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Schweighofer, N. DXA-Derived Indices in the Characterisation of Sarcopenia. Encyclopedia. Available online: https://encyclopedia.pub/entry/17953 (accessed on 05 December 2025).
Schweighofer N. DXA-Derived Indices in the Characterisation of Sarcopenia. Encyclopedia. Available at: https://encyclopedia.pub/entry/17953. Accessed December 05, 2025.
Schweighofer, Natascha. "DXA-Derived Indices in the Characterisation of Sarcopenia" Encyclopedia, https://encyclopedia.pub/entry/17953 (accessed December 05, 2025).
Schweighofer, N. (2022, January 10). DXA-Derived Indices in the Characterisation of Sarcopenia. In Encyclopedia. https://encyclopedia.pub/entry/17953
Schweighofer, Natascha. "DXA-Derived Indices in the Characterisation of Sarcopenia." Encyclopedia. Web. 10 January, 2022.
DXA-Derived Indices in the Characterisation of Sarcopenia
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This entry is adapted from the peer-reviewed paper 10.3390/nu14010186

Sarcopenia is linked with increased risk of falls, osteoporosis and mortality. No consensus exists about a gold standard “dual-energy X-ray absorptiometry (DXA) index for muscle mass determination” in sarcopenia diagnosis. Thus, many indices exist, but data on sarcopenia diagnosis agreement are scarce. Regarding sarcopenia diagnosis reliability, the impact of influencing factors on sarcopenia prevalence, diagnosis agreement and reliability are almost completely missing. 

DXA DXA-derived muscle mass indices BioPersMed cohort

1. Introduction

The increasing number of persons older than 60 years make sarcopenia an increasing problem for healthcare systems and societies since it increases physical frailty, disability [1] and hospitalisation risk[2], leading to long-term care placement[3] and increased mortality[4][5][6][7]. The prevalence of sarcopenia is amplified in the case of malnutrition, nutritional deficiencies and chronic diseases, such as cardiovascular disease, diabetes or liver cirrhosis, all of which are often seen in the elderly[8][9][10].
The definition of sarcopenia is based on two pillars: low muscle mass and low muscle function (strength or performance or both)[11]. During ageing, a loss of muscle mass of 8% per decade, starting at the age of 40 years, increases to 15% after 70 years of age. This occurs together with a decline in muscle strength, declining at a faster rate due to changed muscle quality[12][13]. Muscle mass can be determined by computed tomography, magnetic resonance imaging or spectroscopy, ultrasound and bioelectrical impedance analysis and dual-energy X-ray absorptiometry (DXA), the gold standard for body composition analysis[14][15]. DXA is also advised by the revised EWGSOP guidelines[4] for sarcopenia confirmation in practice.
Several DXA-derived muscle mass indices differing in the prediction of sarcopenia prevalence have been established. Only the impact of cut-off values on differences in sarcopenia prevalence is well known. Information regarding the impact of adjusting DXA-derived muscle mass indices, sarcopenia diagnosis agreement (often assuming that the same persons are diagnosed as sarcopenic), diagnosis reliability and possible influencing factors are lacking.
Since pharmacological approaches were not convincing, sarcopenia therapy is limited to a combination of exercise and protein supplementation[16][17]. To improve dietary muscle support, various macro- and micronutrients are under investigation. To determine the effects of new interventions and to allow an early start of intervention/therapy measures, a reliable determination of muscle mass changes and sarcopenia diagnosis in all sexes and weight groups is essential.

