Osteoporosis and sarcopenia share common risk factors and there is considerable overlap in their pathophysiology. Sedentary lifestyle, insufficient caloric, protein and micronutrients intake, decrease vitamin D assumption and production, tabagism, potus, chronic inflammation and glucocorticoid assumption compromise both tissues. Furthermore, muscle and bone derive from mesenchymal stem cells, therefore same genetic polymorphisms can influence their trophism. Finally, their mechanical and biochemical interactions explain why alterations in one tissue can compromise the health status of the other. Indeed, a positive correlation between lean body mass and bone mineral density has been demonstrated. Bone and muscle are dynamic and need mechanical loads to avoid atrophy and preserve strength. In particular, the muscle mechanical forces on periosteum stretch collagen fibres and stimulate bone formation. Thus, sarcopenia or just a reduction in physical activity can alter the delicate balance between bone formation and reabsorption. The biochemical crosstalk between muscle and bone occurs though systemic (i.e. hormones: growth hormone/insulin-like growth factor-1, sex hormones and vitamin D) and local factors (i.e. myokines and osteokines). Trophic hormones decline with ageing, thus favouring the onset of both osteoporosis and sarcopenia. Among the local factors, myostatin is one of the most studied. It is a myokine member of the transforming growth factor beta superfamily which decreases myoblast proliferation, and exerts its effects also on bone and tendon. However, it remain unclear whether myostatin levels increase with ageing and if its activity linearly correlates with its quantity. Aging is also characterized by a reduction in bone marrow mesenchymal stromal cells and in their production of vascular endothelial growth factor (VEGF) which promotes myoblast proliferation. Lastly, the effect of lipotoxicity, consequent to the adipose replacement of atrophied muscle and bone, should be considered. Adipose cells produce inflammatory citokines which exert negative effects both on muscle and on bone cells. A small cross sectional substudy of the SarcoPhage study, an ongoing project evaluating sarcopenia among community dwelling older people, proved that the prevalence of sarcopenia was higher among people with osteoporosis and osteopenia. The inverse relation was also demonstrated: the number of osteoporotic or osteopenic participants was higher among people with muscle impairment. These results were confirmed in a wider sample of Finnish postmenopausal women in which sarcopenia and its components (low muscle mass, strength and performance) were associated to higher risk of osteoporosis. However, it is quite difficult to estimate the prevalence of osteo-sarcopenia since it depends on the clinical setting. A subanalysis of the data from the Study of Osteoporotic Fractures and from the Osteoporotic Fractures in Men Study estimated the prevalence of osteosarcopenia of 11.8% in women and 2% in men. A higher prevalence was instead observed in Chinese community dwelling older people (15.1% in women and 10.4% in men) and in the Women’s Health and Aging Study II (about 16% in women). The number of osteoporotic patients is even greater (37%) when considering specific subsettings like older people with a history of falling. Intuitively, an impairment in two systems (i.e. muscle and bone) compromises physiological reserves at a higher degree than deficit in each one does. Therefore, people suffering from both impairments are more vulnerable to stress and more frail. Indeed a cross-sectional observational study of patients referred to a Falls & Fractures Clinic in Australia showed that people with osteosarcopenia had a higher risk of falling and fracturing than robust people without osteoporosis or people suffering from either single condition. Anyway, the greater risk of fracture in osteosarcopenic patients was confirmed only in men from a subanalysis of the Osteoporotic Fractures in Men Study but not in women from a subanalysis of the Study of Osteoporotic Fractures. Different results come from a longitudinal study in older Australian men. In this study sarcopenia was the component of osteosarcopenia associated with a greater risk of falls and osteopenia the component associated with a greater risk of fractures. Therefore, osteosarcopenic participants did not have a higher risk of falls and fractures than men with either condition alone. These findings were confirmed in another prospective Australian study which considered separately low muscle mass (sarcopenia) and low muscle strength (dynapenia). Both patients with a combination of low muscle and bone mass (ostesarcopenic) and those with low muscle strength and low muscle mass (osteodynapenic) did not have a significantly greater risk of fracture or mortality compared to people with sarcopenia alone, dynapenia alone or osteopenia alone. Do we need to operationalise osteosarcopenia as a standing alone condition to reinforce the association between osteoporosis and sarcopenia? Considering the evidence so far probably not. Osteoporosis and sarcopenia are two pathologies which can occur concomitantly in complex, old individuals but osteosarcopenia should not be considered a new disease from a pathophysiologic point of view. As geriatricians we should reject the “stand alone disease approach” and promote a holistical approach to the elderly.

Osteosarcopenia nel grande anziano / S. Damanti, M. Cesari. ((Intervento presentato al convegno L'interazione endocrino-metabolica tra osso e muscolo scheletrico: rilevanza clinica nei diversi quadri di malattia e opportunità d'intervento tenutosi a Milano nel 2019.

