Table 1.
Demographic characteristics, evaluation parameters, and outcomes of 15 observational studies.
| Author, Year, Location | Included to Meta-Analysis | Study Design | Total Population (Age as a Range or Mean ± SD) | Sex | BCX Exposure | Outcome Variables | Bias Variables Adjustment | Summary | Quality Rating † (Risk of Bias) |
|---|---|---|---|---|---|---|---|---|---|
| Regu, 2017, South Korea [14] | Yes | Cross-sectional | 8022 (age 30–74) | Male, pre-/postmenopausal female | Quintile of BCX intake (postmenopausal female): Q1 (0.0003–0.01 mg/day) Q2 (0.01–0.04 mg/day) Q3 (0.04–0.10 mg/day) Q4 (0.10–0.59 mg/day) Q5 (0.60–18.53 mg/day) |
Coefficient of BCX intake with the BMDs of femur neck, total hip, lumber spine, and whole body; odds ratios for femur neck, total hip, lumber spine, and total osteopenia. | Yes | On pre-menopausal women, BCX consumption was positively correlated with femur neck BMD and total hip BMD. BCX consumption was also positively correlated with total hip BMD. | Fair |
| Sugiura, 2011, Japan [15] | Yes | Cross-sectional | 293 (age 60.2 ± 6.2) | Postmenopausal female | Tertile of BCX intake Q1 (0.00–0.30 mg/day) Q2 (0.31–1.21 mg/day) Q3 (1.22–7.91 mg/day) |
Odds ratios for BMD | Yes | Higher daily intake of BCX significantly prevented the risk of osteoporosis. | Fair |
| Hayhoe, 2017, United Kingdom [16] | Yes | Prospective cohort (12.5 mean years) | Fracture analysis data, 25,566; ultrasound analysis data, 14,877 (age 39–79) | Male, pre-/postmenopausal female | Quintile of BCX intake, quintile of serum BCX concentration | Calcaneal broadband ultrasound attenuation (BUA); total fracture; hip fracture; spine fracture; wrist fracture | Yes | The amount of BCX intake is positively related to the higher BUA value in women. In men, the hip fracture risk was significantly lower in the 5th quintile as compared with the 1st quintile with a 0.65 hazard ratio. | Good |
| Dai, 2014, Singapore [21] | Yes | Prospective cohort (9.9 mean years) | 63154 (age 45–74) | Male, female | Quartile of BCX intake | Incidence of hip fracture | Yes | Intake of BCX was insignificant in reducing the risk of hip fracture in both males and females. | Good |
| Sahni, 2009 (2), United States [22] | Yes | Prospective cohort (17 years) | 929 (age 75 ± 5) | Male, pre-/postmenopausal female | Tertile of BCX intake | Hazard ratios for hip fracture | Yes | There was an absence of evidence that the intake of BCX plays a role in the reduction of the risk of hip fracture. | Fair |
| Liu, 2018, China [23] | Yes | Case-control | Case, 196 (age 44.0–60.0); control, 196 (age 43.2–60.0) | Male, pre-/postmenopausal female | Quartile of BCX intake (mean value): Q1 (0.0762 mg/day) Q2 (0.1589 mg/day) Q3 (0.3139 mg/day) Q4 (0.8341 mg/day) |
Odds ratios for skeletal fluorosis | Yes | Intake of BCX was ineffective in reducing the risk of skeletal fluorosis. | Fair |
| Cao, 2018, China [24] | Yes | Case-control | Case, 1070 (age 52–83); control, 1070 (age 52–83) | Male, postmenopausal female | Quartile of BCX intake (mean value): Q1 (0.030–0.031 mg/day) Q2 (0.063–0.064 mg/day) Q3 (0.096–0.097 mg/day) Q4 (0.151–0.164 mg/day) |
Odds ratios for hip fracture | Yes | The highest consumption quartile of BCX showed significantly reduced odd ratios on hip fractures. Subgroup analysis by gender revealed a corresponding result in terms of reducing hip fracture risk. | Good |
