Effect of n-3 polyunsaturated fatty acid on bone health: A systematic review and meta-analysis of randomized controlled trials

Bone metabolism is a complicated process, which involves bone modeling and remodeling. If this process is unbalanced, bone loss and resultant osteoporosis might occur. Recently, nutrition supplementations such as n-3 polyunsaturated fatty acids (PUFAs) are considered to be used on improving the bone metabolism and reducing the risk of osteoporosis. To more precisely assess the effects of n-3 PUFA supplementation on bone mass and clarify its potential mechanism, we have conducted a systematic review and meta-analysis. Based on the strict inclusion and exclusion criteria, 12 articles were included in this meta-analysis. The results in articles show that n-3 PUFAs could slightly enhance the level of bone mineral density (BMD) (0.005 g/cm²; 95% CI, 0.000-0.010) (n = 7), which was the primary outcome for the research in comparison with the control group. In addition, the results also illustrate that the increasing effect on BMD (0.024 g/cm²; 95% CI, 0.020-0.028) became more significant for postmenopausal women. N-3 PUFAs had no significance on the level of bone-specific alkaline phosphatase (BALP) (-0.24 µg/L; 95% CI, -0.86 to 0.39) and osteocalcin (-0.63 μg/L; 95% CI, -1.84 to 0.57) (n = 5), which are the specific markers of bone formation. When compared with the eicosapentaenoic acid + docosahexaenoic acid supplementation, the supplementation form of α-linolenic acid significantly increased the content of BALP (0.396 µg/L; 95% CI, 0.069-0.724). The effects of n-3 PUFAs on bone resorption biomarkers containing type I collagen cross-linked C-terminal peptide (CTX) and type I collagen cross-linked N-terminal peptide (NTX) are considered and used in our study. Results indicated that participants who received n-3 PUFAs significantly decreased the level of CTX in the human body (-0.367 μg/L; 95% CI, -0.726 to -0.007) (n = 4). However, there was no significant difference in NTX levels in humans after supplementation with n-3 PUFA (-1.744 µg/L; 95% CI, -3.970-0.481) (n = 3). For postmenopausal women, it presented a significant decreasing level of CTX (-0.393 µg/L; 95% CI, -0.651 to -0.135) and NTX (-2.082 µg/L; 95% CI, -2.970 to -1.195) within their bodies. In conclusion, these findings suggested that n-3 PUFAs might have a beneficial effect on bone health, especially for α-linolenic acid supplementation form or for postmenopausal women.