Table 2.
Summary of the Relationship Between MetS and Bone Health
| Study | Study Design | Subjects Characteristics | Definition of MetS | Summary of Bone Health Assessment |
|---|---|---|---|---|
| Xue et al (2012)8 | Meta-analysis of 9 studies (1 outlier study excluded) | 11 studies included for review (10 for LS, 7 for FN BMD), involving 13,122 subjects, 2779 were MetS. | NCEP-ATPIII | MetS was associated with increased spine BMD [weighted mean difference (WMD) 0.03; 95% CI 0.01~0.04] not femoral BMD (WMD 0.01; 95% CI −0.01~0.03) |
| Zhou et al (2013)9 | Meta-analysis of 9 studies published before 2013 | Studies that compared BMD between subjects with or without MetS | NCEP-ATPIII | Subjects without MS had higher BMD at: Femoral neck: WMD 0.02 (95% CI 0.01~0.03) Lumbar spine: WMD 0.01 (95% CI 0.00~0.03) Sub-analysis: covariate-adjusted lumbar spine BMD significantly higher in men only (WMD 0.02, 95% CI 0.01~0.03). |
| von Muhlen et al (2007)18 | Rancho Bernardo Study, a longitudinal cohort study with mean follow-up of 2 years. | Community-dwelling ambulatory men (417) and women (671), all Caucasian in southern California, aged 38 to 97 years. | NCEP-ATPIII | MetS reduced the femoral neck BMD of in men after BMI-adjustment (0.737; SEM 0.013 g/cm2 in MetS vs 0.769; SEM 0.007 g/cm2 in non-MetS). Positive predictors of BMD in women (age-adjusted): TG for total hip (β 0.104; p 0.004) and spine (β 0.107; p=0.006) WC for total hip (β 0.293; p <0.001), femoral neck (β 0.225; p<0.001) and spine (β 0.267; p<0.001) FBG for femoral neck (β 0.093; p=0.01) Positive predictors of BMD in men (age-adjusted): HDL for total hip (β 0.093; p=0.01) WC for total hip (β 0.368; p<0.001), femoral neck (β 0.287; p <0.001) and spine (β 0.347; p<0.001) FBG for spine (β −0.136; p=0.006) |
| Kinjo et al (2007)17 | NHANES III: A cross-sectional study | 8197 Americans > 20 years. Mean age for MetS = 56.7±16.7 years; non-MetS = 44.2±8.7 years. | NCEP-ATPIII | Femoral neck BMD increased in subjects with MetS (0.86; 95% CI 0.85~0.86 g/cm2) compared to subjects without MetS (0.80; 95% CI 0.80~0.80 g/cm2) (p<0.001). BMI-adjustment attenuated the difference (p>0.05). Abdominal obesity increased femoral neck BMD (0.86; 95% CI 0.85~0.86 g/cm2 vs 0.78; 95% CI 0.78~0.79 g/cm2 for those without abdominal obesity) |
| Park et al (2010)14 | Cross-sectional study | 399 post-menopausal Korean women (mean age 59.4, SD=6.7 years) who went to a medical hospital for check-up | NCEP-ATPIII | Femoral neck BMD was higher in women with MetS (0.82; SD 0.12 g/cm2) compared to those without MetS (0.85; SD 0.09 g/cm2) in age-adjusted model (p=0.011). Further adjustment with BMI attenuated the difference (p>0.05). |
| Kim et al (2010)155 | Cross-sectional study | 1780 men > 40 years (55.7 ± 8.1 years) and 1108 post-menopausal women (57.1 ± 6.7 years) attending a health promotion centre. | IDF and AHA/NHLBI | Men with MetS had lower BMD adjusted for all covariates: AHA/NHLBI criteria: MetS 0.813, SD 0.008 g/cm2; non-MetS 0.839, SD 0.004 g/cm2; p=0.002 IDF criteria: MetS 0.766, SD 0.012 g/cm2; non-MetS 0.839, SD 0.003 g/cm2; p<0.001 Postmenopausal women with MetS had lower BMD adjusted for all covariates: AHA/NHLBI criteria: MetS 0.684, SD 0.008 g/cm2; non-MetS 0.721, SD 0.004 g/cm2; p<0.001 IDF criteria: MetS 0.675, SD 0.011 g/cm2; non-MetS 0.719, SD 0.004 g/cm2; p<0.001 MetS components associated with BMD: Men: WC (β −0.250, p<0.001) Women: WC (β −0.138, p<0.001), TG (β −0.097, p=0.001) |
