Age

Sarcopenia and osteoporosis are age-related diseases by definition . The mean age of the subjects with osteosarcopenia is close to 80 years (79–82 years), as observed in most studies. People in this age group have a significant increase in the incidence of fractures. This significant increase is caused by the greater physical functional loss resulting from sarcopenia, and the lower BMD observed in osteosarcopenic patients as compared to older persons with sarcopenia or osteoporosis only .

Sex

Osteosarcopenia occurs more frequently in women than in men. Studies have shown variation between 55% and 65% of prevalence in women . The association with the female is mainly due to the estrogenic deprivation of menopause, which causes a marked decrease in muscle strength in women . The lower muscle strength promotes less mechanostatic action, decreasing the stimulus on bone growth and, consequently, more significant loss of BMD, contributing to the incidence of osteosarcopenia.

Obesity

Obesity, i.e., excess body fat, usually defined as body mass index (BMI)⩾ 30 kg/m ² , is a major public health problem and is well recognized as a risk factor for morbidity and mortality in older adults . Aging is associated with significant changes in body composition with a substantial reduction in fat-free mass and muscle mass and an increase in visceral fat . Given the age-related changes in body composition, sarcopenia often coexists with an increase in fat mass. Visceral fat and muscle mass are known to be interrelated from a pathogenic point of view and are reported to share common inflammatory pathways . In addition, sarcopenia reduces physical activity, resulting in decreased energy expenditure, leading to an increased risk of obesity . Alternatively, visceral fat induces inflammation, contributing to osteoporosis and sarcopenia . The interplay between sarcopenia and rising trends in obesity in an aging population is emerging as a paramount public health concern in the older population. The term sarcopenic obesity was first introduced by Baumgartner and is defined by the combination of sarcopenia and obesity. Obesity and sarcopenia may act synergistically; sarcopenic obesity may have a greater effect on metabolic disorders and mortality, disability, or physical function as outcomes than either obesity or sarcopenia alone . Therefore, screening people with obesity for osteosarcopenia is indicated to prevent unfavorable outcomes of older adults.

Fat infiltration

Since BMI does not distinguish between fat mass and fat-free mass, which have opposing effects on the risk of morbidity and mortality, the use of BMI in older persons may have limitations . Therefore, to fully understand the impact of obesity on older persons, it is essential also to take both fat mass and lean mass into account. Several studies have observed that osteosarcopenic individuals present a high percentage of fat independent of BMI . There is still no consensus as to the percentage of better specificity and sensitivity for these patients. At present, high fat is present when it is above 30% or 40% or the percentage body fat percentage by the squared height is equal to or above the upper quintile of the sample.

Low body weight

Low body weight, defined by low BMI, is associated with sarcopenia . The few studies that evaluated the BMI of older subjects with osteosarcopenia showed that the mean BMI of these individuals is lower when compared to individuals with sarcopenia and osteoporosis only. However, due to the ethnic and gender variety of study populations, there is some discrepancy as to the mean that can best characterize osteosarcopenia, since they ranged from 20.7 (3.5) kg/m ² in Asian elderly with hip fracture to 27.2 (6.2) kg/m ² in a population of community-dwelling older persons with a high prevalence of obesity .

Sedentary lifestyle/poor mobility

Both bone and muscle are adaptive, modifying their mass and strength in response to mechanical loading. Therefore, mechanical stimulus is essential for the health of both tissues, and thus, decreased levels of physical activity may shift the delicate balance in favor of muscle degradation and bone resorption . Physical activity diminishes with aging, with up to 80% of waking hours spent sedentary in older adults , leading to a loss of mechanical loading and associated bone and muscle loss . Low mobility is a prevalent and specific clinical feature among the osteosarcopenic population. The risk of loss of mobility was about three times higher among osteosarcopenic patients than the control group, whereas people with sarcopenia had no significant association with loss of mobility .

Malnutrition

Caloric intake diminishes by around 25% between the ages of 40 and 70 , with reduced vitamin D levels and protein intake correlated with declining muscle strength . Vitamin D deficiency also increases the risk of falls and fractures through its multiple effects on muscle and bone . Malnutrition was described in a study with the Mini-Nutritional Assessment (MNA) tool. In this study, osteosarcopenic individuals present a twofold higher risk for malnutrition (MNA < 12) than individuals in the control group .

