UNIT 16
Alterations in Musculoskeletal
System
James A Rankin RN PhD
Associate Professor
Faculty of Nursing
University of Calgary
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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Unit 16 Table of Contents
Overview .......................................................................................................................4
Aim ............................................................................................................................. 4
Objectives .................................................................................................................. 4
Resources ................................................................................................................... 4
Orientation to Unit ................................................................................................... 5
Web Links.................................................................................................................. 5
Section 1: Osteomyelitis .............................................................................................6
Acute (Primary) Osteomyelitis Etiology............................................................... 6
Chronic (Secondary) Osteomyelitis ....................................................................... 7
Learning Activity #1—Quick Quiz ....................................................................... 8
Section 2: Osteoarthritis (Degenerative Joint Disease) ........................................9
Introduction .............................................................................................................. 9
Etiology.................................................................................................................... 12
Pathophysiology and Clinical Manifestations ................................................... 14
Learning Activity #2 .............................................................................................. 14
Management of Osteoarthritis ............................................................................. 15
Section 3: Rheumatoid Arthritis .............................................................................16
Introduction ............................................................................................................ 16
Etiology.................................................................................................................... 16
Pathophysiology and Clinical Manifestations ................................................... 17
Evaluation and Treatment .................................................................................... 17
References ...................................................................................................................19
Useful Web Site ...................................................................................................... 19
Checklist of Requirements.......................................................................................20
Bibliography ...............................................................................................................20
Answers to Learning Activities ...............................................................................21
Learning Activity #1—Quick Quiz ..................................................................... 21
Learning Activity #2 .............................................................................................. 21
Appendix A—Drugs Used in the Treatment of Rheumatoid Arthritis and
Osteoarthritis ..............................................................................................................22
Drug Therapy ......................................................................................................... 22
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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UNIT 16
Alterations in Musculoskeletal System
Patients with alterations in skeletal support/movement provide a challenge
for nurses working in a variety of settings. Problems of mobility in the
general population will have greater prominence in the near future as the
number of Canada’s elderly increases. It is important to note that not all
problems with mobility only affect the elderly. For example, osteomyelitis
can occur in both children and adults, and the same is true for rheumatoid
arthritis, whereas osteoarthritis tends to occur after the age of 40 and the
incidence increases with age.
Sound knowledge of the pathophysiology and management of the diseases
that affect mobility is important for nurses at the present time and in the not
so distant future.
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Unit 18 Alterations in Musculoskeletal System
Overview
Aim
The aim of this unit is to facilitate your understanding of the following
conditions:



acute (primary) and chronic (secondary) osteomyelitis
osteoarthritis (also known as degenerative joint disease)
rheumatoid arthritis
You are also expected to be able to describe the management of these
disorders.
Objectives
On completion of this unit you will be able to:
1. Describe the etiology, pathophysiology and management of primary
and secondary osteomyelitis.
2. Describe the etiology, pathophysiology and management of
rheumatoid and osteoarthritis.
Resources
Requirements
Read: Porth, C. M. (2005). Pathophysiology – Concepts of Altered health
States (7th ed.). Philadelphia: Lippincott. Chapter 56 for a review of the
structure and function of the MS system; Chapter 57 for trauma,
infections and neoplasms (pay attention to osteomyelitis) and Chapter 59
for rheumatic disorders. This is not as onerous as it may appear!
Print Companion: Alterations in Musculoskeletal System
Supplemental Materials
Read:
Hamerman, D. (1988). Osteoarthritis. Orthopaedic Review, 17(4), 353360.
Robson, D. (1988). Osteomyelitis: The disease, the patient and the
nurse. CONA Journal, 10(1), 4-6.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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Orientation to Unit
Prior to commencing this unit it is important that you have a basic
understanding of the musculoskeletal and immune systems and the process
of inflammation. If you require a brief review, the following readings are
recommended:
For review of the musculoskeletal system, read:



Porth - Chapter 56
or a current Anatomy and Physiology Text
Van De Graaff and Fox (1992) Ch. 9 and 10 (skim) Ch. 11 (skim)
Web Links
All web links in this unit can be accessed through the Web CT system.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 18 Alterations in Musculoskeletal System
Section 1: Osteomyelitis
Acute (Primary) Osteomyelitis Etiology
This is well documented on pp. 1380-83 in Porth. The key points are the
following:


