Involutional Osteoporosis: Sarcopenia, Frailty Syndrome and Falls



Fig. 34.1
Based on bone mineral density (BMD), a majority of women with fractures do not have osteoporosis (WHO) (Adjusted after: Siris et al. [34])



The ageing process is associated with irreversible decrease of function and anatomical involution of the neuro-musculo-skeletal system as a whole [14, 25]. Therefore our efforts should not be focused only on increase in bone density or changes in its architecture, and a more comprehensive approach is required, perceiving a geriatric patient as a whole. Thus, the aim should not be a mere reinforcement of the bone stock but primarily reduction of the risk of falls (“no fall, no fracture” concept). A recent Canadian study shows that although prescription of antiosteoporotic drugs differs across provinces up to four times, the global incidence of femoral neck fractures is the same [7].


34.1 Sarcopenia


In 1989, Irwin Rosenberg proposed the term “sarcopenia” to describe age-related decrease of muscle mass. At the same time, the processes of decrease of bone and muscle mass are closely interconnected at several levels, including primarily the functional and mechanical interaction, systemic agents – hormones, cytokines, etc., co-participating in both processes and common genetic factors. Orwoll calls it a “crosstalk” between muscle and bone. These two processes have a common underlying basis, namely, imbalance. In osteoporosis it is imbalance between resorption (RANK-RANKL system) and formation (Wnt signalling pathway), while in sarcopenia it is imbalance between synthesis (phosphatidylinositol-3 system) and muscle degradation (myostatin, sexagens, decreased activity of the growth hormone axis, etc.).

As people age, they lose 20–30 % of muscle mass; at the age over 90, it is up to 50 %. Women lose on average 1 kg and men 2 kg of muscle mass per age decade. Incidence of sarcopenia is reported in about 5–13 % of persons between 60–70 years of age and in about 10–50 % of individuals older than 80 years. Similarly as osteoporosis and its consequences, also sarcopenia and its consequences have a significant impact on the health status of geriatric patients, representing a huge economic burden. For example, in the USA, the annual cost of consequences of osteoporotic fractures was calculated at 16.3 billion USD while that of sarcopenia at as much as 18.5 billion USD (Fig. 34.2). Sarcopenia increases twice the risk of falls and three times the risk of limitation of self-care capacity of patients [8, 11]. Analyses of groups of geriatric patients have shown that an absolute majority of them suffer both from sarcopenia and osteoporosis. Therefore this condition is sometimes called “sarcoporosis”. One of the priorities in the near future, which is currently intensively addressed, will be adoption of definition of sarcopenia, similarly as in osteoporosis.

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Fig. 34.2
Sarcopenia – consequences (cost in USD) (Modified after: Janssen et al. [18])

Sarcopenia is certainly not a mere synonym for decrease of muscle mass. Its other symptoms include also functional disorders – decrease of muscle strength and of physical performance.

Muscle mass decrease seems to be responsible for up to 60 % of decrease of physical performance and impaired ability of patients with sarcopenia to perform activities of daily living, the rest being the question of muscle strength and quality. There are a number of methods for measuring muscle mass, strength and performance that are used primarily experimentally, although several procedures are routinely used in the clinical practice (Table 34.1). The simplest and best available combination of methods is measuring muscle mass by DXA, muscle strength by handgrip and physical performance by the test of the usual gait speed. Similarly as osteoporosis categorized into mild, more severe osteopenia and osteoporosis, sarcopenia may be divided into similar stages (Table 34.2).


Table 34.1
Evaluation of muscle mass, strength and performance






















































Variable

Experimental examinations

Clinical examinations

Muscle mass

Computer tomography (CT)

BIA

Magnetic resonance imaging

DXA

Dual energy X-ray absorptiometry (DXA)

Anthropometry

Bioimpedance analysis (BIA)
 

Total or partial body potassium per fat-free soft tissue
 

Anthropometry
 

Muscle strength

Handgrip strength measurement by dynamometer

Handgrip strength measurement by dynamometer

Knee flexion/extension
 

Peak expiratory flow
 

Physical performance

Short physical performance battery, SPPB

SPPB

Usual gait speed

Usual gait speed

Timed get-up-and-go test

Get-up-and-go test

Stair climb power test
 


Modified after Gojda [16]



Table 34.2
EWGSOP conceptual stages of sarcopenia




























Stage

Muscle mass

Muscle strength

Physical performance

Pre-sarcopenia

   

Sarcopenia


↓ or ↓

Severe sarcopenia





Modified after Cruz-Jentoft et al. [8]

Sarcopenia has also very similar etiopathogenetic causes as osteoporosis. It may be primary, age related, secondary, associated with limited mobility due to physical inactivity, or associated diseases or malnutrition.

Sarcopenia is clinically well identifiable and may be suspected in persons with asthenic habitus. A separate group, which poses a clinical problem, are obese individuals who also suffer from decrease of muscle mass for some reason, but in them this problem is often considered much later (sarcopenic obesity).


