Sarcopenia has been associated with numerous risk factors, the most prominent of these factors being old age and alterations in both hormonal and inflammatory parameters, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (commonly known as ESR)[34-36]. Rheumatoid arthritis (RA) is a disease that causes chronic inflammation and reduction in physical activity[37,38]. Skeletal muscle index has been shown to be lower in patients with RA compared to healthy controls[39]. Furthermore, a recent study revealed an association between sarcopenia and diseases that cause chronic inflammation. Therefore, a close relationship between RA and sarcopenia may exist.

In one study[39], RA patients with sarcopenia were found to have higher CRP values than those without, even though there was no difference between these patients in terms of DAS28 (disease activity score for RA). A similar systematic review comparing RA and sarcopenia etiology found that lower bone mineral density was more common among RA patients with sarcopenia[40]. These findings show that RA patients may be predisposed to sarcopenia regardless of RA severity. In addition, various studies have reported that the pain-related reduction in physical activity among RA patients can result in the development and progress of sarcopenia[38,41,42]. For instance, a study authored by Munro et al[43] found that CRP and ESR levels were negatively correlated with muscle mass in a cohort of 97 RA patients. Furthermore, muscle loss in RA, “rheumatoid cachexia” defined as loss of muscle mass in the absence of fat tissue reduction, has been shown to occur in many patients with RA[44]. The effects of cachexia overlap with sarcopenia pathophysiology, and most patients with cachexia are sarcopenic[45]. Considering that muscle loss is the hallmark of sarcopenia, rheumatoid cachexia could explain the higher frequency of sarcopenia among RA patients.

Furthermore, inflammatory parameters, including those that are altered in RA (tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), cytokines that tend to increase with age [interleukin 1 (IL-1) and interleukin-6 (IL-6)], have been associated with the development of sarcopenia[42,43]. However, the definition of sarcopenia was directly associated with muscle mass in both of these studies. Schaap et al[36] defined it as at least a 3% loss of muscle mass, while Ngeuleu et al[37] defined it as a reduction in relative skeletal mass index (< 5.5 kg/m² for women and < 7.26 kg/m² for men). In addition to population-based studies, it is known that cytokines, especially TNF-α and IL-6, stimulate protein catabolism in the muscle, leading to muscle loss. Thus, diseases with chronic inflammatory characteristics are thought to cause secondary sarcopenia, which exemplifies another association between RA and sarcopenia[46,47].

Although many of the aforementioned studies have reported significant associations between RA and sarcopenia in terms of etiology and laboratory/clinical findings, there are also studies that did not find any relationship[48]. The majority of studies that suggest a very close association between the two diseases have only revealed associations between specific etiological factors and some clinical findings. Therefore, although it is tempting to conclude that RA and sarcopenia have a causal relationship (one way or the other), the literature is actually insufficient to draw such a conclusion. Further controlled studies, with the goal of determining which condition causes or leads to the other (preferably prospective studies or comparison of patients with early/long term disease), are required to confirm whether a causal relationship exists between the two diseases.

Osteoarthritis (OA) is associated with aging, chronic inflammation and obesity. Considering that aging and chronic inflammation are also factors for sarcopenia development and progress, a significant association between these two conditions may exist. Various studies have shown an association between the type of cytokines that increase during both conditions[49,50], while one study reported that OA and sarcopenia may potentiate each other’s inflammatory activities through the production of pro-inflammatory agents[51]. Another important point is the fact that patients with OA have lowered physical activity, which may lead to muscle loss and sarcopenia[52,53].

A study by Kemmler et al[54] found that sarcopenia was more common in women with OA than those without. However, interestingly, muscle mass results were similar in both OA patients and those without arthritis. On the other hand, Toda et al[55] reported that reduced lower limb mass was frequent in patients with OA. This may suggest that the joints affected by OA are an important factor for the development of sarcopenia. Lower physical activity, especially in those with painful knee and hip joints, may translate to the exacerbation of muscle loss throughout the body, and could show a causal relationship between OA and sarcopenia[56]. This conclusion is supported by reports of lower skeletal muscle mass in patients with knee and hip OA[57,58]. However, it is important to keep in mind that the inflammatory condition brought about by sarcopenia could also both increase inflammatory burden in joints and increase OA severity. Current data are not sufficient to determine which condition causes or accelerates the other.

