Lower Serum Bicarbonate Associated with Lower BMD

In a cohort of adults in the United States, lower serum bicarbonate levels were associated with lower bone mineral density (BMD) in a study conducted recently by Wei Chen, MD, and colleagues. The researchers reported their results in the American Journal of Kidney Diseases [2015;65(2):240-248].

Chronic kidney disease can cause chronic metabolic acidosis, which has a negative effect on bone, inducing bone resorption and inhibiting bone formation, resulting in lower total BMD. There is evidence of a clinically meaningful low-level metabolic acidosis in otherwise healthy individuals, largely mediated by the age-related decline in kidney function and the acidogenic Western diet. The effect of low-level metabolic acidosis on bone metabolism in the general population is not known.

This cross-sectional study was designed to test the hypothesis that the association between serum bicarbonate levels and BMD may differ between the sexes. The study utilized data on adults ≥20 years of age who underwent dual-energy x-ray absorptiometry (DEXA) in NHANES (National Health and Nutrition Examination Survey) from 1999 to 2004.

The study outcomes were lumbar and total BMD, as well as low lumbar and total bone mass, defined as 1.0 SD below the sex-specific mean value of young adults. BMD was measured by dual-energy x-ray absorptiometry; serum bicarbonate was measured in all study participants.

The analysis included 9724 individuals. Of those, 48.8% were women, and mean serum bicarbonate level was 24.9 mEq/L. Serum bicarbonate levels were higher in men than in women (25.2 vs 24.5 mEq/L; P<.001), a difference that persisted in multivariable analysis including adjustment for net endogenous acid production.

Men and women with lower serum bicarbonate levels were more likely to be current smokers and have higher body mass index and estimated net endogenous acid production. Men who had lower serum bicarbonate levels received less education and were less likely to use diuretics. They were also more likely to have diabetes mellitus, hypertension, cardiovascular disease, or albuminuria.

Women with lower serum bicarbonate levels were more likely to be younger, have greater poverty, and higher estimated glomerular filtration rates, and were less likely to be non-Hispanic white, to have fasted ≤2 hours prior to phlebotomy, or to have used diuretics or calcium carbonate. They were also less likely to have diabetes mellitus, hypertension, or cardiovascular disease, in contrast to men.

There was a statistically significant association of lumbar or total BMD across quartiles in women but not men in bivariate analysis. There were 1673 women (36.1%) and 1290 men (25.3%) with either low lumbar or low total bone mass.

In multivariable linear regression models, there was a significant linear trend across quartiles of serum bicarbonate with lumbar BMD among the total population, and in sex-specific models; P=.02 for all three models; P=.01 for interaction).

Compared to the reference group, women with bicarbonate levels of 24 to 25, 25.1 to 26.9, or ≥27 mEq/L had higher lumbar BMDs (0.015 [95% confidence interval (CI), 0.002-0.028], 0.016 [95% CI, 0.003-0.030], and 0.019 [95% CI, 0.003-0.036] g/cm2, respectively).

For total BMD, there was no statistically significant association with serum bicarbonate level in the total population or for men. For women, there was a significant association between serum bicarbonate level and total BMD (P=.02). There was no statistically significant association of serum bicarbonate level with low lumbar BMD in either men or women. There was a significant association of serum bicarbonate level with low total bone mass in women.

There were 2805 women with known menopausal status; there was a linear trend in association between serum bicarbonate levels and lumbar BMD among both pre- and postmenopausal women (P=.04 and P=.02, respectively). For total BMD, there was a statistically significant association among postmenopausal women (P=.02), but not among premenopausal women. Among postmenopausal women, compared with those with serum bicarbonate levels <24 mEq/L, those with serum bicarbonate levels ≥27 mEq/L had 0.024 g/cm2 higher total BMD (P=.01).

The researchers cited the cross-sectional design of the study and using a single measurement of serum bicarbonate as limitations to the study. In addition, subgroup differences were not definitive.

“In conclusion, we have shown that lower serum bicarbonate levels were associated with lower lumbar and total BMD in US adults. Further studies are warranted to illuminate the determinants of serum bicarbonate levels in people without kidney disease and investigate whether serum bicarbonate levels should be incorporated into the diagnostic assessment guidelines or management of osteoporosis,” the researchers said.


Takeaway Points

  1. The effect of low-level metabolic acidosis on bone metabolism in the general population is not known. This cross-sectional study was designed to test the hypothesis that the association between serum bicarbonate levels and BMD may differ between the sexes.
  2. The study outcomes were lumbar and total BMD, as well as low lumbar and total bone mass, defined as 1.0 SD below the sex-specific mean value of young adults.
  3. Lower serum bicarbonate levels were associated with lower lumbar and total BMD in US adults.