Full Length ArticleRelationship of cardiometabolic risk biomarkers with DXA and pQCT bone health outcomes in young girls
Introduction
Excess adiposity has been linked to the development of insulin resistance, chronic inflammation, and the ensuing metabolic syndrome (MetS) components (i.e. glucose intolerance, dyslipidemia, and hypertension) [1]. These metabolic alterations are known risk factors for cardiovascular disease [1], type 2 diabetes [2], non-alcoholic fatty liver disease [3] and certain cancers [4]. Recent evidence in animal [5,6] and human studies [[6], [7], [8], [9], [10]] has suggested that these obesity-derived metabolic alterations may also be risk factors for compromised bone strength. For example, von Muhlen et al. reported that fracture incidence was 2.6 times more likely to occur in older adults with MetS compared to older adults without MetS [8]. Moreover, the number of MetS components was negatively associated with femoral neck and total hip areal bone mineral density (aBMD) after adjustment for BMI [8]. Kim et al., also observed significantly lower femoral neck aBMD in participants with MetS after adjusting for body weight; however, when assessing associations of the individual MetS components with femoral neck BMD, waist circumference in both men and women and fasting triglycerides in women were the only MetS components having significant inverse relationships with aBMD [10]. Hence, not all components of MetS have similar associations with skeletal outcomes.
Despite evidence in adults of an association between cardiometabolic risk (CMR) factors and compromised bone health, less research has been focused around the effect of obesity-induced metabolic dysfunction on bone development in children. Recently, in a cohort of 9-to-12 year-old girls participating in the Soft Tissue and Bone Development (STAR) study, we have shown that the positive relationship between total body adiposity and whole body bone mineral content (BMC) was attenuated by the presence of 2 or more CMRs defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition of MetS modified for age [11]. In that analysis, the relationship of individual CMRs representative of inflammation, insulin resistance, dyslipidemia, and hypertension with bone outcomes independent of each other was not assessed. It is possible that the relationship of dyslipidemia with bone may be explained by insulin resistance, which underlies many of the MetS components [12]. Currently, few studies have evaluated single CMR biomarkers with bone in children, with inconsistent results [[13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]]. In addition, most previous studies in children have focused on the relationship of CMRs with dual-energy x-ray absorptiometry (DXA) measured total body BMC and aBMD. However, BMC and BMD are just two among several indicators of bone health. Bone strength is also comprised of other bone properties such as the microarchitecture at the bone tissue level [24]. With newer 3-dimentional imaging techniques, such as peripheral quantitative computed tomography (pQCT), both the material properties (i.e. density and mass) and the geometric properties (i.e. size and shape) of bone can be measured [25]. Obesity-related CMRs may have differential relationships with these different components of bone strength. For instance, Viljakainen et al. found that C-reactive protein (CRP), a biomarker of inflammation, was not significantly associated with whole body aBMD, but did have a significant inverse relationship with cortical density, periosteal circumference, and overall bone strength at the tibia in young male adults [26]. No study to our knowledge has assessed the associations of obesity-related CMR biomarkers of inflammation, insulin resistance, dyslipidemia, and hypertension together with measures of bone geometry and strength in children. Given the paucity of research assessing the effects of CMR biomarkers with bone indices in children, which is an important age for bone development, and an estimated prevalence of up to 7% of overweight children and 30% of obese adolescents having MetS [27], the aim of this study was to assess the combined and independent relationships of CMR biomarkers with total body and regional bone parameters in young girls.
Section snippets
Study population
The study participants consisted of 344 girls aged 9-to-12 years-old who participated in the cross-sectional arm of the Soft Tissue And Bone Development in Young Girls (“STAR”) study, a study designed to assess the effects of adiposity and related metabolic risk factors on bone development in girls (Clinical trials #NCT02654262). Detailed descriptions of the study protocol with inclusion and exclusion criteria have been published previously [11,[28], [29], [30]]. The study protocol was approved
Results
Descriptive characteristics of the sample are presented in Table 1. Based on U.S. age and gender-specific established cut-points for percentiles of body mass index (kg/m2) [44], the majority of girls had a healthy weight (59%). Only 2% of girls were underweight, while 15% were overweight, and 24% were obese. The majority of girls identified as Hispanic (74%). On average girls were 11 years-old and had just reached their estimated peak height velocity (maturity offset = 0.3 year). Self-reported
Discussion
The aim of this study was to assess the combined and independent relationships of CMR biomarkers with total body bone mass and density and regional bone parameters of geometry and strength in young girls. Our results showed that greater metabolic dysfunction as indicated by a higher CMR z-score was associated with decreases in total body BMC and BA. These findings are similar to those of Pollock et al., who observed that overweight adolescents with a clustering of 2 or more cardio-metabolic
Conclusion
In conclusion, greater cardio-metabolic dysfunction is associated with impaired total body bone strength and regional bone strength, especially that of trabecular bone in young girls. In particular, inflammation and insulin resistance are likely the CMR biomarkers underlying the negative associations observed between obesity-related cardio-metabolic dysfunction and negative bone health outcomes. Whether biomarkers of inflammation and insulin resistance can be used for not only assessing CVD
Declaration of interest
None.