| Hwang and Choi (2010)25 | Cross-sectional study | 2548 women aged 18 years attending a health promotion centre | NCEP-ATPIII | Women without MetS (0.898, SEM 0.007 g/cm2) had higher vertebral BMD compared to those with (0.914, SEM 0.003 g/cm2) (p=0.031). Women without abdominal obesity (0.922, SEM 0.004 g/cm2) had higher vertebral BMD compared to those without (0.894, SEM 0.005 g/cm2) (p<0.001). Women without hypertriglyceridemia (0.916, SEM 0.003 g/cm2) had higher vertebral BMD compared to those without (0.895, SEM 0.006 g/cm2) (p=0.002). |
| Hernández et al (2010)12 | Camargo Cohort Study: A cross-sectional Study (2006–2009) | 1508 subjects (495 men and 1013 women) > 50 years, > 90% Caucasians from Cantabria, Spain | NCEP-ATPIII | In women, age-adjusted BMD values were higher in those with MetS: Lumbar spine - MetS: 0.942, SEM 0.008 g/cm2; non-MetS: 0.909, SEM 0.005 g/cm2; p=0.001 Femoral neck - MetS: 0.755, SEM 0.007 g/cm2; non-MetS: 0.709, SEM 0.004 g/cm2; p<0.001 Total hip - MetS: 0.886, SEM 0.007 g/cm2; non-MetS: 0.831, SEM 0.004 g/cm2; p=0.001 BMI adjustment attenuated differences at all site (p>0.05) In women, components of MetS associated with BMD were: Lumbar spine – WC (mean difference 0.110, p= 0.005) and HPT (mean difference 0.204, p< 0.001) Femoral neck - WC (mean difference 0.123, p= 0.001) and HPT (mean difference 0.277, p<0.001) Total hip - WC (mean difference 0.133, p<0.001) and HPT (mean difference 0.354, p<0.001) |
| Hernández et al (2011)44 | Camargo Cohort Study: A cross-sectional study$ | 1209 adults (421 men aged 65±9 (50–92 years) and 788 women 63±9 (44–88 years)) visiting a primary care centre | JIS | Women with MetS had higher quantitative ultrasound indices adjusted for age compared to women without: SOS: 1545(2.2) vs 1538(1.5), p=0.01 BUA: 68(1.3) vs 63(0.8), p=0.006 QUI: 91(1.4) vs 85(0.9), p=0.008 Further adjustment for BMI attenuated the difference (p>0.05) In women, WC was associated with all quantitative ultrasound indices SOS: β 0.127, p=0.002 BUA: β 0.164, p< 0.0001 QUI: β 0.354, p< 0.0001 MetS did not influence quantitative ultrasound indices in men. |
| Bullo et al (2011)42 | The NUTERA-PREDIMED Cohort study: A large, parallel-group, randomized, controlled study$ | 251 subjects with 124 men and 127 women, aged between 55–80 years (men) or 60–80 years (women) from Spain | NCEP-ATPIII | Subjects with MetS (74.35, SEM 1.83) had higher BUA than those without (79.04, SEM 1.36) (p=0.045). Other quantitative ultrasound indices were similar between the two groups (p>0.05). Subjects with type II diabetes mellitus (79.41, SEM 1.43) had higher BUA than those without (74.73, SEM 1.62) (p=0.032). Other quantitative ultrasound indices were similar between the two groups (p>0.05). All comparison adjusted to sex only. |
