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1. Introduction

Anorexia nervosa, an eating disorder characterized by restrictive eating and an intense fear of gaining weight, is a complex condition which includes psychiatric anomalies, secondary amenorrhoea, nutritional damage, impaired endocrine panel up to bone loss as well as cardiac, gastrointestinal, and hematological complications (1,2). Every organ actually may be affected by the disease; thus, there is a need for a multidisciplinary team in addition to multiple hospitalization episodes (1,2). Not only long term requirements but also a high mortality rate is described in relation to malnutrition and weight loss (2,3).

Eating disorders such as anorexia nervosa have exhibited an alarming increasing incidence due to social pressure especially through social media (3-5). This increasing incidence has been reported for the last few decades but especially during the last 6 months of 2020 when it has become a challenging issue due to the pandemic period (6,7) Lockdown recommendations refocused the population on viral content which aggressively imposed unrealistic models of weight and body image (6,7). The two major features of the condition may be characterized as a life threatening situation with side effects affecting each body system with an alarming increasing incidence (1,4).

2. Aim of the review

This is a review which includes an update on the eating disorder anorexia nervosa from three perspectives: The gynecological endocrine panel of anomalies, damage to bone status, and the pressure of recent global pandemic transformations on subjects who display the condition.

3. Research method

This is a narrative review. The most explored database was Pub Med. A number of 54 references are quoted. We found 12 reports strictly related to anorexia nervosa and COVID-19 infection.

4. Panel of endocrine changes in anorexia nervosa

Psychiatric components of anorexia nervosa involving body image anomalies, damaging behaviors in order to promote weight loss (more than 15% reduction of the ideal body weight or a body mass index less than 17.5 kg/m2) are associated with secondary amenorrhea which underlines central hypogonadism (8,9).

In addition to this, other endocrine anomalies including hypothyroxinemia, hypercorticism, low insulin-like growth factor-1 (IGF1-1) production and hypoleptinemia have been reported (8,9). The lost of fat tissue due to a hypercatabolic status acts as an endocrine disruptor, also impairing communication with the hypothalamus-pituitary-thyroid, respective adrenal, and ovarian axes (8-10). This connection is translated in clinical practice; for instance at least 20.5% body fat mass is needed in order to achieve menstruation in young adult females (11). These pathways are supplementary destroyed by stress (for example, the new worldwide pandemic), which represents an epigenetic factor in anorexia nervosa (8).

Neuroendocrine pathways are also disrupted in this disease since there is miscommunication between brain-gut-adipose tissue, and anomalies of peptides underlying satiety and appetite regulation may act as disruptors of these pathways (12,13). Anorexia nervosa is a life threatening situation while endocrine, nutritional and electrolytic deterioration expose the patient to additional risks, including infections or cardiovascular diseases (14-16).

To date, there is a paucity of literature data regarding the specific risk of COVID-19 infection to anorexic patients. This complex psychiatric disease is very well studied but the exact link between metabolic and neuroendocrine changes are not completely understood up to the present (17).

5. Bone status

Fat tissue loss and dysfunction due to massive weight loss causes bone deterioration in addition to nutritional disturbances and endocrine/metabolic complications (18,19). Extreme phenotypes of anorexia nervosa are characterized by liver dysfunction, anemia, thrombocytopenia, leucopenia, bradycardia, hypoglycemia, and low vitamin D and calcium levels (18,19). Deficiency in estrogen levels decreases bone mineral density (as seen in menopausal status or in young females with other causes of hypogonadism such as premature ovarian failure) (20,21). However, estrogen replacement therapy does not entirely restore bone mineral density values because of the fact that other mechanisms in addition to estrogens are also involved in the skeleton status. Thus include: Chronic inflammation [for example, higher levels of pro-inflammatory cytokine tumor necrosis factor (TNF) have been reported], high cortisol values, anomalies of leptin (such as low circulating levels or high soluble leptin receptor levels) and of adiponectin, impaired bone-gut-fat communication and abnormal variations of bone turnover markers (22,23). Constant exposure to high oxidative status and dysregulation of the gut microbiota represent other contributors to skeleton status damage (24,25).

Moreover, most cases of anorexia have an onset during puberty thus the acquisition of peak bone mass is impaired as well as linear growth (26,27). Weight correction may be accompanied by catch up growth (but not always) while reaching the maximum potential of peak bone mass (which is 20-40% influenced by lifestyle intervention) is less likely to be entirely recovered (28,29). A total of 90% of women with anorexia nervosa have low bone mineral density more than 1 standard deviation below the values for age-matched healthy women (28,30).

Premenopausal osteoporosis represents a common co-morbidity in this particular type of eating disorder (31,32). The pharmacological intervention consists in the resumption of menses by estrogen use (33,34). The use of biphosphonates is controversial due to the fact that there is a limited number of available studies as well as the potential harmful effect of these drugs on future pregnancy (35,36). Some cases treated with teriparatide have been reported for severe cases of osteoporosis (31).