2. DXA-Derived Indices in the Characterisation of Sarcopenia

The main finding of this study was a large variation in the prevalence of sarcopenia dependent on the index and cut-off values used. A relatively high level of agreement of diagnosis of sarcopenia by only height-adjusted parameters, independent of the use of ALM or ASM as baseline parameters, exists. In comparison, a low level of agreement exists between sarcopenia diagnosis by unadjusted muscle mass parameters and indices adjusted by height only, weight only, and height and body fat. The type of adjustment defines which subjects are recognised as sarcopenic in terms of gender or BMI group. The investigated indices showed comparable reliability and stability of sarcopenia diagnosis in follow-up examinations.
Differences in prevalence of sarcopenia compared to previously published studies can be explained by the method of enrolment, since they are mostly cross-sectional population-based studies compared to our cohort study, including differences in ethnicity and the use of different cut-off points for sarcopenia diagnosis[18]. Errors in the estimation of muscle mass, namely that ASM represents 75% of total skeletal muscle mass and multiplication by 1.33 leads to total skeletal muscle mass, determine the low prevalence of sarcopenia defined by TSMI compared to AMMI[19][20]. The parameter of origin of the investigated indices had no influence on sarcopenia prevalence or diagnosis agreement.
The low level of agreement between differently adjusted indices is in line with the findings of Kemmler et al., but in their study of BIA was used to determine low muscle mass[21]. The low levels of sarcopenia diagnosis agreement between persons identified as sarcopenic in the case of ASM-based indices and ASM can be explained by the lack of adjustment of the latter, not taking into account any parameters determining the amount of muscle mass.
The type of adjustment itself contributes to the low level of agreement between indices. SMI (a weight-adjusted index) recognised mostly overweight persons as sarcopenic and might diagnose sarcopenia earlier than height-adjusted indices in these persons. This is strengthened by the fact that many persons with reduced handgrip strength are defined as sarcopenic only by SMI (kappa = 0.020; p < 0.001). In addition, SMI seems to diagnose sarcopenic obesity, a closely related but different disease. The investigated height-adjusted indices recognised sarcopenia mostly in normal-weight persons, clearly underestimating its prevalence in overweight/obese individuals. Due to more skeletal muscle mass but lower muscle quality following the incorporation of fat, in obese people[22], cut-off values for height-adjusted indices might be too low to detect sarcopenia in these individuals.
Our data indicate that neither height nor weight are ideal parameters for the adjustment of DXA- derived muscle mass parameters. No improvement of strength of agreement was gained by the adjustment of ALM with BMI (kappa: 0.003 with LESMI to 0.010 with SMI), since BMI, due to not including body fat percentage, race/ethnicity and the level of activity, does not reflect body composition well[22][23][24]. To address this problem, ALM adjusted to the waist to height ratio, body surface area or in% of weight[25] have been explored but were not satisfying enough to become commonly accepted. rLM is another improvement approach in which linear regression residuals of appendicular muscle mass adjusted for fat mass and height are used[26]. In our study, the level of agreement of rLM20 with SMI was low and only moderate with AMMI. New body composition indices might be better suited for adjustment but have not yet been tested in the diagnosis of sarcopenia. To overcome the flaws of the adjustment now recommended, the use of two adjustments in sarcopenia diagnosis, as investigated for bioelectrical impedance analysis, might be a solution[27].
When using DXA-derived indices to define sarcopenia, the use of cut-off values appropriate for the investigated cohorts in age and ethnicity is crucial. In the context of our cohort, this applies to rLMABC, SMI and LESMI[28][26]. For the last two indices, cut-off values for Caucasians are needed to make them completely comparable. The use of not only sex, but also age-adjusted cut off values, comparable to Z-values in the case of BMD, could be of value.
To determine the reliability of the diagnosis of sarcopenia by each index, we validated our baseline with follow-up results. We assumed that the absence of sarcopenia diagnosis in the follow-up visit indicated that the baseline finding was not reliable since no sarcopenia treatment was taken. Since these are persons at cardiovascular risk, an intervention to decrease it might have been taken, although neither type of dietary intervention nor exercise should impact sarcopenia. Some of the study participants might have changed their lifestyle due to retirement within the two years follow-up interval. The level of agreement between sarcopenia diagnosis in both visits of the indices was comparable. Thus, no index seems to be more reliable than the others.
We noted some gender-specific differences: Dependent on the index used, the prevalence of sarcopenia ranged from 0.9 to 50.3% in men and 0.6 to 36.3% in women. Height adjusted indices recognised more females, whereas for weight-adjusted SMI, more men were identified as sarcopenic. The reliability of sarcopenia was comparable for all indices, with the exception of SMI, which was significantly more reliable in men than in women.
The lack of vitamins D and K have been associated with sarcopenia prevalence[29][30][31]. Sarcopenia therapy currently combines dietary strategies such as protein supplements and, in the case of sarcopenic obesity, caloric restriction and exercise (most effectively resistance training). This combination is not completely satisfying, and positive effects of the addition of vitamin D or K have been proposed[31][32]. Vitamin K, via enabling of vitamin K dependent proteins to bind calcium by carboxylation, is a known regulator of extra- and intracellular calcium homeostasis. Together with parathyroid hormone, vitamin D and hypolactasia as regulators and modulators of systemic calcium levels, we investigated the dephosphorylated, uncarboxylated Matrix-GLA-protein as a surrogate parameter of vitamin K. Neither vitamin D deficiency nor hypolactasia associated with sarcopenia and parathyroid hormone significantly associated with sarcopenia, as defined by rLM20. Dephosphorylated, uncarboxylated Matrix-GLA-protein presented only at the lowest tertile (representing high vitamin K levels); significant associations with sarcopenia defined by AMMI, LESMI and rLM20, indicated a vitamin K independent pathway.

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