| Cvijetic et al (2011)43 | Cross-sectional study$ | 211 men and women, mean age 77.9±4.5 years, randomly selected from voter registry. | IDF | Men with MetS (94.0, SD 23.7) had lower QUI compared to men without (108.5, SD 13.9) (p=0.007), even after BMI-adjustment. Women with MetS (81.7, SD 23.7) had higher QUI compared to women without (69.5, SD 13.9) (p=0.01). After BMI adjustment, the difference was not significant. Diabetes was associated with QUI (β=0.44, p=0.005) in men. Obesity (β=0.45, p=0.035) and WC (β=0.57, p=0.027) was associated with QUI in women. |
| Jeon et al (2011)27 | Cross-sectional study | 2265 women (1234 premenopausal and 931 postmenopausal) > 45 years visiting the Health Promotion Center | NHLBI | Premenopausal women Women without MetS had higher BMD compared to those with MetS after adjusting for all covariates. Lumbar spine: 1.154, SEM 0.004 vs 1.110, SEM 0.017 (MetS); p=0.014 Femoral neck: 0.903, SEM 0.003 vs 0.885, SEM 0.013 (MetS); p=0.177 Predictor of lumbar spine BMD: SBP (β −0.122, p<0.001) Predictor of femoral neck BMD: DBP (β −0.112, p<0.001) and WC (β 0.079, p=0.007) Post-menopausal women Women without MetS had higher BMD compared to those with MetS after adjusting for all covariates. Lumbar spine: 0.147, SEM 0.005 vs 1.111, SEM 0.014 (MetS); p=0.017 Femoral neck: 0.896, SEM 0.004 vs 0.870, SEM 0.010 (MetS); p=0.016 Predictor of lumbar spine BMD: DBP (β −0.080, p=0.014) Predictor of femoral neck BMD: DBP (β −0.097, p=0.002) and CRP (β −0.064, p=0.001) |
| Kim et al (2013)34 | KNHANES: A cross-sectional study | 14,485 adults (6659 men and 7826 women) from South Korea. | NHLBI | Men with MetS had lower BMD compared to those without MetS after adjusting for all covariates including BMI. Total hip: 0.962, SEM 0.004 (MetS) vs 0.971, SEM 0.003; p=0.030 Femoral neck: 0.801, SEM 0.004 (MetS) vs 0.814, SEM; 0.003 p<0.001 MetS did not influence the BMD of women. Predictors of lumbar spine BMD: Linear regression - Men: TG (β −70.91, p<0.001) Premenopausal women: HDL-c (β −6.08, p=0.002) Postmenopausal women: None Logistic regression - Men: Obesity (OR 1.393, 95% CI 1.330~1.458), abdominal obesity (OR 1.339, 95% CI 1.271~1.410), diabetes mellitus (OR 1.103, 95% CI 1.017~1.196), high TG (OR 0.927, 95% CI 0.865~0.994) Premenopausal women: Obesity (OR 1.696, 95% CI 1.572~1.830), abdominal obesity (OR 1.606, 95% CI 1.504~1.714), LDL-c (OR 1.145, 95% CI 1.071~1.224) Postmenopausal women: Obesity (OR 1.512, 95% CI 1.394~1.640), abdominal obesity (OR 1.349, 95% CI 1.241~1.467), HPT (OR 1.133, 95% CI 1.029~1.246) Predictors of total hip BMD (components of MetS): Linear regression - Men: WC (β −2.41, p=0.007), insulin (β −4.58, p<0.001), HOMA-IR (β −1.11, p<0.001), TG (β −78.88, p<0.001) Premenopausal women: insulin (β −1.74, p=0.009), HOMA-IR (β −0.37, p=0.034) Postmenopausal women: None Logistic regression - Men: Obesity (OR 1.734, 95% CI 1.628~1.847), abdominal obesity (OR 1.471, 95% CI 1.378~1.569), high TG (OR 0.922, 95% CI 0.854~0.994) Premenopausal women: Obesity (OR 2.214, 95% CI 2.033~2.412), abdominal obesity (OR 1.971, 95% CI 1.833~2.119), LDL-c (OR 1.086, 