Smoking

Smoking may have detrimental effects on the skeletal system. Recent evidence demonstrates tobacco smoking causes an imbalance in the mechanisms of bone turnover, leading to lower bone BMD making bone vulnerable to osteoporosis and fracture . Similarly, components of cigarette smoke enter the bloodstream and reach the skeletal muscles of smokers and accelerate muscle wasting . A metaanalysis of 12 studies (22,515 participants) indicated that cigarette smoking as an isolated factor might contribute to the development of sarcopenia. Therefore, cigarette smoking should be counted among the risk factors of osteosarcopenia .

Alcohol consumption

Alcohol is a significant risk factor for osteoporosis, with an intake of ≥ 3 units of alcohol/day increasing fracture risk in a dose-dependent fashion .

Glucocorticoids

The increased incidence of various diseased states during aging is associated with the hypersecretion of glucocorticoids . Glucocorticoid-associated atrophy appears to be specific to type II or phasic muscle fibers. In a study of controlled hypercortisolemia in healthy men , experimental inactivity increased the catabolic effect of glucocorticoids, suggesting that an absence of mechanical signals potentiates the impact. The mechanism of glucocorticoid-induced atrophy may involve an upregulated expression of myostatin and glutamine synthetase, the latter via the glucocorticoid receptor’s interaction with the glutamine synthetase promoter . Glucocorticoids inhibit the physiological secretion of growth hormone and appear to induce IGF-I activity in target organs . Also, prolonged use of systemic glucocorticoids (i.e., at least three months cumulative use during the preceding year at a prednisone-equivalent dose ≥ 7.5 mg daily) increases the risk of fracture independent of BMD .

Low vitamin D

Vitamin D has been considered a key regulator of bone metabolism and calcium and phosphorus homeostasis through negative feedback with the parathyroid hormone . It is also well established that vitamin D deficiency is a risk factor for osteoporosis in older adults. A large and growing body of evidence suggests that vitamin D is necessary for bone tissue and calcium metabolism . Approximately 1 billion, mostly older persons, worldwide have vitamin D deficiency . The prevalence of low vitamin D concentrations in subjects older than 65 years of age has been estimated at approximately 50% . Similarly, there is an age-dependent reduction in vitamin D receptor expression in skeletal muscle . Prolonged vitamin D deficiency has been associated with severe muscle weakness, which improves with vitamin D supplementation . Interestingly, muscle biopsies performed before and after vitamin D supplementation have documented an increased number and sectional area of type II (or fast) muscle fibers . More comprehensive knowledge of vitamin D-related mechanisms may provide a helpful tool for preventing muscle atrophy in older persons (sarcopenia).

Hypogonadism (male)

In males, levels of testosterone decrease by 1% per year, and those of bioavailable testosterone by 2% per year from age 30 . In women, testosterone levels drop rapidly from 20 to 45 years of age . Testosterone increases muscle protein synthesis , and its effects on muscle are modulated by several factors, including genetic background, nutrition, and exercise . Numerous studies of treatment with testosterone in older persons have been performed over the past few years . In 1999, Snyder et al. suggested that increasing the level of testosterone in older men to that seen in young men increased muscle mass but did not result in functional gains in strength. Systemic reviews of the literature have concluded that testosterone supplementation attenuates several sarcopenic symptoms, including decreases in muscle mass and grip strength . For instance, a recent study of 6 months of supraphysiological dosage of testosterone in a randomized placebo-controlled trial reported increased leg lean body mass and leg and arm strength . Although there are significant increases in strength among older males given high doses of testosterone, the potential risks may outweigh the benefits. Risks associated with testosterone therapy in older men include sleep apnea, thrombotic complications, and the increased risk of prostate cancer .

Menopause (female)

Menopause is a natural part of aging, and it encompasses the loss of ovarian reproductive function. Osteoporosis is a common, asymptomatic postmenopausal disease that substantially impacts the quality of life of older women. Osteoporosis-related fractures are one of the causes of disability among the older population . One in two postmenopausal women will have an osteoporotic fracture in their lifetime .

It has been hypothesized that menopause transition and the subsequent decline in estrogen may play a role in muscle mass loss . Van Geel et al. reported a positive relationship between lean body mass and estrogen levels. Similarly, Iannuzzi-Sucich et al. observed that muscle mass is correlated significantly with plasma estrone and estradiol levels in women. The mechanisms by which a decrease in estrogen levels may have a negative effect on muscle mass are not well understood but may be associated with an increase in proinflammatory cytokines, such as TNF-α and IL-6, which might be implicated in the apparition of sarcopenia . Furthermore, estrogen could directly affect muscle mass since it has been shown that skeletal muscle has estrogen beta-receptors on the cell membrane . Therefore, a direct potential mechanistic link could exist between low estrogen levels and a decrease in protein synthesis.

