August 2020

Evaluation and Treatment of Osteosarcopenia in Older Adults

Key points

  • Osteosarcopenia is an under-recognized and undertreated chronic musculoskeletal syndrome among older adults as well as patients with chronic diseases, particularly diabetes mellitus and obesity
  • Osteosarcopenia is associated with increased frailty, falls and fracture risk, hospitalizations, and mortality
  • Bone density, lean muscle mass, and muscle function should be routinely evaluated in patients at high risk
  • Resistance and balance training, nutritional interventions, and osteoporosis medications are effective at curbing osteosarcopenia
  • If symptoms are related to an underlying chronic disease, it is important to address that disease in addition to treating the osteosarcopenia
  • See related Guest Perspective, Why Use Exercise

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By Aisha Cobbs, PhD

Bone loss (osteopenia/osteoporosis) and loss of muscle mass and function (sarcopenia) are two of the most prevalent chronic conditions among aging adults.1 However, the mention of osteosarcopenia might garner a few puzzled looks. This relatively new term describes a geriatric syndrome in which osteopenia/osteoporosis and sarcopenia overlap in the same individual.2

For most  practicing clinicians, osteoporosis is somewhat more recognized than sarcopenia, said Jad G. Sfeir, MD, Assistant Professor of Medicine at Mayo Clinic and Kogod Scholar at the Robert and Arlene Kogod Center on Aging. Still, screening and recognition of osteoporosis remains suboptimal, but it is better than sarcopenia alone. So, it is not surprising that there is limited recognition of osteosarcopenia in the clinical setting.

Elevating awareness of osteosarcopenia is a global health priority because the co-existence of both osteopenia/osteoporosis and sarcopenia is associated with increased frailty, falls and fracture risk, hospitalizations, and mortality.3 Like other age-related chronic diseases, the prevalence of osteosarcopenia is expected to surge with the dramatic rise in the aging global population.4

Pathophysiology

Genetics, physical inactivity, inflammation, hormone imbalances, and chronic conditions contribute to the age-related association between muscle and bone loss (Figure 1).2,3,5,6 The pathophysiology of osteosarcopenia involves a complex interplay between the muscle, bone, and fat tissue.7  Our current understanding of osteosarcopenia is that adipose tissue is capable of secreting adipokines that induce apoptosis of myocytes and osteocytes; this ability to cause the death of muscle and bone cells and thereby suppress remodeling and new growth means obesity plays a bigger role than initially thought.8

With aging, there is unfavorable redistribution of adipose tissue from the subcutaneous to visceral compartments, including increased infiltration of adipose tissue into the muscle and bone, said Jasminka Ilich-Ernst, PhD, RDN, FACN, Professor of Nutrition in the Institute for Successful Longevity at Florida State University. Ilich-Ernst and her colleagues first coined the term osteosarcopenic obesity in 2014 to describe how these alterations in body composition (ie, muscle, bone, and adipose tissue) result in altered bone metabolism and progressive sarcopenia (Figure 2).9,10 Visceral adipose tissue contributes to low-grade chronic inflammation by secreting cytokines and other inflammatory mediators that negatively impact bone and muscle health in aging adults.7 She later refined the term, suggesting that osteosarcopenic adiposity more accurately describes the disorder.6 This discussion will use the term osteosarcopenia, but LER will continue to bring updates on the evolution of the science of this disorder.

The effects of chronic low-grade inflammation observed in patients with osteosarcopenia can extend beyond deteriorating bone and muscle health, said Ilich-Ernst. In the setting of inflammation, the ill effects of comorbidities may be compounded and pro-inflammatory mediators can trigger over-activation of the immune system (the so-called “cytokine storm”) in response to viral infections such as COVID-19, she noted.

Clinical Evaluation

Figure 1. Major Risk Factors for Osteosarcopenia2,3,4,5,6

1. Aging

2. Female sex

3. Genetic polymorphisms of the genes associated with muscle atrophy and bone loss, eg:

a. Glycine-N-acyltransferase (GLYAT)

b. Methyltransferase like 21C (METTL21C)

c. Peroxisome proliferator-activated receptor

d. Gamma coactivator 1-alpha (PGC-1α)

e. Myocyte enhancerfactor-2 (MEF2C)

4. Chronic inflammation

5. Fat infiltration of muscle and bone

6. Endocrine disorders

a. Diabetes

b. Abnormal thyroid function

c. Low levels of vitamin D, sex hormones, growth hormone, or insulin-like growth factor

