MUSCULOSKELETAL SYSTEM

Loss of bone and muscle with advancing age represent a huge threat to loss of
independence in later life.
Osteoporosis represents a major public health problem through its association
with fragility fractures.

Sarcopenia, the age related loss of muscle mass and function, may add to
fracture risk by increasing falls risk.
In the context of muscle aging, it is important to remember that it is not just a
decline in muscle mass which contributes to the deterioration of muscle
function.
Other factors underpinning muscle quality come into play, including muscle
composition, aerobic capacity and metabolism, fatty infiltration, insulin
resistance, fibrosis and neural activation.

Genetic, developmental, endocrine and lifestyle factors, such as physical

activity, smoking and poor diet have dual effects on both muscle and bone
mass in later life.
Recent work has highlighted a possible role for the early environment. 1

Movement related problems are commonly linked to the ageing process, so it

comes as no surprise to find that significant changes in the musculoskeletal
system occur with ageing.

Hamerman (1997) lists several implications of age related changes in the

musculoskeletal system:
physical and social impacts from pain;
health costs associated with diagnosis and treatment, especially of fractures
related to osteoporosis;
costs associated with dealing with the disability caused by arthritis.
He states that musculoskeletal degeneration is overlooked in the planning and
provision of health services, despite its importance.

1Curtis E; Litwic A; Cooper C; Dennison E. Determinants of Muscle and Bone Aging. Journal of Cellular
Physiology. 230(11):2618-25, 2015
 Remember that the key focus of aged care is on the maintenance of function.
Musculoskeletal disorders that limit mobility have a significant adverse effect on
function.

The main age-related changes in the musculoskeletal system are loss of muscle
mass, loss of mineral density & osteoarthritis.

1. THE MUSCULAR SYSTEM

Normal physiological age-related changes in skeletal muscle

Our muscle strength peaks somewhere between 20 and 30 years of age.

It then steadily decreases.
There are two factors which contribute to this strength loss.
The first is the loss of contractile tissue.
The amount of contractile tissue determines the tension (=the state of being
stretched tight) that can be developed during a muscle contraction, and the
ability to develop tension equates with strength.
The second factor is that the aged tend to do less heavy physical work, so their
muscles lose strength.
In fact, the two may be interrelated.

Loss of strength Loss of interest in exercise

The decrease in contractile tissue is part of an overall decline in muscle mass.

After the age of 30, the number and size of muscle fibres progressively
decreases, resulting in a decrease in skeletal muscle mass (from about 43% to
25% of lean body mass).
The skeletal muscle tissue is replaced by fat or fibrous tissue, neither of which
has contractile (=able to contract) properties, and cannot develop tension.
These age-related changes are particularly pronounced in the lower limbs.
 An age-associated loss of muscle mass and strength--sarcopenia--begins
at around the fifth decade of life, with mass being lost at ~0.5-1.2% per
year and strength at ~3% per year.
Sarcopenia can contribute to a variety of negative health outcomes,
including an increased risk for falls and fractures, the development of
metabolic diseases like type 2 diabetes mellitus, and increase the chance
of requiring assisted living.

Linear sarcopenic declines in muscle mass and strength are, however,

punctuated (=interrupt something at intervals) by transient periods of
muscle disuse that can accelerate losses of muscle and strength, which
could result in increased risk for the aforementioned conditions.

Muscle disuse is recognizable with bed rest or immobilization (for

example, due to surgery or acute illness requiring hospitalization);
however, recent work has shown that even a relative reduction in
ambulation (reduced daily steps) results in significant reductions in muscle
mass, strength and possibly an increase in disease risk.

Although reduced ambulation is a seemingly "benign" form of disuse,

compared to bed rest and immobilization, reports have documented that
2-3 weeks of reduced daily steps may induce: negative changes in body
composition, reductions in muscle strength and quality, anabolic
resistance, and decrements in glycemic control in older adults.
Importantly, periods of reduced ambulation likely occur fairly frequently
and appear more difficult to fully recover from, in older adults. 2

The "use it or lose it" rule applies to muscle strength in the aged.

