Osteosarcopenic obesity: potential clinical implications
The financial burden of each representative component of osteosarcopenic obesity is substantial. For instance, in 2008, direct costs of obesity were estimated to total almost 14 billion US dollars [52], with even more capital lost in indirect costs such as absenteeism, disability, and premature mortality [53]. Direct medical expenditure related to sarcopenia was estimated in 2000 to be around 18.5 billion dollars per year [54]. Those with osteoporosis with a concurrent hip fracture may contribute more than 6 billion dollars on health-care costs per year in order to treat the fracture and underlying osteoporosis; those with osteoporosis without a fracture may contribute to 3.79 billion dollars of health-care costs [55], though both of these estimates are conservative compared to an alternative 13.7–20.3 billion-dollar estimate [5]. Cleary, these three conditions substantially augment the direct cost of the US health-care expenditure with extensive presumed indirect costs. A disease state such as osteosarcopenic obesity would therefore prove to be a considerable economic encumbrance.
Obesity alone and its related consequences is perhaps one of the most comprehensively studied and debated modern epidemics. The prevalence of obesity across a multitude of countries has accelerated in the last decade [56]. In the USA, 32.2 % of men and 35.5 % of women are classified as obese according the WHO cut points [57]. Though the mechanisms of obesity are yet to be elucidated, excess adiposity has been shown to be related to heart disease, type II diabetes, osteoarthritis, sleep apnea, reproductive abnormalities, certain cancers, high blood pressure, dyslipidemia, stroke, and liver/gallbladder disease [58]. In a clinical setting, obese patients may be more susceptible to infections, notably nosocomial, periodontal, postsurgical, and respiratory infections [59]. Moreover, those who are obese may experience greater mobility-related functional impediments [60] as well as walking limitations [61], which is particularly important in osteosarcopenic obesity.
Sarcopenia has its own assortment of detrimental clinical outcomes. Disability assessed by questions concerning activities of daily living can aggravate the development of sarcopenia, especially in those with severe sarcopenia (defined as a ASM index  < 8.50 kg/m2 in men and <5.75 kg/m2 in women); due to its bidirectional nature, sarcopenia may lead to disability, and disability may further initiate sarcopenia [18, 62], thus creating an infinite cycle. Elderly individuals who lose fat-free mass (FFM) are over two times more likely to report disability compared to those who do not lose FFM [63]. Additionally, sarcopenia is also associated with increased mortality in the oldest (80+ years of age) frail elderly [64]. Smaller muscle mass and greater fat infiltration in muscle has been shown to have a negative relationship to lower extremity performance repeatedly measured by walking and standing/sitting assessments [65].
On its own, osteopenia/osteoporosis is a known risk factor for fractures. Fractures in particular have numerous adverse clinical implications, including an increased risk of mortality. In fact, those who experience a hip fracture have a mortality rate that is three times higher than the general population, in part due to complications faced after the fracture [66]. Men have a lower life expectancy after hip fracture than women [67], though only 25–30 % of hip fractures occur in men [68]. Those who are victims of a fracture face adverse consequences such as compromised ability to perform activities of daily living [69], increased risk of subsequent fractures, and negatively altered quality of life [70]. The fracture can negatively affect an elderly individual’s ability to walk independently and complete daily activities; more alarmingly, these patients may have an increased risk of premature entrance into nursing facilities [71].
In addition to each component’s individual implications, combined disorders can influence the development of even more adverse outcomes, and one disorder may cause another. For example, in addition to the separate side effects of sarcopenia and obesity, sarcopenic obese patients have a higher incidence of impaired function [72], diminished quality of life [43], knee osteoarthritis [73], falls, disability [29], and chemotherapy toxicity [1, 74] and shorter survival in cancer patients [75] in comparison to individuals with normal body composition; this is most likely due to the dual affliction of both low muscle mass and excess adiposity. Though obesity may have a protective role on osteoporosis [76], some research has suggested that a high body weight may actually perpetuate the development of osteoporosis [77]. A large examination of over 60,000 women reported that high body weight is not protective against fracture incidence, but may in fact be associated with ankle and upper leg fractures [78]. Furthermore, those with the most muscle wasting and lowest grip strength have much higher odds of having osteoporosis, fractures, or falls than those who have more muscle mass and strength [79]. Clearly, these conditions are interrelated, and the occurrence of one may aid in the development of another and thus lead to compounded clinical implications.
Importantly, osteosarcopenic obesity is not a syndrome of elderly individuals. There are a variety of disease states and conditions where the disease itself or its treatment is associated with losses of skeletal muscle and bone alongside gains in adipose tissue. For instance, low BMD in adulthood can be caused by type 1 diabetes mellitus (DM), though the association between type II DM and osteoporosis is less clear [80]. Diabetes treated with insulin therapy can lead to weight gain [81], and insulin resistance can lead to accelerated muscle loss mainly due to metabolic and hormonal factors [82]. Therefore, those with diabetes are likely to present with osteosarcopenic obesity. Sarcopenia has been found to occur independently of BMI in patients diagnosed with respiratory and gastrointestinal cancers and can precipitate the loss of functional status [75]. Patients undergoing cancer therapies (especially victims of breast cancer) may be at risk for bone loss, as some treatments may suppress estrogen production (which has a protective effect on bone) as well as directly adversely affect bone metabolism [83]. Yet another clinical manifestation, chronic obstructive pulmonary disease (COPD), is associated with muscle wasting and weakness which can make even daily tasks difficult, leading to decreased activity that further intensifies sarcopenia development [84]. COPD patients display numerous risk factors for osteoporosis including smoking, physical inactivity, vitamin D deficiency, low body weight, and hypogonadism. Of particular concern is glucocorticoid use which may directly adversely affect BMD, leading to secondary osteoporosis [85]. In HIV patients, antiretroviral interventions are associated with weight gain [86] along with bone loss through multiple mechanisms; the disease itself is associated with a loss in lean mass [87], suggesting that these patients commonly suffer from osteosarcopenic obesity.
Clearly, the direct impact of osteosarcopenic obesity is a potential threat to clinical and public health. Considering the effects of low muscle and bone tissues combined with the influence of obesity, it is likely that these individuals will present with poorer clinical outcomes caused by the cascade of metabolic abnormalities associated with these changes in body composition. Regardless of the specific diagnosis cut points for muscle, bone, and adipose tissue that have yet to be determined, there is no doubt that future research is needed to explore the clinical outcomes and appropriate interventions associated with the concurrent appearance of all three conditions.