7. Chronic kidney disease

8. Rheumatoid arthritis

9. Corticosteroid use

10. Chronic stress

11. Smoking

12. High alcohol consumption

13. Sedentary lifestyle/poor mobility

14. Malnutrition and obesity

15. Living in a residential aged care facility

Risk factors for the condition are detailed in Figure 1.2,3,5,6 Clinical assessment of osteosarcopenia should be routinely performed in patients at high risk.3 Since the prevalence of osteosarcopenia is high in older adults, it is recommended that it be evaluated as a part of the comprehensive geriatric assessment.3 When evaluating patients for osteosarcopenia, it is important to take a comprehensive history including medical, social, falls, fractures, and medication histories.3 It is also important to inquire about routine physical activity and whether they are experiencing exhaustion, said Mayo’s Sfeir.

Physical assessment. In addition to taking a comprehensive history, there are 3 things that Sfeir said need to be assessed: bone metabolism, muscle mass, and muscle function (Figure 2).3 He also noted that there are cost-effective and time-efficient tools that can be used to evaluate osteosarcopenia, even in the primary care setting.

Measuring bone density using dual X-ray absorptiometry (DEXA) is an inexpensive, easy way to evaluate bone metabolism with minimal radiation exposure.11

To evaluate patients for sarcopenia, clinicians must assess both muscle mass and muscle function.2 Measuring muscle mass can be challenging because many of the tools that are used to assess muscle mass are not widely available clinically. We used to think that weight and body mass index (BMI) were very good tools because they are easy to do, but Sfeir explained, it turns out that weight and BMI alone provide measurement of overall mass, not lean mass. Instead, DEXA can also be used to obtain an accurate estimate of lean body mass and appendicular lean mass.3

Grip strength, sit to stand, and the timed up and go (TUG) tests can be readily performed in an office setting to assess muscle function.2 Grip strength has been correlated very well with overall muscle mass and muscle function in large studies and it is an easy way to detect sarcopenia in the clinic, said Sfeir. Standing up alone requires a lot of muscle function from the proximal muscles of the neck, so the sit to stand test gives us a lot of information about that, he continued. The TUG provides a general indication of lower muscle strength.

If a clinician does not have access to a DEXA machine, they can use the patient’s comprehensive history, BMI, and muscle function assessments to detect sarcopenia, Ilich-Ernst noted. Sfeir suggests that in situations like these, standardized frailty tests can also give clinicians indirect but useful information about muscle performance.

Treatment

Figure 2. Conceptual model of bone, muscle, and fat tissues in healthy and diseased states: osteosarcopenic obesity is the most advanced stage resulting from aging or other compromised impairment in bone, muscle, and adipose tissue. From reference 9; use is per Creative Commons Attribution License.

Physical activity, nutrition, and lifestyle interventions are the cornerstone of osteosarcopenia treatment and can help to reduce adiposity as well, said Ilich-Ernst. The key is to individualize treatment based on the needs of the patient.

In addition to non-pharmacological treatment strategies, several pharmacotherapies are approved for the treatment of osteoporosis including, antiresorptive agents (denosumab, bisphosphonates), anabolic agents (teriparatide, abaloparatide), sclerostin inhibitors (romosozumab), and hormonal agents (hormone replacement therapy, selective estrogen receptor modulators).3 Currently, there are no approved pharmacotherapies for sarcopenia, although several agents are currently under investigation.3

Physical activity. Muscles and bones are dynamic tissues that can adapt to changes in mechanical load by modifying their mass and strength. Thus, mechanical stimulation is necessary to prevent muscle degradation and bone resorption.11 Low-intensity physical activity, including aerobic, flexibility, strength training, and resistance and balance exercises are recommended to improve or maintain body composition, bone mineral density, as well as muscle strength and quality.4 These activities have also been shown to reduce age-related inflammation and fall risk in older adults.4

Although any physical activity is good, it is important that the comprehensive treatment plan include supervised physical activity, especially in older adults who have some form of morbidity or limitation, said Sfeir. Sometimes the patients that are being treating for osteosarcopenia also have osteoarthritis which may limit what they can do. That is why it is important to refer patients to a physical therapist who can assess their baseline abilities and identify activities that they can do at home, he added.

For patients with osteosarcopenia, the goals of physical therapy would include strengthening the muscles that support the skeleton in order to minimize injury to the bones, explained Kelli McLaren, PT, DPT, SCS, CMTPT, a physical therapist at Sovereign Rehabilitation in Canton, Georgia. The plan would also focus on minimizing the risk of falls and bone injury by improving balance and proprioception. Most patients with osteosarcopenia require at least 6 to 12 weeks of physical therapy, although osteoporotic bone fractures may take longer to treat.

