urinary citrate with acid-base status, bone resorption, and calcium excretion in older men and women. Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/jc.2017-01778.

Interpretive Summary: Typical Western diets, which are high in protein and cereal grains (acid-producing foods) and low in fruits and vegetables (alkali-producing foods), promote mild increases in acid-load, which has been associated with increased bone turnover in older adults. Systemic acid load can be measured directly using 24-hour urine net acid excretion (NAE). NAE responds to changes in diet and correlates positively with bone turnover. However, measuring NAE is labor intensive, which makes it difficult to implement in large-scale studies. Urine citrate, which is measured routinely in many clinical laboratories, increases as acid-load decreases, but its association with bone turnover in older adults is uncertain. Therefore, we evaluated urine citrate as a potential alternate indicator of acid-load in relation to bone turnover in healthy adults age 60 years and older. We found urine citrate increased as acid-load decreased following alkali supplementation. However, the change in urine citrate was not consistently associated with change in bone turnover. The change in NAE was significantly associated with change in bone resorption and urine calcium excretion. These findings indicate urine citrate may not be a suitable alternative to NAE when assessing acid-base status in relation to bone turnover in older adults.

Technical Abstract: Context: Elevated urine net acid excretion (NAE), indicative of subclinical metabolic acidosis, has been associated with higher bone turnover. While NAE is the gold-standard clinical measure of acid-base status, it is impractical to measure in most clinical/research settings. Urine citrate, which is commonly measured, changes in response to acid-base status, but its association with bone turnover is uncertain. Objective: To evaluate the association between change in urine citrate and change in bone turnover and calcium excretion. Design, Intervention, Participants: 233 healthy men and women >/= 60 years were randomly assigned to 1.0 mmol/kg/day potassium bicarbonate (KHCO3), 1.5 mmol/kg/day KHCO3, or placebo for 84 days. Outcome measures: Urine citrate, NAE, N-telopeptide of collagen type-I (NTX), calcium excretion and serum amino-terminal-propeptide of type-1-procollagen (P1NP) were measured pre- and post-intervention. Results: Urine citrate increased dose-dependently following KHCO3 supplementation (p-trend<0.001). The urine citrate change was significantly inversely associated with P1NP change (p=0.021), but not with change in NTX (p=0.051) or calcium excretion (p=0.652). The change in NAE was positively associated with change in NTX and calcium excretion (p/=0.086), whereas change in NAE remained associated with change in NTX and calcium excretion (p