Response to “A comment on ‘Osteosarcopenia: A Geriatric Giant of the XXI Century”

Abstract

In the second half of the XX century, Bernard Isaacs coined the term «geriatric giants»: immobility, instability, incontinence, and impaired intellect/memory (1). He considered them as «giants» because of «their high statistical frequency in older persons and the huge personal burden of sufferers, escalating the need for socio-medical interventions.» Since then, lots of research has been dedicated to understanding and treat those giants, especially dementia (impaired intellect/memory), where the development of a biomarker or an effective treatment has remained elusive. Nevertheless, geriatricians have adopted these giants as the main targets in their clinical practice. However, other diseases that are equally highly prevalent in older persons affecting their functional independence, and reducing their quality of life (QoL) and survival have not received the same recognition and priority in geriatrics practice. This is the case of osteoporosis and sarcopenia, which are not being widely integrated in medical training programs and clinical practice despite being characterized in the second half of the XX century. Even with a large amount of evidence, clear diagnostic criteria, and high effectiveness of current treatments, osteoporosis remains underdiagnosed and undertreated (2). On the other hand, sarcopenia was introduced in 1988 (3), and a new ICD-10-CM (M62.84) code in September 2016 represented a significant step forward in recognizing sarcopenia as a disease (4). However, and despite its clinical significance, as with osteoporosis, integrating sarcopenia in clinical practice remains challenging (5). In 2009, in their pivotal editorial, Binkley and Buehring proposed the term «sarco-osteopenia» to describe a subset of frailer older individuals with both osteopenia/osteoporosis and sarcopenia, and that could be at a higher risk of falls, fractures, frailty and mortality (6). Since then, the term has evolved into «osteosarcopenia» and is generating growing interest from multiple angles and by several research groups worldwide (7). Together, skeletal muscle and bones constitute 55% of a healthy person’s body mass, provide postural stability and facilitate movement. Interestingly, new knowledge has demonstrated that the muscle/bone interaction is significantly more complex than portrayed by traditional siloed approaches that have focused on and studied these organs separately while limiting their interaction to primarily mechanical. We now understand that, in addition to their anatomical connections, muscles and bones communicate via hormonal and biochemical messengers (8). Importantly, these biochemical interactions and endocrine roles affect other organs and systems; thus, alterations in bone and muscle mass and function have clinical consequences that go far beyond the musculoskeletal system (9). Some questioners of the term osteosarcopenia have referred to the multiple cross-talks between organs and systems that could be equally affected by disease. Indeed, although «cardiosarcopenia» could be observed in heart failure, or «thyrosteoporosis» could occur in hyper or hypothyroidism, there are multiple reasons to propose osteosarcopenia as a separate entity, consequence of shared pathophysiology, with common clinical outcomes and potential combined therapeutic targets. Importantly, no two tissues in the body show a similar decline in their structure and function under aging and pathological conditions as bone and muscle do. For instance, immobility (one of the geriatric giants) is rapidly associated with a decline in both tissues, thus predisposing to adverse outcomes (i.e. falls, disability), which prevents an effective response to rehabilitation (10). Regarding its pathophysiology, osteosarcopenia is the consequence of multi-directional abnormalities in the bone muscle cross-talk and local changes that have been fully summarized elsewhere (11), and that could be closely associated with the geroscience model (12), in which several age-related diseases share similar pathophysiological mechanisms. Interestingly, fat has become a third player in the pathophysiology of osteosarcopenia (13), not necessarily because of the presence of obesity, but because of the increasing levels of fat infiltration that are observed inside the bone marrow in osteoporotic bone and the dramatic levels of intramuscular fat infiltration observed in sarcopenic muscle (13). These high levels of fat infiltration, which are independent of the subject body mass index, are known to be lipotoxic, affecting the function and structure of the local tissues (14). Whether high levels of fat infiltration could be used as a diagnostic or therapeutic tool for osteosarcopenia remains unknown but offers a novel and exciting approach that deserves further exploration. A major source of confusion in the field comes from a specific clinical phenotype and adverse outcomes associated with osteosarcopenia (15). Being a geriatric syndrome (giant) and not a specific disease, osteosarcopenia is considered as the combined presence of osteopenia/osteoporosis and sarcopenia in the same patient, which is expected to predispose them to adverse outcomes such as falls, fractures, frailty, disability, © Serdi and Springer-Verlag International SAS, part of Springer Nature