95% CI 1.007~1.171), HDL-c (OR 1.230, 95% CI 1.033~1.465) Postmenopausal women: Obesity (OR 1.850, 95% CI 1.665~2.056), abdominal obesity (OR 1.651, 95% CI 1.487~1.833) Predictors of femoral neck BMD (components of MetS): Linear regression - Men: DBP (β −4.50, p=0.001), insulin (β −4.16, p<0.001), HOMA-IR (β −1.09, p<0.001), triglycerides (β −115.25, p<0.001) Premenopausal women: WC (β 2.13 p=0.007), HOMA-IR (β −0.33, p=0.036) Logistic regression – Men: Obesity (OR 1.559, 95% CI 1.467~1.657), abdominal obesity (OR 1.438, 95% CI 1.347~1.534), hypertension (OR 0.937, 95% CI 0.879~0.998) high triglyceride (OR 0.862, 95% CI 0.798~0.932) and MetS (OR 0.899, 95% CI 0.840~0.962) Premenopausal women: Obesity (OR 1.939, 95% CI 1.776~2.117), abdominal obesity (OR 1.802, 95% CI 1.677~1.936), high triglycerides (OR 1.244, 95% CI 1.040~1.488) Postmenopausal women: Obesity (OR 1.751, 95% CI 1.558~1.968), abdominal obesity (OR 1.606, 95% CI 1.426~1.809) |
| Kim et al (2013)31 | KNHANES: A cross-sectional study | 3207 South Koreans, mean age for men = 48.4 years, premenopausal women = 36.5 years and postmenopausal women = 64.8 years. | JIS | MetS was associated with low bone mass (osteopenia+osteoporosis) in multiple adjusted models: Overall subjects: OR 1.38, 95% CI 1.07~1.79 Men: OR 1.49, 95% CI 1.04~2.14 MetS was not associated with low bone mass Men with hyperglycemia had higher total hip BMD (mean difference compared to normal men 0.018, SEM 0.007, p<0.05) Men with high TG had lower femoral neck BMD (mean difference compared to normal men −0.018, SEM 0.007, p<0.01) Women with high TG had higher BMD at all site Lumbar spine: mean difference 0.021, SEM 0.010, p<0.05 Femoral neck: mean difference 0.016, SEM 0.007, p<0.05 Total hip: mean difference 0.019, SEM 0.008, p<0.05 |
| Kim et al (2013)11 | KNHANES cross-sectional study | 2989 South Koreans > 20 years. | NCEP-ATPIII | Men with MetS had higher BMD in fully adjusted models: NCEP <45 years Femoral neck 0.876, SD 0.004 (MetS) vs 0.843, SD 0.014, p<0.05 Spine 1.000, SD 0.004 (MetS) vs 0.979, SD 0.013, p=0.147 ≥45 years Femoral neck 0.773, SD 0.004 (MetS) vs 0.746, SD 0.008, p=0.01 Spine 0.955, SD 0.006 (MetS) vs 0.927, SD 0.011, p=0.05 IDF <45 years Femoral neck 0.877, SD 0.004 (MetS) vs 0.826, SD 0.016, p=0.01 Spine 1.001, SD 0.004 (MetS) vs 0.963, SD 0.016 p=0.05 ≥45 years Femoral neck 0.772, SD 0.004 (MetS) vs 0.745, SD 0.010, p=0.05 Spine 0.95, SD 0.005 (MetS) vs 0.919, SD 0.013, p=0.05 Similar differences in BMD were not observed in women. Predictors of femoral neck BMD: Men < 45 years: WC (β −0.007, p<0.001), SBP (β 0.001, p<0.05), DBP (β −0.002, p<0.01), TG (β −0.001, p<0.05) Men ≥ 45 years: WC (β −0.004, p=0.001), DBP (β −0.001, p=0.05) Premenopausal women: TG (β −0.001, p<0.05) Postmenopausal women: WC (β −0.002, p<0.05) Predictors of spine BMD: Men < 45 years: WC (β −0.005, p<0.001), SBP (β 0.001, p<0.01), DBP (β −0.002, p<0.01), TG (β −0.001 p<0.05) Men ≥ 45 years: WC (β −0.005, p<0.01), SBP (β 0.001, p<0.01), DBP (β −0.002 p<0.01) Premenopausal women: WC (β −0.001, p<0.05), SBP (β 0.001, p<0.05), DBP (β −0.001 p<0.05), HDL-c (β −0.001, p<0.05) Postmenopausal women: WC (β −0.002, p<0.05) |