The end result of these changes may be the development of sarcopaenia (which
literally means a deficiency of flesh).

2
Bell KE; von Allmen MT; Devries MC; Phillips SM. Muscle Disuse as a Pivotal Problem in Sarcopenia-related Muscle Loss and
Dysfunction. The Journal of Frailty & Aging. 5(1):33-41, 2016.
Sarcopenia is a loss of skeletal muscle mass in the elderly that is an
independent risk factor for falls, disability, postoperative complications, and
mortality.
Although its cause is not completely understood, sarcopenia generally results
from a complex bone-muscle interaction in the setting of chronic disease and
aging.
Sarcopenia cannot be diagnosed by muscle mass alone.

Diagnosis requires 2 of the following 3 criteria: low skeletal muscle mass,

inadequate muscle strength, and inadequate physical performance.
Forty-four percent of elderly patients undergoing orthopedic surgery and 24%
of all patients 65 to 70 years old are sarcopenic.
Although dual-energy x-ray absorptiometry and bioelectrical impedance analysis
may be used to measure sarcopenia and are relatively inexpensive and
accessible, they are generally considered less specific for sarcopenia compared
with computed tomography and magnetic resonance imaging.3

Age-related factors contributing to sarcopaenia include:

reduced levels of exercise and physical activity;
a loss of muscle motor units, particularly fast twitch fibres (which are
responsible for explosive muscle contractions); and
reduced skeletal muscle protein synthesis.

A motor unit is a group of muscle fibres innovated by a single motor nerve.

The fact that we lose motor units as we age suggests that changes in the
nervous system contribute to changes in the muscles.
With ageing, there is a decrease in the number of motor nerves supplying the
muscle and in the background activity in these nerves.
The background activity is important because if it is decreased there will be a
loss of muscle fibres mass.

Effects of ageing on the nervous system may contribute to the loss of muscle
strength.

3 Bokshan SL; DePasse JM; Daniels AH. Sarcopenia in Orthopedic Surgery. Orthopedics. 39(2):e295-300, 2016
Endocrine changes that cause a relative deficiency of anabolic hormones, such
as growth hormone (GH) and testosterone might also contribute to the loss of
muscle strength.

Endocrine changes may contribute to the loss of muscle strength.

Malnutrition will result in the loss of muscle mass.

A vicious cycle develops because a reduction in muscle mass causes a reduction
in appetite which exacerbates nutritional problems.
Elderly patients with sarcopaenia and insufficient dietary protein require
nutritional support.

Poor nutrition may contribute to sarcopaenia.

The reduction in muscle mass and the relative increase in the proportion of
slow twitch muscle fibres contribute to a slower walking speed, which may
have implications for daily activities such as crossing a road.
It is good to have an idea of what a healthy older person can normally do.
They can usually
easily climb stairs,
rise from a squatting position,
walk along a straight line,
hop on either foot, and
perform typical activities of daily living.

However, elderly people whose mobility is restricted, particularly those with

acute illness or who are bedridden, lose muscle mass and strength as the result
of deconditioning.
The rate of loss is greatest in the antigravity muscles - those used to sit up,
stand up, and pull up - which are essential for performing activities of daily
living.

Hospitalised elderly people, especially those who are bedridden, require early
and individualised exercise regimens (=a set of rules about food and exercise or
medical treatment that you follow in order to stay healthy or to improve your
health).
For 1 day of absolute bed rest, up to 2 wk of reconditioning may be necessary to
return to baseline function.
Exercises which focus on improving core body strength have been shown to be
most helpful in all elderly people in restoring and maintaining muscle strength
and preventing falls.

Bed rest is dangerous for older people.

Hospitals can be dangerous places for older people.
The rate at which strength is lost in hospitals is phenomenal.

But there is good news.

Appropriate exercise programs can prevent loss of strength or reversed after it
has occurred.

Because decreased exercise is a cause of decreased muscle strength in the aged,

exercise programmes can help maintain strength, or restore strength that has
been lost.

The role of the muscle is not limited to movement.

