Lean mass and fat mass have differing associations with bone microarchitecture assessed by high resolution peripheral quantitative computed tomography in men and women from the Hertfordshire Cohort Study

Highlights

• Lean mass index is independently associated with cortical geometry.

• Fat mass index is related to trabecular microarchitecture after adjustment for lean mass index.

• Future studies should confirm direction of causality and explore mechanisms underlying tissue-specific associations.

Abstract

Understanding the effects of muscle and fat on bone is increasingly important in the optimisation of bone health. We explored relationships between bone microarchitecture and body composition in older men and women from the Hertfordshire Cohort Study. 175 men and 167 women aged 72–81 years were studied. High resolution peripheral quantitative computed tomography (HRpQCT) images (voxel size 82 μm) were acquired from the non-dominant distal radius and tibia with a Scanco XtremeCT scanner. Standard morphological analysis was performed for assessment of macrostructure, densitometry, cortical porosity and trabecular microarchitecture. Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Lean mass index (LMI) was calculated as lean mass divided by height squared and fat mass index (FMI) as fat mass divided by height squared. The mean (standard deviation) age in men and women was 76 (3) years. In univariate analyses, tibial cortical area (p < 0.01), cortical thickness (p < 0.05) and trabecular number (p < 0.01) were positively associated with LMI and FMI in both men and women. After mutual adjustment, relationships between cortical area and thickness were only maintained with LMI [tibial cortical area, β (95% confidence interval (CI)): men 6.99 (3.97,10.01), women 3.59 (1.81,5.38)] whereas trabecular number and density were associated with FMI. Interactions by sex were found, including for the relationships of LMI with cortical area and FMI with trabecular area in both the radius and tibia (p < 0.05). In conclusion, LMI and FMI appeared to show independent relationships with bone microarchitecture. Further studies are required to confirm the direction of causality and explore the mechanisms underlying these tissue-specific associations.

Introduction

Sarcopenia is defined as the loss of skeletal muscle mass and strength that occurs with advancing age [1]. As current demographic shifts are leading to an ageing population, the number at risk of sarcopenia is growing. Similarly, rates of obesity are also rising with dietary changes and more sedentary lifestyles. Previous work has suggested that both sarcopenia and obesity relate to bone mineral density (BMD) and hence fracture risk [2], [3], [4], [5]. Specifically, sarcopenia has been shown to be a risk factor for fracture through an increase in fall frequency [6], [7] and an association with poorer bone health [2], [3]. Obesity is associated with greater total body fat mass. Interestingly, some studies have found areal BMD to be positively associated with fat mass [4], [5] whereas others did not [8], [9].

The relationship between muscle and bone is driven by multiple mechanisms. These include the hormones, such as growth hormone, with positive effects on both tissues and the mechanostat whereby forces from muscle contractions act to stimulate bone. Dietary factors and physical activity are also thought to play a role. Associations between fat and bone occur mainly through the action of oestrogen, which augments bone health, and adipokines, which can have both positive and negative effects. Other hormones and cytokines have also been implicated. Furthermore, increased loading from greater adiposity may also influence bone through the mechanostat [10].

Many epidemiological studies have assessed body composition using dual energy X-ray absorptiometry (DXA) [4], [8]. DXA provides estimates of lean mass and fat mass but does have limitations. Although the majority of lean mass is made up of muscle, it also encompasses other tissues including tendon and ligament. Measurements can also be influenced by trunk thickness and level of tissue hydration, and ectopic fat is often significantly underestimated. Using other imaging modalities, fat can additionally be subdivided by its distribution. Studies have shown that subcutaneous adipose tissue (SAT) demonstrates different relationships with bone health than visceral adipose tissue (VAT) [11].

Relationships with bone structure have also been explored. Investigators have found consistent positive associations between lean mass and both bone geometry and estimates of bone strength [12], [13], [14]. Conversely, although some positive relationships have been shown between adiposity and bone geometry, the specific compartments affected have varied, and relationships with volumetric BMD, particularly cortical, have been inconsistent [12], [13], [15]. Furthermore, lean mass and fat mass are correlated; those with greater adiposity also tend to have larger muscles. Consequently, there is the potential for their relationships with bone health to confound one another. Previous work, including from the Framingham study, has highlighted the importance of adjusting lean mass for total fat mass both in the assessment of sarcopenia prevalence and when assessing associations with adverse outcomes [16], [17].

Although we are aware of some of the mechanisms through which muscle, fat and bone are interconnected, this area is not fully understood. Further analysis is required to unpick the individual associations of muscle with bone and fat with bone. These tissues are highly interdependent with mesenchymal stem cells having the capacity to differentiate into fat, bone or muscle. We know that fatty tissue may be deposited within the muscle, particularly with advancing age, and this may also occur within the bone [18]. It is very important to understand these relationships as this may shed light on which mechanisms are most likely to be driving each of the independent associations identified.

To date, the independent relationships of muscle and fat with bone microstructure, including trabecular microarchitecture and cortical porosity, have not been well described. These bone parameters can now be assessed non-invasively, in vivo using high-resolution peripheral quantitative computed tomography (HRpQCT). The purpose of the current study is to extend current knowledge by investigating the relationships of bone geometry, volumetric BMD, and bone microarchitecture with both lean mass and fat mass in a well phenotyped cohort of older men and women from Hertfordshire.