Osteosarcopenia nel grande anziano

S. Damanti
Primo
;
M. Cesari
Ultimo
2019

Abstract

Osteoporosis and sarcopenia share common risk factors and there is considerable overlap in their pathophysiology. Sedentary lifestyle, insufficient caloric, protein and micronutrients intake, decrease vitamin D assumption and production, tabagism, potus, chronic inflammation and glucocorticoid assumption compromise both tissues. Furthermore, muscle and bone derive from mesenchymal stem cells, therefore same genetic polymorphisms can influence their trophism. Finally, their mechanical and biochemical interactions explain why alterations in one tissue can compromise the health status of the other. Indeed, a positive correlation between lean body mass and bone mineral density has been demonstrated. Bone and muscle are dynamic and need mechanical loads to avoid atrophy and preserve strength. In particular, the muscle mechanical forces on periosteum stretch collagen fibres and stimulate bone formation. Thus, sarcopenia or just a reduction in physical activity can alter the delicate balance between bone formation and reabsorption. The biochemical crosstalk between muscle and bone occurs though systemic (i.e. hormones: growth hormone/insulin-like growth factor-1, sex hormones and vitamin D) and local factors (i.e. myokines and osteokines). Trophic hormones decline with ageing, thus favouring the onset of both osteoporosis and sarcopenia. Among the local factors, myostatin is one of the most studied. It is a myokine member of the transforming growth factor beta superfamily which decreases myoblast proliferation, and exerts its effects also on bone and tendon. However, it remain unclear whether myostatin levels increase with ageing and if its activity linearly correlates with its quantity. Aging is also characterized by a reduction in bone marrow mesenchymal stromal cells and in their production of vascular endothelial growth factor (VEGF) which promotes myoblast proliferation. Lastly, the effect of lipotoxicity, consequent to the adipose replacement of atrophied muscle and bone, should be considered. Adipose cells produce inflammatory citokines which exert negative effects both on muscle and on bone cells. A small cross sectional substudy of the SarcoPhage study, an ongoing project evaluating sarcopenia among community dwelling older people, proved that the prevalence of sarcopenia was higher among people with osteoporosis and osteopenia. The inverse relation was also demonstrated: the number of osteoporotic or osteopenic participants was higher among people with muscle impairment. These results were confirmed in a wider sample of Finnish postmenopausal women in which sarcopenia and its components (low muscle mass, strength and performance) were associated to higher risk of osteoporosis. However, it is quite difficult to estimate the prevalence of osteo-sarcopenia since it depends on the clinical setting. A subanalysis of the data from the Study of Osteoporotic Fractures and from the Osteoporotic Fractures in Men Study estimated the prevalence of osteosarcopenia of 11.8% in women and 2% in men. A higher prevalence was instead observed in Chinese community dwelling older people (15.1% in women and 10.4% in men) and in the Women’s Health and Aging Study II (about 16% in women). The number of osteoporotic patients is even greater (37%) when considering specific subsettings like older people with a history of falling. Intuitively, an impairment in two systems (i.e. muscle and bone) compromises physiological reserves at a higher degree than deficit in each one does. Therefore, people suffering from both impairments are more vulnerable to stress and more frail. Indeed a cross-sectional observational study of patients referred to a Falls & Fractures Clinic in Australia showed that people with osteosarcopenia had a higher risk of falling and fracturing than robust people without osteoporosis or people suffering from either single condition. Anyway, the greater risk of fracture in osteosarcopenic patients was confirmed only in men from a subanalysis of the Osteoporotic Fractures in Men Study but not in women from a subanalysis of the Study of Osteoporotic Fractures. Different results come from a longitudinal study in older Australian men. In this study sarcopenia was the component of osteosarcopenia associated with a greater risk of falls and osteopenia the component associated with a greater risk of fractures. Therefore, osteosarcopenic participants did not have a higher risk of falls and fractures than men with either condition alone. These findings were confirmed in another prospective Australian study which considered separately low muscle mass (sarcopenia) and low muscle strength (dynapenia). Both patients with a combination of low muscle and bone mass (ostesarcopenic) and those with low muscle strength and low muscle mass (osteodynapenic) did not have a significantly greater risk of fracture or mortality compared to people with sarcopenia alone, dynapenia alone or osteopenia alone. Do we need to operationalise osteosarcopenia as a standing alone condition to reinforce the association between osteoporosis and sarcopenia? Considering the evidence so far probably not. Osteoporosis and sarcopenia are two pathologies which can occur concomitantly in complex, old individuals but osteosarcopenia should not be considered a new disease from a pathophysiologic point of view. As geriatricians we should reject the “stand alone disease approach” and promote a holistical approach to the elderly.
11-mag-2019
Settore MED/09 - Medicina Interna
Osteosarcopenia nel grande anziano / S. Damanti, M. Cesari. ((Intervento presentato al convegno L'interazione endocrino-metabolica tra osso e muscolo scheletrico: rilevanza clinica nei diversi quadri di malattia e opportunità d'intervento tenutosi a Milano nel 2019.
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