Muscle is involved in:
thermoregulation
- the contractile activity of the muscles generates heat (think of the effects of
shivering): people with sarcopaenia may have impaired thermoregulation;
glucose regulation
- sarcopaenia may contribute to the development of type II diabetes as the
muscles are a major site of glucose uptake (=the process by which something
is taken into a body or system) and storage;

drug storage
- a decrease in muscle mass may increase the effective circulating
concentration of drug, increasing the risk of adverse reactions;
regulation of nutrient intake
- loss of muscle mass may cause a decrease in food intake which in turn may
cause nutritional deficiencies.

2. THE SKELETON
Normal physiological changes in the ageing bone

The most important age related change in the bone is the loss of mineral, which
results in loss of strength.
This is osteoporosis.
Osteoporosis is a disease in which bone mass is reduced.
The bone that is present is generally normal, although some changes to its
micro architecture occur.
Its not specifically diseased-it is best to imagine that there is just less bone than
usual.
The loss of bone mass causes a loss of bone strength, which increases the risk
of fracture.

Osteoporosis is due to an imbalance between reabsorption and replacement of

bone.
Bone strength in later life is determined by 2 factors: peak strength of bone
achieved in early adulthood and subsequent age-related & hormone deficiency-
related bone loss.
The peak bone mass is determined by a huge variety factors, with a significant
influence from the amount of exercise done in early life, and the calcium intake
in the diet.
These factors continue to be significant in slowing the rate of mineral loss that
occurs with ageing.

Adolescence is a critical period for bone health because the amount of bone
mineral gained during this period typically equals the amount lost throughout
the remainder of adult life.
Peak bone mass is reached in the thirties, and declines from then.
After 4050 years of age, bone loss may progress slowly in both sexes, with a
period of more rapid loss in women during the menopause accounting for bone
loss of 1220% over a period of 5 years.
Thereafter, age-related bone loss is modest (0.6% per year), but because of long
life expectancy, both sexes may lose a total of 40% of bone over their lifetime. 4

4 Edwards BJ, Li J (2013). Endocrinology of menopause. Periodontology 2000, 61:177194.

Bone loss that occurs as part of normal aging can be divided into 2 types:
Type 1 which is characterised by a rapid loss of bone mineral, rapid one that
affects women after menopause (postmenopausal bone loss)
and Type 2 that affects both women and men after age 60 to 70, and which is
associated with much slower bone loss (senescent bone loss).

Sarcopaenia, inadequate calcium in the diet, insufficient exposure to sunlight or

fresh foods, and reduced mechanical loading (e.g. weight bearing exercise) also
contribute.
Inactivity due to pain from fractures can also be important, and means that
problem becomes self perpetuating:
decreased exercise decreased bone mass fracture pain decreased
exercise.

Menopausal bone loss:

Before menopause, sex hormones protect the bone, at least in part, by
regulating and maintaining the balance between continual bone resorption
(by osteoclasts - the bone reabsorbing cells) and continual bone formation
and remodelling (by osteoblasts - the bone producing cells).
Oestrogen suppresses osteoclasts and declines sharply at menopause,
causing rapid bone loss during the next 5 to 10 yrs.
The sudden loss of sex hormones can increase the rate of bone loss up to 10-
fold.
In men, testosterone production normally declines gradually, so bone loss is
linear and slow.
However, in men who undergo castration as a treatment for prostate cancer,
the abrupt cessation of testosterone production results in rapid bone loss.

Senescent bone loss:

The amount of bone formed during remodelling decreases with age in both
sexes, causing a consistent decrease in bone wall thickness.
Vitamin D is thought to play a role in inhibiting the death of osteoblasts;
vitamin D deficiency may result in a decrease in the number of osteoblasts
and consequently contribute to the age-related decrease in bone formation.
Apart from the loss of mineral caused by increased osteoclast activity, the
second important reason for the loss of bone strength in the elderly is a
decrease in protein synthesis, which results in decreased collagen deposition.
Because collagen provides the framework around which bone is built, decreased
collagen levels will result in smaller amounts of normal bone.

There is increased destruction and decreased replacement of bone with ageing.

