The relationship between heavy metal exposure and risk of osteopenia or osteoporosis has biological plausibility, yet it remains inconclusive;​ therefore, we conducted a systematic review and meta-analysis to evaluate the associations between exposure to heavy metals (i.e., cadmium, lead, and mercury) and the risk of osteopenia or osteoporosis. Databases of MEDLINE, Embase, Scopus, and Web of Science were searched through November 2019, to identify studies that evaluated the relationship between exposure to cadmium, lead, and mercury and risk of osteopenia or osteoporosis in adults. Fourteen eligible studies were included. Effect sizes expressed as pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated using weighted random-effect models. Exposure to cadmium (OR = 1.35;​ 95% CI:​ 1.17 to 1.56;​ P ≤ 0.001) and lead (OR = 1.15;​ 95% CI:​ 1.00 to 1.32;​ P = 0.05) was associated with an increased risk of osteopenia or osteoporosis, unlike mercury. Subgroup analyses showed cadmium exposure increased the risk of osteopenia or osteoporosis in older (> 65 yrs.;​ OR = 1.43;​ 95%CI:​ 1.08 to 1.88, P = 0.01) compared with younger (18-65 yrs.;​ OR = 1.24;​ 95% CI:​ 1.02 to 1.52, P = 0.03) adults. Also, lead exposure increased the risk in men (OR = 1.55;​ 95% CI:​ 1.15 to 2.09, P = 0.007) unlike in women. By contrast to urinary levels, blood (OR = 1.26;​ 95% CI:​ 1.08 to 1.47, P = 0.003) and dietary (OR = 1.46;​ 95% CI:​ 1.28 to 1.67, P < 0.001) levels of cadmium were associated with an increased risk of osteopenia or osteoporosis. Exposure to cadmium and lead may be associated with an increased risk of osteopenia or osteoporosis, although high heterogeneity was detected.