| Kim et al (2013)20 | 3-year retrospective longitudinal study, follow-up period 3 years | 1218 post-menopausal women | NCEP-ATPIII | More decline in BMD in women with MetS (Bone site: Annualized BMD % change (95% CI) of MetS vs No MetS, p-value) Total femur: −1.118 (−1.195~−1.041) vs −0.895 (−1.045~−0.745), p=0.011 Femur neck: −1.078 (−1.157~−0.998) vs −0.904 (−1.059~−0.749), p=0.048 Trochanter: −1.503 (−1.629~−1.377) vs −1.128 (−1.373~−0.882), p=0.009 Lumbar spine: −0.877 (−0.990~−0.765) vs −0.619 (−0.838~−0.399), p=0.043 Predictors of % change of BMD: Total femur: WC β 0.105, p=0.025; TG β 0.076, p=0.006 Trochanter: WC β 0.135, p=0.005; TG β 0.085, p=0.003 |
| El Maghraoui et al (2014)53 | Cross-sectional study | 270 post-menopausal women with mean age 61.0 years ± 7.8 (range 50 to 90) from Rabat area, Morocco. | NCEP-ATPIII | Metabolic syndrome was associated with osteoporosis (OR 0.291, 95% CI 0.130~0.651) |
| Muka et al (2015)46 | The Rotterdam Study: A cross-sectional study with prospective follow up (mean follow-up 6.7 years) for fracture risk | 2040 women (mean age 72.38 ±6.81 years) and 1510 men (72.04 ± 6.51 years) from Dutch | JIS | MetS was associated with: Bone width: Women (β −0.054, 95% CI −0.091~-0.018), men (β −0.029 95% CI −0.068~0.010) Buckling ratio: Women (β −0.81, 95% CI −1.34~-0.27), NS for men. Longitudinal bone loss was associated with MetS in women (β 0.028, 95% CI 0.012~0.043) in fully adjusted model, NS for men. Predictors for femoral neck BMD: Women: hyperglycemia (β=0.016, p=0.01), HDL-c (β=0.013, p=0.01) Men: hyperglycemia (β=0.022, p=0.004), WC (β=−0.030, p=0.004) |
| Eckstein et al (2016)10 | Berlin Aging Study II: A cross-sectional study | 1402 subjects (51.1% women) aged 68 ± 4 years | JIS | In women, MetS was associated positively with BMD in the fully adjusted model: Spine: β 0.369 p=0.005 Hip: β 0.202 p=0.028 NS for femoral BMD In men, MetS was not associated with BMD of any site in the fully adjusted model. In men with MetS, BMD was associated with trunk fat: Hip: β –0.039, p=0.004 Femur: β –0.042, p=0.002 In men with or without MetS, BMD was associated with WC: Spine - No MetS: β –0.089, p=0.024; MetS: β –0.099, p=0.043 Hip - No MetS: β –0.075, p=0.001; MetS: β –0.054, p=0.043 Femur - No MetS: β –0.079, p=0.001; MetS: β –0.091, p=0.001 |
| Lin et al (2018)29 | Cross-sectional study | 2007 subjects (1045 men) aged ≤ 50 years (average 58.9 years) who went to a preventive examination agency in urban Taiwan | Definition of Bureau of Health Promotion, Taiwan | MetS was not significant associated with BMD in men: BMI< 24 kg/m2: 0.579, 95% CI 0.213~1.575 BMI≥ 24 kg/m2: 0.986, 95% CI 0.390~2.496 MetS was not significant associated with BMD in men: BMI< 24 kg/m2: 0.579, 95% CI 0.213~1.575 BMI≥ 24 kg/m2: 0.986, 95% CI 0.390~2.496 None of the MetS components was associated with BMD in both men and women. |