Funding
This work was supported by the National Institute of Child Health and Human Development. [HD074565].
Acknowledgements
This study was executed at the University of Arizona Collaboratory for Metabolic Disease Prevention and Treatment Center. The study was supported by National Institute of Child Health and Human Development.
References (58)
- et al.
Overview of epidemiology and contribution of obesity to cardiovascular disease
Prog. Cardiovasc. Dis.
(2014) - et al.
Risk factors for the development of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, including genetics
Clin. Liver Dis.
(2018) - et al.
Adolescent obesity, bone mass, and cardiometabolic risk factors
J. Pediatr.
(2011) - et al.
Body fat mass, lean body mass and associated biomarkers as determinants of bone mineral density in children 6–8 years of age – the physical activity and nutrition in children (PANIC) study
Bone
(2018) - et al.
Metabolic syndrome reduces bone mineral density in overweight adolescents
Bone
(2014) - et al.
Relative contributions of lean and fat mass to bone strength in young Hispanic and non-Hispanic girls
Bone
(2018) - et al.
Validation of peripheral quantitative computed tomography-derived thigh adipose tissue subcompartments in young girls using a 3 T MRI scanner
J. Clin. Densitom.
(2018) - et al.
Metabolic syndrome risk assessment in children: use of a single score
Rev. Paul. Pediatr.
(2015) - et al.
iDXA, prodigy, and DPXL dual-energy X-ray absorptiometry whole-body scans: a cross-calibration study
J. Clin. Densitom.
(2009) - et al.
Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls
Bone
(2010)
Validation of a youth/adolescent food frequency questionnaire
Prev. Med.
Osteoporosis is associated with metabolic syndrome induced by high-carbohydrate high-fat diet in a rat model
Biomed. Pharmacother.
Bone mechanical properties and changes with osteoporosis
Injury
Interpretation of whole body dual energy X-ray absorptiometry measures in children: comparison with peripheral quantitative computed tomography
Bone
Metabolic syndrome as a risk factor for diabetes
Expert. Rev. Cardiovasc. Ther.
Obesity biomarkers, metabolism and risk of cancer: an epidemiological perspective
Recent Results Cancer Res.
Effects of metabolic syndrome on bone mineral density, histomorphometry and remodelling markers in male rats
PLoS One
The relationship between metabolic syndrome and osteoporosis: a review
Nutrients
Obesity, type 2 diabetes and bone in adults
Calcif. Tissue Int.
Associations between the metabolic syndrome and bone health in older men and women: the rancho Bernardo study
Osteoporos. Int.
The relationship between low bone mass and metabolic syndrome in Korean women
Osteoporos. Int.
Negative association between metabolic syndrome and bone mineral density in Koreans, especially in men
Calcif. Tissue Int.
Effect of cardiometabolic risk factors on the relationship between adiposity and bone mass in girls
Int. J. Obes.
Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European male ageing study
Osteoporos. Int.
Impaired glucose tolerance and bone mineral content in overweight latino children with a family history of type 2 diabetes
Diabetes Care
Lower bone mass in prepubertal overweight children with prediabetes
J. Bone Miner. Res.
Insulin resistance negatively influences the muscle-dependent IGF-1-bone mass relationship in premenarcheal girls
J. Clin. Endocrinol. Metab.
Insulin resistance and the IGF-I-cortical bone relationship in children ages 9 to 13 years
J. Bone Miner. Res.
Sex-specific relationships between insulin resistance and bone mineral content in Korean adolescents
J. Bone Miner. Metab.
Cited by (9)
Muscle-to-Bone and Soft Tissue-to-Bone Ratio in Children and Adolescents with Obesity
2023, Journal of Clinical DensitometryBone Health in Childhood Chronic Disease
2020, Endocrinology and Metabolism Clinics of North AmericaCitation Excerpt :Regular weight-bearing physical activity should also be emphasized, noting that children with T1D tend to be less active than peers.50 Emerging data in children suggest that cardiometabolic abnormalities associated with type 2 diabetes (T2D) may adversely influence skeletal development.51 There is growing interest in the use of noninsulin pharmacotherapy to treat childhood T2D.
Visceral adipose tissue and cardiometabolic risk factors in young Hispanic and non-Hispanic girls
2022, Frontiers in PediatricsRelationship between bone mineral density and biochemical parameters in obese children and adolescents
2022, Gazzetta Medica Italiana Archivio per le Scienze Mediche
- 1
Present address: University of Lisbon, Faculty of Human Kinetics, Exercise and Health Laboratory, CIPER, Estrada da Costa, 1499-002, Cruz Quebrada, Lisbon, Portugal.