Owen J. Kelly

Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels.

While sarcopenia and sarcopenic obesity have been recognized in the last decade, a combined concept to include decreased muscle mass and strength, as well as decreased bone mass with coexistence of adiposity is discussed here. We introduce a new term, osteopenic obesity, and operationalize its meaning within the context of osteopenia and obesity. Next, we consolidate osteopenic obesity with the already existing and more familiar term, sarcopenic obesity, and delineate the resulting combined condition assigning it the term osteosarcopenic obesity. Identification and possible diagnosis of each condition are discussed, as well as the interactions of muscle, fat and bone tissues on cellular level, considering their endocrine features. Special emphasis is placed on the mesenchymal stem cell commitment into osteoblastogenic, adipogenic and myogenic lineages and causes of its deregulation. Based on the presented evidence and as expounded within the text, it is reasonable to say that under certain conditions, osteoporosis and sarcopenia could be the obesity of bone and muscle, respectively, with the term osteosarcopenic obesity as an encompassment for all.

Long-chain polyunsaturated fatty acids may mutually benefit both obesity and osteoporosis

The overconsumption of n-6 polyunsaturated fatty acids (PUFA), resulting in a high ratio of n-6 to n-3 PUFA, may contribute to the increased pathogenesis of obesity and osteoporosis by promoting low-grade chronic inflammation (LGCI). As evidence suggests, both obesity and osteoporosis are linked on a cellular and systemic basis. This review will analyze if a relationship exists between LGCI, fat, bone, and n-3 PUFA. During the life cycle, inflammation increases, fat mass accumulates, and bone mass declines, thus suggesting that a connection exists. This review will begin by examining how the current American diet and dietary guidelines may fall short of providing an anti-inflammatory dose of the n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It will then define LGCI and outline the evidence for a relationship between fat and bone. Inflammation as it pertains to obesity and osteoporosis and how EPA and DHA can alleviate the associated inflammation will be discussed, followed by some preliminary evidence to show how mesenchymal stem cell (MSC) lineage commitment may be altered by inflammation to favor adipogenesis. Our hypothesis is that n-3 PUFA positively influence obesity and osteoporosis by reducing LGCI, ultimately leading to a beneficial shift in MSC lineage commitment. This hypothesis essentially relates the need for more focused research in several areas such as determining age and lifestyle factors that promote the shift in MSC commitment and if current intakes of EPA and DHA are optimal for fat and bone.

Low-grade chronic inflammation perpetuated by modern diet as a promoter of obesity and osteoporosis

Abstract Some of the universal characteristics of pre-agricultural hominin diets are strikingly different from the modern human diet. Hominin dietary choices were limited to wild plant and wild animal foods, while the modern diet includes more than 70 % of energy consumed from refined sugars, refined vegetable oils, and highly processed cereals and dairy products. The modern diet, with higher intake of fat has also resulted in a higher ratio of omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acids (PUFA), contributing to low-grade chronic inflammation (LGCI) and thus promoting the development of many chronic diseases, including obesity and osteoporosis. In this review, we describe the changes in modern diet, focusing on the kind and amount of consumed fat; explain the shortcomings of the modern diet with regard to inflammatory processes; and delineate the reciprocity between adiposity and inflammatory processes, with inflammation being a common link between obesity and osteoporosis. We present the evidence that overconsumption of n-6 PUFA coupled with under-consumption of n-3 PUFA results in LGCI and, along with the increased presence of reactive oxygen species, leads to a shift in mesenchymal stem cells (precursors for both osteoblasts and adipocytes) lineage commitment toward increased adipogenesis and suppressed osteoblastogenesis. In turn, high n-6 to n-3 PUFA ratios in the modern diet, coupled with increased synthesis of pro-inflammatory cytokines due to adiposity, propagate obesity and osteoporosis by increasing or maintaining LGCI. Sažetak Pojedina univerzalna svojstva prehrane hominina prije pojave poljodjelstva izrazito se razlikuju od suvremene prehrane. Prehrambene navike hominina vjerojatno su bile ograničene na plodove divljeg bilja i lovinu; više od 70 % moderne prehrane odnosi se na konzumaciju rafiniranih šećera, biljnih ulja, žitarica i mliječnih prerađevina. Moderna je prehrana s višim unosom masti također dovela do nepovoljnijeg omjera omega-6 i omega-3 višestruko nezasićenih masnih kiselina (engl. krat. PUFA), koji pridonosi održavanju kronične upale niskoga stupnja, a time i nastanku mnogih kroničnih bolesti, uključujući pretilost i osteoporozu. U ovom se preglednom članku opisuju promjene uslijed modernog načina prehrane, s posebnim osvrtom na vrste i količine konzumirane masti. Također se objašnjavaju nedostatci moderne prehrane s obzirom na upalne procese te međusobna povezanost između pretilosti i upalnih procesa, koji su usto i poveznica između pretilosti i osteoporoze. U članku se iznose saznanja o tome da pretjerana konzumacija omega-6 masnih kiselina uz nedostatnu konzumaciju omega-3 masnih kiselina dovodi do kronične upale niskoga stupnja i povišenih vrijednosti reaktivnih kisikovih čestica (ROS), a time i do pomaka u mezenhimskih matičnih stanica (prekursora osteoblasta i adipocita) prema povećanoj adipogenezi i smanjenoj osteoblastogenezi. Uz povećanu sintezu upalnih citokina zbog pretilosti, moderna prehrana s nepovoljnim omjerom omega-6 i omega-3 kiselina u korist prvih nastavlja poticati pretilost i osteoporozu jer održava i pogoršava kroničnu upalu.