Therefore, it is apparent that current research has been unfruitful in determining whether sarcopenia is the cause or result of muscle problems in inflammatory diseases. Nevertheless, it is safe to say that a relationship between inflammatory stress and sarcopenia exists; however, further studies are required to determine the weight and direction of this relationship. Future studies that evaluate whether sarcopenia frequency is affected in those with inflammatory disease without joint pain (or the opposite) could potentially elucidate the nature of these associations.

Ankylosing spondylitis (AS) is a chronic inflammatory condition known to cause bone loss; however, muscle loss is not widely reported[59-61]. To our knowledge, only two studies suggest that muscle mass is reduced in those with AS. The first study[62] reported that patients with AS had significant reduction in lean body mass, while the second study evaluated muscle mass directly, and showed that both muscle mass and functional capacity were significantly reduced in patients with AS. The remaining studies showed no associations between AS and muscle mass[60,63]. While differences in measurement techniques and study design may cause variations in results, it is also crucial to keep in mind that AS primarily affects the vertebrae. Meanwhile, other joints are affected to a lesser degree, if at all. Thus, limitations in the movement of vertebrae may not be enough to accelerate or cause sarcopenia, even with increased inflammation.

One report[59] claims that patients with spondyloarthropathy had significantly lower muscle mass compared to controls. However, their findings showed a lack of association between changes in muscle mass and disease duration. This is an unexpected result, because if there was a strong relationship between the diseases, the findings of sarcopenia (muscle loss) should have worsened proportionately with disease duration. Therefore, we can conclude that the very limited literature on this topic does not confirm a positive relationship between spondyloarthropathy and sarcopenia.

In a study comparing sarcopenia frequency among patients with chronic inflammatory diseases and non-inflammatory controls, patients with systemic lupus erythematosus were found to have significantly higher sarcopenia frequency than controls[4]. However, the definition of sarcopenia was accepted as unintentional loss of > 10 pounds of weight in the previous year, while weakness was defined separately. This definition is lacking in terms of determining whether the patient truly had sarcopenia; however, considering that systemic lupus erythematosus patients may require high doses of corticosteroid therapy, the loss of muscle mass is to be expected. Future studies would benefit from correctly defining and evaluating sarcopenia with regard to steroid dose.

Muscle involvement is a very common finding in patients with systemic sclerosis (SSc), which may contribute to the development of sarcopenia. Although the literature is methodologically limited, many studies report that SSc patients have increased muscle loss, and sarcopenia is diagnosed in up to 20%–54% of these patients[64,65]. In a relatively larger study comprised of 61 SSc patients, it was reported that lean mass was significantly reduced in women with SSc. Furthermore, the same study showed that longer duration with SSc was associated with higher risk for sarcopenia[66]. The latter finding was also confirmed by Wang et al[67].

Psoriatic arthritis is another disease with chronic activation of inflammation, which primarily affects the skin in the form of lesions of varying severity. Fatigue is a common but underestimated feature of psoriasis; however, there was no association between psoriasis severity and fatigue severity, which may suggest that other factors lead to fatigue, such as sarcopenia development due to chronic inflammation[68]. A study by Krajewska-Włodarczyk et al[69] suggested that the quality of life of psoriasis patients was affected by fatigue, an underestimated and often overlooked clinical finding in psoriasis. Although the study did not directly evaluate sarcopenia, future studies may benefit from the evaluation of sarcopenia among patients with psoriatic arthritis, especially considering the association between inflammation and fatigue.

Although the majority of studies have not associated gout with sarcopenia, one large cross-sectional study found that the risk of sarcopenia was higher among gout patients[70]. In contrast, several studies have suggested that therapy for gout (allopurinol) could be protective against sarcopenia[71]. Allopurinol inhibits the enzyme xanthine oxidase, and has been shown to prevent the production of free radicals during muscle contraction[71]. Further studies are required to determine whether allopurinol can be used as a treatment in patients with sarcopenia.

Studies in this field have mostly focused on muscle mass in sarcopenic individuals. Although this approach is not entirely erroneous, it is important to remember that muscle mass evaluations may not capture the whole clinical picture in patients with sarcopenia, as these patients mainly suffer from reduced physical performance and muscle strength. Therefore, correctly defining sarcopenia in future studies will be of utmost importance in order to obtain accurate results. Furthermore, it is quite apparent that increased inflammation contributes to sarcopenia development. Therefore, sarcopenia research may benefit from better study designs that aim to discriminate between muscle strength and mass, while also taking into account the effect of inflammation on the condition. However, the available literature indicates significant associations between these inflammatory diseases and sarcopenia, a disease that causes significant morbidity and mortality. This finding, even by itself, can be considered as an important step in a field that has received insufficient attention.