Low growth hormone

Growth hormone (GH) is a single-chain peptide of 191 amino acids produced and secreted mainly by the somatotrophs of the anterior pituitary gland. GH coordinates the postnatal growth of multiple target tissues, including skeletal muscle . Indeed, circulating GH levels decline progressively after 30 years of age at a rate of ∼ 1% per year . In aged men, daily GH secretion is 5- to 20-fold lower than in young adults . The age-dependent decline in GH secretion is secondary to a decrease in GHRH and an increase in somatostatin secretion . There is evidence that the age-associated decline in GH levels in combination with lower IGF-I levels contributes to the development of sarcopenia . The effects of GH administration on muscle mass, strength, and physical performance are still under debate . In animal models, GH treatment effectively inhibits sarcopenic symptoms such as muscle atrophy and decreases in protein synthesis, particularly in combination with exercise training . The effect of GH treatment on older subjects is controversial. Some groups demonstrated an improvement in strength after long-term administration (3–11 months) of GH . In contrast, many researchers have found that muscle strength or muscle mass did not improve on supplementation with GH .

Hyperparathyroidism

Hyperparathyroidism is due to increased parathyroid gland activity, which leads to osteoporosis with related fractures . Proximal muscle weakness due to type II muscle fiber atrophy can be seen in association with severe bone disease (such as osteoporosis) . High serum levels of parathyroid hormone have been recently associated with osteosarcopenia independently of serum vitamin D or renal function (summarized in Chapter 8 ).

Living in a residential care facility

Dependent older adults pose a particular challenge for researchers because advanced functional and cognitive impairment may limit their capacity to perform tests, especially for speed and strength. As the population ages, a greater number of older adults will need residential support such as residential care facility (RACF). RACF residents are often frail since their multiple physical and cognitive deficits place them at high risk of falls, disability, and death . The fracture rate for adults living in RACF is two to four times that of adults of a similar age living in the community, and one-third of older adults who experience hip fracture are residents in RACF .

A systematic review and metaanalysis published in 2017 by Shafiee et al. addressed the worldwide prevalence of sarcopenia but excluded studies carried out in hospitals or nursing homes for older adults. The prevalence of sarcopenia was shown to be higher in RACF residents. A review followed the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP) , described prevalence values of 1%–29% among older adults living at home, 14%–68% among those in RACF, and 10% among people hospitalized in acute care . Another review included studies that evaluated the prevalence of sarcopenia among older adults (aged ≥ 60 years) living in RACF. Forty-four studies were identified, of which 21 studies were included after applying eligibility criteria. The reported prevalence of sarcopenia ranged widely between 17.7% and 73.3% in RACF and between 22% and 87% in assisted-living facilities . Therefore, it is critical to identify RACF residents with osteosarcopenia.

Previous fragility fracture

History of fragility fracture is associated with osteoporosis and sarcopenia. In a recent study, 70 out of 139 hip fracture patients (50.36%) were diagnosed with sarcopenia. Hip fracture patients with sarcopenia also have insufficient activity of daily living and a lower quality of life than patients without sarcopenia before the injury and 6 months after the operation . Clinicians should examine people with a history of fragility fracture for sarcopenia and osteoporosis (if not diagnosed already).

Frailty

The odds of frailty are significantly higher in osteosarcopenic patients than those with osteoporosis or sarcopenia alone . Bone and muscle loss also may be tightly linked to the risk of frailty as shown in a 2015 study conducted in China in which osteosarcopenia was found in 26.3% of men and 38.5% of women with frailty and only in 1.6% and 1.9% of nonfrail men and women, respectively .

Measurement protocol

The American Society of Hand Therapists (ASHT) recommends standardized positioning: patient seated, shoulders adducted and neutrally rotated, elbow flexed at 90°, forearm in neutral, and wrist between 0° and 30° of dorsiflexion . Different methods of instruction and/or verbal encouragement can affect the patients’ performance and thus introduce measurement error . Mathiowetz et al. have a set of standardized instructions: “I want you to hold the handle like this and squeeze as hard as you can.” The examiner demonstrates and then gives the dynamometer to the subject. After the subject is positioned appropriately, the examiner says, “Are you ready? Squeeze as hard as you can.” As the subject begins to squeeze, the examiner says, “Harder!… Harder!… Relax” .

Sarcopenia cut-off points for grip strength vary according to the sarcopenia definition used. Table 1 summarizes the cut-off points for EWGSOP2, Asian Working Group for Sarcopenia, and The Foundation for the National Institutes of Health (FNIH) .