| Loke et al (2018)28 | Retrospective cross-sectional study | 1162 subjects (59.5% men) from a hospital in southern Taiwan with mean age 59.9 ± 7.3 years | NCEP-ATPIII | MetS was associated with decreased BMD in age-adjusted model (osteoporosis+osteopenia): Men: OR 0.35, 95% CI 0.18~0.68 Women: OR 2.24, 95% CI 1.06~4.69 In men, decreased BMD was associated with: Central obesity: OR 1.06, 95% CI 1.03~1.10 Hyperglycemia: OR 0.99, 95% CI 0.99~1.00 In women, no significant relationship between decreased BMD and MetS components. |
| Chen et al (2018)24 | Cross-sectional study | 938 post-menopausal women from Eastern China | Diabetes Society of Chinese Medical Association | MetS (OR 2.132, 95% CI 1.166~3.900) NAFLD (OR 1.945, 95% CI 1.162~3.253) or both conditions together (OR 5.632, 95% CI 3.281~9.666) predicted higher risk of osteoporosis. |
| Wani et al (2019)19 | Cross-sectional study | 1587 subjects (84.7% women), aged > 35 years from hospitals around Riyadh city, Saudi Arabia. | NCEP-ATPIII | Men: 3rd tertile T-score predicted high risk of MetS (OR 2.12, 95% CI 1.1~4.6) 3rd tertile T-score predicted high risk of central obesity (OR 3.07, 95% CI 1.2~7.5) Women: 2nd tertile T-score (OR 1.46, 95% CI 1.1~2.0) and 3rd tertile (OR 1.47, 95% CI 1.1~2.0) T-score predicted high risk of MetS. 2nd tertile T-score (OR 1.83, 95% CI 1.3~2.6) and 3rd tertile (OR 1.97, 95% CI 1.4~2.8) T-score predicted high risk of MetS. |
| Kim and Kim (2019)23 | KNHANES cross-sectional study (2008–2011) | 3058 Korean post-menopausal women ≥ 50 years. The subjects were classified as having WC obesity (≥80 cm), BMI obesity (>25 kg/m2) or both. | NCEP-ATPIII | Compared to non-obese subjects, the risk of osteoporosis: Reduced in BMI-defined obesity: OR 0.42, 95% CI 0.18~0.99 Reduced in BMI or WC-defined obesity: OR 0.66, 95% CI 0.44~1.00 |
| Chin et al (2020)16 | Cross-sectional study | 400 Malaysians aged ≥ 40 years (52.5% women) in Klang Valley | Joint interim statement | Before BMI-adjustment Lumbar spine: β 0.128, 95% CI 0.022~0.035 Femoral hip: β 0.165, 95% CI: 0.081~0.249 Osteoporosis risk: OR 0.545, 95% CI 0.221–1.346 After BMI-adjustment Lumbar spine: β 0.009, 95% CI −0.097~0.115 Femoral hip: β 0.006, 95% CI −0.079~0.091 Osteoporosis risk: OR 0.907, 95% CI 0.186~4.411 |
Notes: All the studies performed the BMD measurement via dual-energy X-ray absorptiometry, except for42–44 (labeled with$), which used quantitative ultrasonometry.
Abbreviations: β, standard regression coefficient; AHA/NHLBI, American Heart Association/National Heart, Lung, and Blood Institute; BMD, bone mineral density; BMI, body mass index; BUA, broadband ultrasound attenuation; CI, confidence interval; DBP, diastolic blood pressure; FBG, fasting blood glucose; HDL-c, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment of insulin resistance; HPT, hypertension; IDF, International Diabetes Federation; LDL-c, low-density lipoprotein cholesterol; MetS, metabolic syndrome; NAFLD, non-alcoholic fatty liver disease; NCEP-ATP–III, National Cholesterol Education Program Adult Treatment Panel III; NS, not significant; OR, odds ratio; QUI, quantitative ultrasound index; SBP, systolic blood pressure; SD, standard deviation; SEM, standard error of mean; SOS, speed of sound; TG, triglyceride; WC, waist circumference; WMD, weighted mean difference.