34.2 Sarcopenia: Causes





  1. (a)


    Primary – age related

     

  2. (b)


    Secondary

     




  • Activity related – bed rest, sedentary lifestyle, deconditioning or zero-gravity conditions


  • Disease associated – advanced organ failure, inflammatory disease, malignancy or endocrine disease


  • Nutrition associated – malabsorption, gastrointestinal disorders or use of medications that cause anorexia

In terms of interaction of sarcopenia and osteoporosis, the most alarming clinical situation occurs in patients with femoral neck fracture. It has been demonstrated that a ten-day bed rest in these patients may lead to a loss of up to 1.5 kg of lean body mass (LBM) which from the functional viewpoint equals a 15 % loss of muscle strength of lower extremities. No surprise, these patients have a poor prognosis unless they are promptly operated on, mobilized and supplied with adequate amounts of substrates for protein synthesis.

The effect of pharmacological treatment on sarcopenia remains questionable. The candidate medications are included in Table 34.3: however, practical use and available evidence-based data currently relate only to vitamin D and alfacalcidol [9, 10, 27, 29, 32, 33]. An essential therapeutic and preventive measure is regular physical activity. As mentioned above, limited mobility or immobility leads quite rapidly to significant progression of sarcopenia and subsequently, in the longer run, also to decrease in BMD (osteopenia follows sarcopenia). In this context, the old adage holds true: use it or lose it.


Table 34.3
Pharmacological treatment of sarcopenia










































































Drugs

Observational studies

RCT

Safety/tolerability

Availability

Indication for sarcopenia

Testosterone

Yes

Yes

Prostate cancer, erythrocytosis, hyperviscosity, sleep apnoea, CV events

Yes

Men with androgen deficit and low testosterone level

SARM

No

Yes

Elevated ALT/AST, haematocrit,

lipid profile

No

No

GH

Yes

Yes

Arthralgia, gynecomastia, soft tissue oedema, DM

Yes

No

Ghrelin

Yes

Yes

Swelling, myalgia, increased appetite

No

No

GH secretagogue

No

Yes

Fatigue, insulin resistance, insomnia, elevated ALT/AST

No

No

Oestrogens

Yes

Yes

VTE, CV disease, stroke, breast cancer

Yes

No

Leptin

Yes

No

?

No

No

Vitamin D

Yes

Yes

Low toxicity

Yes

Possible

Both sarcopenia and osteoporosis are age-related processes, resulting from decreased muscle mass and quality, with similar etiological moments and almost the same pathogenesis. They also have similar consequences for human health – increased risk of falls and fractures. Sarcopenia is therefore currently intensively investigated by a whole number of research teams worldwide; in Europe it is primarily the European Working Group on Sarcopenia in Older People (EWGSOP).


34.3 Frailty Syndrome


Frailty syndrome (FS) is one of the core geriatric syndromes, which is considered a cornerstone (holy grail or raison d’etre) of the current geriatric medicine. Its principle is accumulation of age-related deficits compromising the ability to withstand stressors and to maintain immune system homeostasis. Physiological reserves are decreasing with the increasing risk of adverse consequences of ageing. To put it simply, it is a process of accelerated, unsuccessful ageing [12, 41]. Biological age is naturally influenced by a number of various deficits acquired by a particular person during the whole life and may largely vary between individuals. Accumulation of deficits and handicaps is growing exponentially at the end of life. FS is a vulnerable state of an individual associated with a high risk of an external trigger event provoking a cascade of consequences with adverse effects, complications (falls, injuries, recurrent infections, repeated hospital stay, worse convalescence, a higher risk of iatropathogenic factors), such as immobility, inability to perform activities of daily living or death in the worst case [21, 41, 42]. On the other hand, if properly detected, this state may be successfully treated and other problems may be effectively prevented. Thus, it is sort of “therapeutic window” in the ageing process associated with possible reversibility. Chronologically, it proceeds from the “frailty phenotype” through “prefrail” phase to the actual FS and its potential consequences (Fig. 34.3). The FS principle is based on the concept that human beings are not only a sum of individual parts and that it is necessary to evaluate comprehensively their state and risks. This phenomenon goes against the mainstream of the current atomized and overspecialized medicine, and as such it is not reflected in the current health insurance payment system.

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Fig. 34.3
Frailty development (Modified after: Morley [26])

In terms of diagnosis, there are on the one hand relatively complicated questionnaires evaluating a number of potential risks for an individual, with the resulting frailty index assessment (e.g. K. Rockwood’s approach), and on the other hand, there exists a substantially more simple and in terms of clinical practice more practical assessment and classification of the frailty phenotype based on syndromology (L. Fried’s approach – Fig. 34.4). Persons with a negative score are classified as “robust”. The presence of two of the above-mentioned symptoms defines the “prefrail” state of the frailty process, and the presence of three symptoms corresponds to the “frailty” state. FS prevalence in the population is estimated at 10–25 % in persons older than 65 years and at 30–45 % in those older than 85 years [26, 38, 39]. Adapted Fried’s criteria have been adopted by the American Geriatrics Society and have been recently introduced also in osteology. Similarly as in sarcopenia (sarcopenic obesity), the frailty syndrome may also pose a diagnostic problem in individuals with overweight, who are affected by the syndrome form called “fat-frail syndrome”. It is generally known that obese persons have usually better BMD values than asthenic individuals, but they are more susceptible to falls and, consequently, to fractures. The vicious “frailty cycle” starts by decreasing regular physical activity, contributing to additional physiological decrements in functional reserve capacity of multiple organ systems.
Jul 16, 2017 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Involutional Osteoporosis: Sarcopenia, Frailty Syndrome and Falls

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