Many times, in the clinic we are treating injuries that are result of the patient having osteoporosis, so our aim is to help them return to their prior level of function as much as possible, explained McLaren. For example, if an individual falls and fractures their ankle, our first goal would be to improve strength and range of motion around the ankle specifically. The patient’s functional goals and progress are reassessed every visit and gradually, the focus would shift to progressively strengthening the whole leg. Since the patient has osteoporosis, it is important to work slowly and safely to strengthen the stabilizing muscles that support the spine and lower extremities, McLaren elaborated.

Nutritional Intervention. Newly diagnosed patients are referred to a dietician to help identify nutritional deficiencies and set up a nutrition plan that is individualized to their needs and dietary intake.7 Nutritional interventions may include increasing protein intake, vitamin D and/or calcium supplementation, or limiting high glycemic index foods.2,7 The goal of nutrition management is to identify a nutrition plan that can improve muscle and bone mass, but it is just as important that the plan be something that the patient can follow long-term, said Sfeir.

Prognosis

Figure 3

The combination of physical activity, nutritional interventions, and appropriate pharmacotherapies can halt osteosarcopenia, and can improve it to a certain extent, but it is unlikely that the muscle or bone mass can be restored to peak levels, said Ilich-Ernst.

These interventions can improve metabolism and limit age-related symptoms, agreed Sfeir. However, the extent of reversibility depends on what caused the disease. Therefore, if symptoms are related to an underlying chronic disease, it is important to address that disease in addition to treating the osteosarcopenia.

Studies have shown that the positive effects of exercise on bone density and muscle strength disappear in as little as 6 months in the absence of regular activity.4 Therefore, long-term outcomes in patients with osteosarcopenia are better if they have an at-home exercise program that can continue beyond the few weeks or months of intensive therapy, commented Sfeir. When discussing treatment plans with patients, it is important to emphasize the need for continuous training and to inform them that if they stop training, the muscle mass and muscle function can revert to sarcopenia and frailty, he added.

Clinical Pearls

Osteosarcopenia is a major cause of morbidity and mortality among older adults; however, it is a treatable disorder that can be effectively diagnosed and managed by specialists and non-specialists alike. Recognizing osteosarcopenia in the office is especially important, even when specialized tools are not available, said Sfeir. He also noted that initiating the discussion with patients can set the basis for future intervention. If you work with the patient to individualize management based on what they can do, you are setting them up for success in achieving their goals.

Aisha Cobbs, PhD, is a medical writer in the Washington, DC, area.

REFERENCES
  1. Kirk B, Al Saedi A, Duque G. Osteosarcopenia: A case of geroscience. Aging Med (Milton). 2019;2(3):147-156.
  2. Fatima M, Brennan-Olsen SL, Duque G. Therapeutic approaches to osteosarcopenia: insights for the clinician. Ther Adv Musculoskelet Dis. 2019;11:1759720X19867009.
  3. Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers. J Cachexia Sarcopenia Muscle. 2020;11(3):609-618.
  4. Arazi H, Eghbali E. Osteosarcopenia and physical activity. Ann Sports Med Res. 2018; 5(1): 1130.
  5. Hassan EB, Duque G. Osteosarcopenia: A new geriatric syndrome. Aust Fam Physician. 2017;46(11):849-853.
  6. Ilich JZ, Gilman JC, Cvijetic S, Boschiero D. Chronic stress contributes to osteosarcopenic adiposity via inflammation and immune modulation: the case for more precise nutritional investigation. Nutrients. 2020;12(4):989.
  7. Kelly OJ, Gilman JC, Boschiero D, Ilich JZ. Osteosarcopenic obesity: current knowledge, revised identification criteria and treatment principles. Nutrients. 2019;11(4):747.
  8. Al Saedi A, Bani Hassan E, Duque G. The diagnostic role of fat in osteosarcopenia. J Lab Precis Med 2019;4:7.
  9. Ilich JZ, Kelly OJ, Inglis JE, Panton LB, Duque G, Ormsbee MJ. Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res Rev. 2014;15:51-60.
  10. Ilich JZ, Kelly OJ, Inglis JE. Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed? Curr Gerontol Geriatr Res. 2016;2016:7325973.
  11. Hirschfeld HP, Kinsella R, Duque G. Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int. 2017;28(10):2781-2790.

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