Pathologic factors may also contribute to the loss of bone mass in either sex.
Pathological fractures occur as a result of disease-related damage to the bone
that decreases its strength.
That means that pathological fractures can occur when very small forces are
applied to the bone.
The risk factors include high circulating levels of glucocorticoids and thyroxine,
alcoholism, prolonged immobilization, gastrectomy, malabsorption, renal
disease (hypercalciuria), some types of cancer, and cigarette smoking.

Lifestyle and disease factors increase the risk of pathological fractures.

What the age-related changes mean

The World Health Organisation defines osteoporosis as having a bone mineral

density more than 2.5 standard deviations (SD) below the young normal mean.
Osteopenia is defined as having a bone mineral density more than 1 SD but less
than 2.5 SD below the young normal mean.
Because women accumulate less skeletal mass than men during their growing
years (particularly during puberty), resulting in smaller, narrower, more fragile
bones, and because women undergo menopausal bone loss, women are at
higher risk for osteoporosis.

Fractures occur commonly at the proximal ends of long bones (e.g. head of
femur) and the spine, often with minimal trauma.
The effects of these fractures may range from the obvious to more subtle signs
such as chronic pain and hunching (=bend the top part of your body forward
and raise your shoulders and back) of the shoulders, which limits the capacity of
the lungs.
In Western societies approximately 40% of women and 13% of men will
experience a hip, spine or wrist fracture.
In women, wrist fractures commonly occur during the sixth decade of life,
vertebral fractures occur during the seventh decade and hip fractures occur
during the eighth decade of life.
In men, osteoporotic fractures occur at a more advanced age.

It is critical to recognise that most cases of osteoporosis go undiagnosed.

In the United States, routine screening for osteoporosis is recommended for
women who have reach the age of 65, and men who have reach the age of 70.
The consequences of osteoporotic fractures appear to be more severe in men
than they are in women.

The most commonly used form of prevention of osteoporotic fracture is

Hormone Replacement Therapy (HRT).
It has been shown that the use of oestrogens for 5 yrs is associated with a 50%
reduction in the risk of hip fracture and vertebral fracture.
The balance between risk and benefit of HRT is debated.
Several years ago it was widely believed that HRT result of a significantly
increased risk of various cancers, and therefore it is recommended that women
should not use HRT for more than five years.
However more recent research has suggested that HRT is not associated with
cancer, and in some European countries women are prescribed HRT indefinitely.
That is not the case in Australia-the five-year limitation still applies.

Bisphosphonates are the recommended first line specific treatment for

osteoporosis (HRT can be considered a non-specific treatment as it has diverse
effects).
They are prescribed to people who have osteoporosis diagnosed on the basis of
DEXA scans, and also to people who have suffered fractures, even though their
bone mineral density does not reach the threshold for a clinical diagnosis of
disease.
Bisphosphonates decrease the reabsorption of bone by decreasing osteoclast
numbers.
They also increase the overall quality of bone, so the risk of fracture is
decreased to a much greater extent than can be accounted for by the change in
bone mineral density.

Bisphosphonates have been associated with a number of adverse effects.

However, these side-effects are quite rare, and overall the benefits of
bisphosphonates are believed to considerably outweigh the risks.
There is no doubt that fractures associated with osteoporosis are associated
with enormous morbidity and mortality.
However, the media have focused on the rare adverse events and this has led
some people to question whether they should be used.
The focus on risks, rather than the risk: benefit ratio has important health
consequences for many diseases: consequences that can be attributed to
journalism focused on sensationalising (=exaggerate a story so that it seems
more exciting or shocking than it really is) stories.

One approach to decreasing the risk of adverse events is the use of drug
holidays after 3 to 5 years of bisphosphonate treatment.
Because bisphosphonates are stored in the bone there anti-reabsorbed if
effects continue after their use has stopped.
It appears that this effect may last for up to one year.

Exercise improves muscle mass, reducing fracture risk during a fall.

Regular weight-bearing exercise produces a small benefit to bone density in
postmenopausal women, although it is unable to prevent postmenopausal bone
loss.