osteomyelitis is commonly caused by a bacterial infection although
other microorganisms can cause the disease.
acute (primary) osteomyelitis can be caused in two ways:
1. Exogenous osteomyelitis (Latin, ex = “out”) the infection spreads
from outside of the body, for example, a contaminated open
fracture or gunshot wound. The infection spreads from soft tissue
to bone.
2. Hematogenous osteomyelitis (heme, hema, haem = blood) the
infection is blood borne, for example, when there is an infection in
the throat or urinary bladder, it is possible for the organism to be
carried in the blood (i.e., blood borne) and successfully invade and
infect the bone. The infection can now spread from bone to soft
tissue.
Evaluation and Treatment
The mainstay of management of both acute and chronic osteomyelitis is
surgery, long-term antibiotics and rest of the affected limb.
Surgery
This involves surgical drainage of the pus and removal of any dead bone
(sequestrectomy). In addition, metal prostheses, plates, screws and nails, if
present, are removed. There may also be intermittent or continuous closed
irrigation of the area with a solution of antibiotics.
Antibiotics
Intravenous antibiotics are used over a long period of time (6 to 8 weeks or
more) in order to achieve the continuous concentrations that are necessary for
successful treatment. This form of treatment is both time consuming and
expensive. In recent years, home care of intravenous administration of
antibiotics has been introduced. Martin (1989) has shown that oral
administration of certain antibiotics (ciprofloxacin and enoxacin) can be
effective in the treatment of osteomyelitis.
Rest
Some orthopedic surgeons may advise splinting of the affected limb to
ensure adequate rest. The limb will be splinted if the bone is unstable, a
plaster of Paris back slab may be applied or skeletal traction may be used.
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Chronic (Secondary) Osteomyelitis
Definition
Chronic osteomyelitis is said to exist when the infection is present longer
than 6-8 weeks. It generally arises from unsuccessful treatment of the acute
type. There are several factors that contribute to unsuccessful treatment.
Pathophysiology
See p.1382 in Porth.
Clinical Manifestations
Varies with:





age of individual
involved site
precipitating event
infecting microbe
stage of infection
See pp.1380 for specific signs and symptoms based on stage of infection.
Evaluation and Treatment
The treatment for the chronic condition is essentially the same as that
outlined previously. Hallmark features of the chronic condition include the
presence of dead bone (sequestrum) and new soft bone (involucrum). See p.
1382 of course text for an x-ray of hematogenous osteomyelitis of the fibula.
Sequestrum and involucrum may be seen on an X-ray. The individual with
chronic osteomyelitis experiences repeated infections with periods of
remission. There may be many years between infections. Continued removal
of dead bone may necessitate the need for bone grafting from a donor site to
the site of infection. An autograft (bone from the same person) or an allograft
(bone from the same species such as a human cadaver) may be used. If an
autograft is used, it is important that the donor site is not in proximity to the
graft site. If the sites were in close proximity there is the danger of
contamination from the graft site to the donor site. As you may appreciate
there can be much scarring both at the site of infection and on the skin
surface.
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Unit 18 Alterations in Musculoskeletal System
Learning Activity #1—Quick Quiz
(Answers in are at the end of this unit)
1. What is the name of the bacterium that usually causes hematogenous
osteomyelitis?
2. Give one example of how infection can occur by:
a. the exogenous route
b. the hematogenous route
3. Hematogenous osteomyelitis is more common in infants, children and
the elderly. Why do you think this is the case?
4. What factors make osteomyelitis difficult to treat?
5. At what point does acute osteomyelitis become a chronic condition?
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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Section 2: Osteoarthritis (Degenerative Joint
Disease)
Introduction
The generic name given to joint disease is arthropathy. The arthropathies can
be divided into two categories: non-inflammatory joint disease and
inflammatory joint disease.
The most prevalent of the non-inflammatory group is osteoarthritis or to give
it its other name, degenerative joint disease. There are approximately 3
million (or about 1 in 10) Canadians with osteoarthritis. These include:
1. Absence of synovial membrane inflammation
2. Absence of systemic clinical features
3. Normal appearance of synovial fluid
The main pathological feature of the disease is the degeneration and ultimate
loss of articular cartilage. You can see the erosion of the cartilage in figure 599 on page 1431 of the text.
Before studying the etiology of osteoarthritis, let’s take a closer look at the
structure and function of cartilage.
Function of Cartilage



Cartilage covers the end of each bone that forms a joint
It allows the bones to move smoothly (articulate) in the joint, hence it
also known as articular cartilage
Cartilage distributes the forces placed on the larger joints (hip and
knee) by our weight
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Unit 18 Alterations in Musculoskeletal System
Structure of Cartilage

Cartilage is attached to subchondral bone (sub = under; chrondral =
cartilage). See Fig. 40-10 p. 1419 of the course text. The collagen fibres
are arranged in arcades that extend up toward the surface. Figure 18.1
in this unit illustrates the section of articular cartilage that is
“magnified” in the remaining figures (Figures 20.2, 20.3, and 20.4).
Figure 18.1 Structure of articular cartilage
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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In the superficial layer the collagen fibres are arranged horizontally (see
Figure 18.2). At this point you can think of the cartilage as a springy mattress!
Figure 18.2 Collagen fibre arcades