Thus, since the anti-osteoporotic approach with medicine is not consistent, the importance of lifestyle intervention is reflected in weight gain and providing adequate levels of vitamin D and calcium (37,38). Low sun exposure (which may be seen during lockdown restrictions) or the use of facial masks may impair adequate vitamin D intake during the pandemic period.

6. COVID-19 and anorexia nervosa

A recent 2020 study of the early COVID-19 effects on individuals with eating disorders based on self-reports reported associated increased anxiety and alarming eating behaviors during the pandemic (6). More than 1,000 participants from the US and The Netherlands answered online questions related to COVID-19(6). A total of 62%, respective 69% of the individuals had anorexia nervosa and they experienced worries about their dietary schedules while subjects with bulimia nervosa or binge eating disorders reported more episodes of binging when compare to the pre-pandemic period (6). The use of tele-medicine may bring some kind of improvement to these issues based on this survey (6).

Another UK survey which also used online data found a negative impact of the pandemic on subjects with eating disorders (39). The study was conducted on 129 subjects aged between 16 and 65 years (39). The following issues need to be taken into consideration: New living conditions, social distancing, self-isolation, changes in food access, more intense use of social media platforms, disruption of daily habits, and more difficult access to healthcare practitioners (39). Early pandemic data showed that coronavirus disease restrictions (not the disease itself) impaired the access to eating disorder services while changes of routine activities brought supplementary stress to the subjects (40).

A controlled study from China, based on the observations of eating disorder caregivers, showed a higher rate of depression and anxiety on 254 patients vs. a control group of 254 healthy subjects (41). Among persons with anorexia nervosa, the subgroup at higher risk included subjects with a longer period of time since diagnosis, and those with close relatives who did not live with them (41).

Longitudinal data were collected before and during lockdown on 74 patients with anorexia nervosa or bulimia vs. 97 healthy control subjects using questionnaires (42). While bulimic individuals exacerbated binge eating behaviors, anorexic patients were associated with an increased compensatory physical exercise, and patients with both conditions had more frequent episodes of relapse during the pandemic outbreak if the condition was previously remitted (42). Early data from the COLLATE (COVID-19 and you: Mental health in Australia now survey) project studied 5,469 participants from the Australian population with eating disorders and found excessive purging and binging behaviors (43).

The transition to telehealth was brought by global changes due to infection with the novel coronavirus and many medical domains switched their daily clinical program to online practice (44,45). The level of interest from the general population was found to depend on pathology, geographic area or the moment of lockdown (45,46). This adjustment was also conducted for providing health care to patients with eating disorders (44). Some utility of the novel system has been confirmed (44). Nutritional recommendations through telehealth are also used for subjects without anorexia nervosa (47). Since physiological support in eating diseases also includes sessions with the entire family, family-based therapy using videoconferencing was also recommended during the pandemic period, but we should mention that this online method of gathering the entire family has been previously suggested (48,49).

Another observation, although with a relatively low level of evidence, is the potential association of eating disorders with a higher risk of suicide (50,51). Moreover, low weight and impaired immunity may represent negative factors for COVID-19 infection itself (52).

A study on 159 subjects with anorexia nervosa showed a 37% decrease in access to in-person physiological/psychotherapy control and a 46% reduction in general practitioner check-ups while videoconferencing was used by 26% of patients, and 35% of them had a telephone consultation (53). COVID Isolation Eating Scale (CIES) was launched in September 2020 representing a collaborative international study aiming to explore the pandemic impact on subjects with eating disorders and obesity (54). Among the different subgroups, anorexic patients had the highest level of dissatisfaction to remote therapy vs. prior face-to-face treatment (55).

Overall, the current pandemic day's prescription is marked by access through digital medicine. The access to investigations might be reduced but drug administration should not be postponed, if considered necessary. When it comes to therapy options referring to low bone mineral density/osteoporosis in patients of reproductive age suffering anorexia nervosa, we mention first vitamin D supplements and adequate calcium intake if necessary (in addition to menses control) (55-57). Typical drugs used for menopausal osteoporosis such as antiresoptives (bisphosphonates, denosumab) and bone-forming agents such as teriparatide are not encouraged in premenopausal women unless severe conditions such as prevalent osteoporotic fractures are exhibited since the potential harmful effect of future pregnancy is still a matter of discussion (56-58).

7. Conclusions

Anorexia nervosa, a severe condition affecting every organ of the body including bone status, needs to be taken into consideration during the COVID-19 pandemic period because of a higher risk of relapse associated with the new living conditions, social distancing, self-isolation, changes in food access, more intense use of social media platforms, disruption of daily habits, and more difficult access to healthcare practitioners. The lack of physical activity in addition to vitamin D deficiency related to low sun exposure or to the use of facial masks should also be considered when it comes to further bone damage.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

All information included in the Review is documented by relevant references.

Authors' contributions

MCD critically revised the manuscript for its content. FS revised the manuscript and is the corresponding author. MC summarized the literature findings and wrote the manuscript. RCP revised the literature data. AAGG and AP researched the articles that were included as references. AV reviewed the literature findings and critically revised the manuscript and approved the current form of the article in order to be submitted to the journal. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References