Osteosarcopenic Obesity Syndrome: What Is It and How Can It Be Identified and Diagnosed?

Conditions related to body composition and aging, such as osteopenic obesity, sarcopenia/sarcopenic obesity, and the newly termed osteosarcopenic obesity (triad of bone muscle and adipose tissue impairment), are beginning to gain recognition. However there is still a lack of definitive diagnostic criteria for these conditions. Little is known about the long-term impact of these combined conditions of osteoporosis, sarcopenia, and obesity in older adults. Many may go undiagnosed and progress untreated. Therefore, the objective of this research is to create diagnostic criteria for osteosarcopenic obesity in older women. The proposed diagnostic criteria are based on two types of assessments: physical, via body composition measurements, and functional, via physical performance measures. Body composition measurements such as T-scores for bone mineral density, appendicular lean mass for sarcopenia, and percent body fat could all be obtained via dual energy X-ray absorptiometry. Physical performance tests: handgrip strength, one-leg stance, walking speed, and sit-to-stand could be assessed with minimal equipment. A score could then be obtained to measure functional decline in the older adult. For diagnosing osteosarcopenic obesity and other conditions related to bone loss and muscle loss combined with obesity, a combination of measures may more adequately improve the assessment process.

Osteosarcopenic obesity in women: impact, prevalence, and management challenges

Osteosarcopenic obesity syndrome (OSO) has recently been identified as a condition encompassing osteopenia/osteoporosis, sarcopenia and obesity. OSO is especially deleterious in older adults (even if they are not obese by conventional measures), due to age-related redistribution of fat and its infiltration into bone and muscle. Osteoporosis and bone fractures in elderly increase the risk of sarcopenia, which, through decreased mobility, increases the risk of more falls and fractures, creating a vicious cycle. Obesity plays a dual role: to a certain extent, it promotes bone and muscle gains through mechanical loading; in contrast, increased adiposity is also a source of pro-inflammatory cytokines and other endocrine factors that impair bone and muscle. As the elderly population increases, changes in lifestyle to delay the onset of OSO, or prevent OSO, are warranted. Among these changes, dietary patterns and physical activity modifications are the first ones to be implemented. The typical Western diet (and lifestyle) promotes several chronic diseases including OSO, by facilitating a pro-inflammatory state, largely via the imbalance in omega-6/omega-3 fatty acid ratio and low-fiber and high-processed food consumption. Nutritional modifications to prevent and/or alleviate the OSO syndrome include adequate intake of protein, calcium, magnesium and vitamin D and increasing consumptions of foods containing omega-3 polyunsaturated fatty acids and fiber. Certain types of physical activity, often decreased in overweight/obese women and in elderly, might preserve bone and muscle, as well as help in reducing body fat accrual and fat infiltration. Habitual daily activities and some alternative modes of exercise may be more appropriate for older adults and play a crucial role in preventing bone and muscle loss and maintaining optimal weight. In conclusion, older adults who suffer from OSO syndrome may benefit from combined efforts to improve diet and physical activity, and such recommendations should be fostered as part of public health programs.

Micronutrient Intake in the Etiology, Prevention and Treatment of Osteosarcopenic Obesity

BACKGROUND Aging, chronic inflammation and/or many chronic conditions may result in loss of bone, loss of muscle and increased adiposity, manifested either overtly (overweight) or furtively as fat infiltration into bone and muscle. This combined condition has been identified as osteosarcopenic obesity. Micronutrients are required, not just to prevent deficiency diseases, but for optimal health and metabolic homeostasis. Further, micronutrients have multifunctional roles in the body. However, it is unknown if the micronutrient intake of the Western diet contributes to bone and muscle loss, increased adiposity, and ultimately osteosarcopenic obesity. OBJECTIVE The aim of this review is to examine the micronutrient intake using US National Health and Nutrition Examination Survey (NHANES) data, and explore if the insufficiencies, or excesses present contribute to the development of osteosarcopenic obesity in aging. METHOD First NHANES food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis. A literature search of PubMed and Medline for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each mineral and vitamin indicated as insufficient by NHANES. RESULTS NHANES data suggested phosphorus, calcium, magnesium, potassium, iron, and vitamins B6/B12/C/A/D/E and K were candidates for further evaluation. 170 articles were included. CONCLUSION While chronic single/multiple micronutrient insufficiency/excess is not studied in clinical trials, NHANES data suggest that they have existed for at least a decade. Examining the status and roles of those nutrients may be important to understanding the health issues associated with Western-type diets, including development of osteosarcopenic obesity.

Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake

Aging affects almost all physiological processes, but changes in body composition and body phenotype are most observable. In this review, we focus on these changes, including loss of bone and muscle and increase in body fat or redistribution of the latter, possibly leading to osteosarcopenic obesity syndrome. We also address low-grade chronic inflammation, prevalent in aging adults and a cause of many disorders including those associated with body composition. Changes in dietary intake and nutritional requirements of older individuals, that all may lead to some disturbances on tissue and organ levels, are discussed as well. Finally, we discuss the hormonal changes in the aging body, considering each of the tissues, bone, muscle and fat as separate endocrine organs, but yet in the continuous interface and communication with each other. Although there are still many unanswered questions in this field, this review will enable the readers to better understand the aging human body and measures needing to be implemented toward reducing impaired health and disability in older individuals.

Macronutrient Intake and Distribution in the Etiology, Prevention and Treatment of Osteosarcopenic Obesity

BACKGROUND Osteosarcopenic obesity, the combined deterioration of bone, muscle and fat tissues, could become the ultimate trajectory of aging. Aging stem cells are deregulated by low-grade chronic inflammation and possibly by diet. The metabolic shift of stem cells towards adipogenesis results in osteo obesity, sarco obesity and obesity. Macronutrients have numerous physiological functions but are regarded mainly for their energy contribution. Currently, no nutritional causes or treatment/prevention guidelines exist for osteosarcopenic obesity. OBJECTIVE The aim of this review is to assemble the evidence to elucidate if the macronutrient composition of the Western diet has an effect on the development of osteosarcopenic obesity. In view of the role of brain in locomotion a section examining the macronutrients as possible modulators of brain functioning was included. METHOD An extensive literature search of PubMed and Medline was conducted for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and energy, carbohydrate, protein and lipid, and brain. US National Health and Nutrition Examination Survey (NHANES) food intake data from 2002-2012 were obtained and transposed to Microsoft Excel for analysis. RESULTS NHANES data showed that energy imbalances in aging, excess high glycemic carbohydrate, lower protein intakes and low long chain polyunsaturated fat intakes may contribute to osteosarcopenic obesity. 135 articles were included in the review. CONCLUSION Early humans probably consumed a diet closer to what the human body was designed for; however, we do not know the ideal energy and macronutrient proportions for optimal health or for preventing/treating aging and osteosarcopenic obesity.

Can Unconventional Exercise be Helpful in the Treatment, Management and Prevention of Osteosarcopenic Obesity?

BACKGROUND Body composition changes occur with aging; bone and muscle mass decrease while fat mass increases. The collective term for these changes is osteosarcopenic obesity. It is known that conventional resistance exercise programs build/maintain lean mass and reduce fat mass. However, unconventional (to Western society/medicine) forms of exercise may be viable for the treatment/prevention of osteosarcopenic obesity. OBJECTIVE The purpose of this review is to assess relatively unconventional exercises for their efficacy in maintaining/improving bone and muscle mass and reducing fat mass. METHOD A literature search for unconventional exercise showed Tai Chi, yoga, Pilates, whole body vibration, electrical stimulation of muscle, and the Alexander Technique were considered alternative/ unconventional. A PubMed and Medline search for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each exercise was then conducted. RESULTS Tai Chi, yoga, and Pilates, in addition to whole body vibration, electrical stimulation of muscle, and the Alexander Technique are all considered low impact. Tai Chi, yoga, and Pilates not only physically support the body, but also increase balance and quality of life. The devices showed promise in reducing or preventing muscle atrophy in older people that are unable to perform conventional exercises. CONCLUSION Any exercise, conventional or otherwise, especially in sedentary older people, at risk of, or diagnosed with osteosarcopenic obesity may be better than none. Exercise prescriptions should suit the patient and the desired outcomes; the patient should not be forced to fit an exercise prescription, so all potential forms of exercise should be considered.

Utilizing Dietary Micronutrient Ratios in Nutritional Research May be More Informative than Focusing on Single Nutrients

The 2015 US dietary guidelines advise the importance of good dietary patterns for health, which includes all nutrients. Micronutrients are rarely, if ever, consumed separately, they are not tissue specific in their actions and at the molecular level they are multitaskers. Metabolism functions within a seemingly random cellular milieu however ratios are important, for example, the ratio of adenosine triphosphate to adenosine monophosphate, or oxidized to reduced glutathione. Health status is determined by simple ratios, such as the waist hip ratio, or ratio of fat mass to lean mass. Some nutrient ratios exist and remain controversial such as the omega-6/omega-3 fatty acid ratio and the sodium/potassium ratio. Therefore, examining ratios of micronutrients may convey more information about how diet and health outcomes are related. Summarized micronutrient intake data, from food only, from the National Health and Nutrition Examination Survey, were used to generate initial ratios. Overall, in this preliminary analysis dietary ratios of micronutrients showed some differences between intakes and recommendations. Principles outlined here could be used in nutritional epidemiology and in basic nutritional research, rather than focusing on individual nutrient intakes. This paper presents the concept of micronutrient ratios to encourage change in the way nutrients are regarded.