Effect of Acid or Base Interventions on Bone Health: A Systematic Review, Meta-Analysis, and Meta-Regression

Osteoporosis is a global health issue among the aging population. The effect of the acid or base interventions on bone health remains controversial. This study performed a systematic review and meta-analysis to investigate effects of acidic diets and alkaline supplements on bone health simultaneously. We conducted a comprehensive literature search in 5 available databases and 1 registered clinical trial system to identify randomized controlled trials (RCTs) that assessed effects of the acid-base intervention on bone health. Depending on heterogeneity across studies, the pooled effects were calculated by fixed-effects or random-effects models. The present study included 13 acidic diet intervention studies and 13 alkaline supplement studies for final quantitative assessments. The meta-analysis showed that acidic diets significantly increased net acid excretion [NAE; standardized mean difference (SMD) = 2.99; P = 0.003] and urinary calcium excretion (SMD = 0.47, P < 0.00001) but had no significant effect on bone turnover markers and bone mineral density (BMD). On the other hand, alkaline supplement intervention significantly reduced NAE (SMD = -1.29, P < 0.00001), urinary calcium excretion (SMD = -0.44, P = 0.007), bone resorption marker aminoterminal cross-linking telopeptide (NTX; SMD = -0.29, P = 0.003), and bone formation marker osteocalcin (OC; SMD = -0.23, P = 0.02), but did not affect the other bone turnover markers. Furthermore, alkaline supplements significantly increased BMD in femoral neck [mean difference (MD) = 1.62, P < 0.00001, I2 = 0%], lumbar spine (MD = 1.66, P < 0.00001, I2 = 87%), and total hip (MD = 0.98, P = 0.02, I2 = 99%). Subsequently, meta-regression analyses identified 1 study that substantially contributed to the high heterogeneity of BMD in the latter 2 sites, but sensitivity analysis suggested that this study did not affect the significant pooled effects. Despite that, the results should be interpreted with caution and need to be further validated by a larger RCT. In summary, through integrating evidence from RCTs, the present meta-analysis initially suggests that alkaline supplements may be beneficial to bone metabolism and acidic diets may not be harmful to bone health. This work may be clinically useful for both clinicians and patients with osteoporosis.