| Zhang, 2016, China [25] | No | Prospective cohort (3.1 mean years) | 2831 (age 50–75) | Male, postmenopausal female | Quartile of serum BCX concentration | BMD of the whole body, hip (total), femur neck, trochanter, intertrochanter | Yes | The serum level of BCX was positively correlated to the higher value of lumber spine and femur neck BMD in postmenopausal women. | Fair |
| Sugiura, 2016, Japan [26] | No | Prospective cohort (4 years) | 187 (age 60.5 ± 5.8) | Postmenopausal female | Low (0.24–1.84 μM) or high (1.88–10.53 μM) level of serum BCX concentration | Odds ratios for osteoporosis | Yes | The higher serum concentration of BCX with a higher intake of Vitamin C showed a significantly reduced risk of osteoporosis compared to the lower serum concentration of BCX with a low intake of vitamin C. | Fair |
| Sugiura, 2012, Japan [27] | No | Prospective cohort (4 years) | 187 (age 60.5 ± 5.8) | Postmenopausal female | Tertile of serum BCX concentration Q1 (0.24–1.41 μM) Q2 (1.43–2.39 μM) Q3 (2.41–10.53 μM) |
Odds ratios for osteoporosis and osteopenia | Yes | The higher serum concentration of BCX was significantly related to the reduced risk of osteopenia and osteoporosis. | Good |
| Imagama, 2011, Japan [28] | No | Cross-sectional | 286 (age 50–85) | Male, female | Serum cryptoxanthin concentration (mean ± SD) Case, 0.25 ± 0.16 μM; control, 0.35 ± 0.33 μM |
Existence of lumbar osteophyte | Not reported | The serum level of cryptoxanthin was significantly higher in ‘no osteophytes’ group. | Fair |
| Sahni. 2009 (1), United States [29] | No | Prospective cohort (4 years) | 874 (age 75 ± 5) | Male, pre-/postmenopausal female | Tertile of BCX intake | Femur BMD; spine BMD; radius BMD | Yes | The intake of BCX was not related to the changes in any type of BMD. | Fair |
| Sugiura, 2008, Japan [30] | No | Cross-sectional | 699 (age 30–70) | Male, pre-/postmenopausal female | Quartile of serum BCX concentration Q1 (0.22–1.07 mM) Q2–4 (1.10–10.53 mM) |
Correlation analysis; odds ratios for low level of BMD | Yes | Positive correlations between serum BCX and BMD were observed in the postmenopausal female. | Fair |
| Yang, 2008, United States [31] | No | Case-control | Case, 30 (age 63.3 ± 10.8); control, 29 (age 62.1 ± 6.2) | Postmenopausal female | Serum BCX concentration (mean ± SD) Case, 0.27 ± 0.18 μM; control, 0.43 ± 0.36 μM Dietary BCX intake (mean ± SD) Case, 0.16 ± 0.19 mg/day; control, 0.09 ± 0.15 mg/day |
Incidence of osteoporosis | Yes | The average serum concentration of BCX was significantly high in the control group compared to the osteoporosis group. Dietary BCX showed an opposite aspect as the overall intake of BCX was higher in the osteoporosis group. | Fair |
| Maggio, 2006, Italy [32] | No | Case-control | Case, 45 (age 70.3 ± 6.4); control, 45 (age 70.1 ± 5.9) | Postmenopausal female | Plasma BCX concentration Case, μM; 0.230 (0.129–0.397); control, 0.580 (0.363–0.715) μM |
Incidence of osteoporosis | Not reported | The plasma concentration of BCX was significantly higher in control compared to the osteoporotic group. | Fair |
†: Evaluated by following either Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies or Quality Assessment of Case-Control Studies guideline of National Institutes of Health (NIH). BMD, bone mineral density; BMI, body mass index, BCX, β-cryptoxanthin.