Adequate vitamin D levels and dietary calcium intake are needed for effective
primary fracture prevention with greatest benefits occurring in the elderly with
vitamin D deficiency and/or low dietary calcium intakes.
For secondary fracture prevention, i.e. preventing further fractures in the
elderly who have already sustained a fragility fracture, specific anti-osteoporosis
treatment is necessary.
However, to maximise the benefits of these medications, vitamin D deficiency
should be corrected and adequate dietary calcium consumed. 5
5Winzenberg T. van der Mei I. Mason RS. Nowson C. Jones G. (2012) Vitamin D and the musculoskeletal
health of older adults. Australian Family Physician. 41(3):92-9
Vitamin D supplementation (=the act of adding something to something else in
order to improve or complete it) above normal requirements has not shown any
benefit in the treatment or prevention of osteoporosis.

Although vitamin D does not appear to have the expected effect on the
skeleton, it does seem to have many other benefits for aged people.
Vitamin D supplementation can prevent falls, particularly in the vitamin D
deficient elderly.

It has generally been believed that vitamin D deficiency is rare in Australia.

Statins

Statins are used to treat patients with acute coronary syndromes or established
cardiovascular disease, diabetes mellitus, chronic renal disease-all common
conditions affecting the aged.
Statins decrease cholesterol concentrations in the blood, and improve lipid
profiles, reducing the risk of cardiovascular disease.

However, myopathy is a common complication of statin use.

This shows that drugs used to treat one condition may contribute to the
development of others.
This concept will be reviewed in more detail in the module on pharmacology.
The myopathy results in reduced force production, which may in turn
contribute to decreased exercise capacity and an increased risk of falls.
Statins exert their effect by decreasing protein synthesis in muscle cells, and
also by changing the metabolic pathways responsible for energy production. 6
They also reduce the ability of muscles to repair after injury has occurred.

Describe how musculoskeletal reserve capacity changes with age and explain
the factors that contribute to this change.
What are the similarities between the answer to this question and causes of
changes in reserve capacity in other body systems?

6 Camerino GM. Pellegrino MA. Brocca L. Digennaro C. Camerino DC. Pierno S. Bottinelli R. (2011) Statin or
fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle.Biochemical Pharmacology.
81(8):1054-64.
 As predicted ageing results in a decrease in reserve capacity in the
musculoskeletal system.
This is due to changes in the muscle and the that are a normal part of ageing,
and can be exacerbated disease affecting different systems.
There is also a decrease in muscle mass and also bone strength.
As has been observed previously in other systems, these changes can be direct
(occurring specifically in the musculoskeletal system), or can be compensated
changes occurring as a result of changes in other parts of the body.

How do changes in other body systems affect musculoskeletal function in the

aged?
Changes in the cardiovascular and respiratory system that limit exercise
capacity result in a loss of muscle mass and strength.
Changes in the immune system that result in increased inflammation results in a
loss of muscle mass.
Changes in the nervous system result in a loss of muscle mass, as will changes in
the endocrine system.
The same changes may cause a decrease in bone strength.
Diseases in the endocrine, gastrointestinal and renal systems can result in a loss
of bone mass, as can medications and lifestyle choices.

You should return to your concept map, and try to integrate changes in
musculoskeletal function with some of the more general changes that are
observed in an aged person.

Decreased muscle strength leads to decreased exercise capacity and loss of

fitness.
Decreased muscle strength may increase the risk of falling, and decreased bone
strength increases the risk that fractures will result from falls.
Fractures result in hospitalisation, which results in a further loss of muscle and
bone strength.
Micro fractures in the vertebrae result in postural changes that increase the risk
of falling.

Decreased exercise capacity leads to a loss of appetite.

A loss of appetite leads to further losses in muscle and bone strength resulting in
further decreases in exercise capacity.
Changes in muscle and bone that reduce mobility may also contribute to
depression with a resulting loss of appetite and insomnia.
These may also increase the risk of falls.

A loss of muscle mass can result in changes in drug storage in the body.
This increases the risk of adverse events related to drugs.
Common adverse events include falls, depression, insomnia, loss of appetite, and
cognitive decline.