In the spaces between the collagen fibres there are proteoglycan
molecules. These are large molecules made up of proteins,
carbohydrates and hyaluronic acid. The proteoglycans have a large
surface area and have the ability to attract water. This creates a
positive pressure inside the cartilage, (see Figure 18.3). The mattress is
now a water bed under pressure!
Note! In osteoarthritis the proteoglycan molecules are progressively
depleted.
Figure 18.3 Proteoglycans within collagen fibre spaces
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Unit 18 Alterations in Musculoskeletal System

Also found in the cartilage are cells known as chondrocytes.
Chondrocytes are like bricks that provide stability to the cartilage.
These cells continuously build up and break down the structure of the
cartilage. The chondrocytes synthesize collagen and can break it
down with enzymes such as collagenase. (See Figure 18.4 in this unit).
Figure 18.4 Chondrocytes in deep layers of cartilage
Student Activity
Review table 59-2 on page 1432 to see the characteristics of OA in
different parts of the spine.
Etiology
It used to be thought that osteoarthritis affected the large joints (hip and
knee) and was due to “wear and tear” on those joints. However, it appears
that the disease is not as simple as this. It is true that the hips and knees can
be affected, however the smaller joints of the hands, wrist and neck are more
commonly affected. It is also important to make the distinction between
primary and secondary degenerative joint disease (DJD).
Mechanical Theory
The first theory of causation that was proposed was the mechanical theory
(i.e., wear and tear), (Huskisson, 1985). It has been shown in animal studies
that walking continuously on a hard as opposed to a soft surface makes
osteoarthritis more likely, (we have to be careful about extrapolating results
from animal studies to humans). It was thought that “impact loading” caused
microscopic fractures to occur in the collagen meshwork, this in turn led to
the release of degradative enzymes which contributed to the breakdown of
the cartilage.
You can think of impact loading as something that would happen to the
articular cartilage of the ankles if a person jogged on a hard concrete surface.
The impact loading would be greater if the jogger weighed 250 pounds!
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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There are some problems with this theory as it does not explain everything
that we observe in clinical practice. For example:



How do we explain the concept of impact loading, when the joints of
the fingers and wrist are affected?
It is true that DJD increases with age. If you develop DJD in your right
knee at age 50, how do you explain the fact that the left knee may be
unaffected? Presumably the impact loading on both knees has been
similar and you can be very sure that your right knee is the same age
as your left one!
It is possible for DJD to occur quite suddenly. Whereas the concept of
wear and tear assumes that this has been going on for some years.
Biochemical Theory
The biochemical theory, as the name implies, refers to the biochemical
breakdown of cartilage by enzymes and chemicals from chondrocytes, cells
of the synovium and macrophages from the immune system. Briefly, it is
thought that there is an imbalance between the breakdown and build up of
cartilage by the chondrocytes. Moreover other enzymes may be released from
cells of the synovium and the immune system which damage and destroy the
articular cartilage.
For a more detailed explanation see p. 358 of the article by Hamerman (1988)
which is in the selected pathophysiology readings packages. (NOTE! It is
NOT necessary to read this for exam purposes.)
Thus the true etiology of primary DJD is not known. There are a number of
factors that seem to be associated with it and it may well be a combination of
factors outlined in the two theories discussed above.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 18 Alterations in Musculoskeletal System
Pathophysiology and Clinical Manifestations
Read pp. 1431-2 of course text and make brief notes.
Note:
 Loss of joint space
 Loss of cartilage.
 Sclerosis of subchondral bone
 Formation of new bone growths -- osteophytes.
 Limited range of movement
 Crepitus in the joints may be palpated and heard
 Pain in the joint, especially after walking. The distance that one can
walk varies with the severity of the disease process.
 Stiffness in the joint can occur in the morning for about 30 minutes.
Learning Activity #2
Note: The cartilage of a joint is separated from underlying bone by
a line of calcification known as the tidemark. Cartilage is not
otherwise calcified. Cartilage does not have nerves or blood vessels.
What causes the pain in osteoarthritis? (See the end of this unit for answers)
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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Management of Osteoarthritis
Briefly, the management of DJD may include:
Conservative Treatment
(See the end of this unit for a list of drugs used.)




Relief of pain by:
o using nonsteroidal antiinflammatory drugs (NSAID’s) and aspirin
o weight loss
o maintaining appropriate posture
o periods of exercise (e.g., swimming) and rest
Maintain mobility—an inactive joint becomes a stiff joint
Use a cane, crutches or walker
Local injection of steroids. This is generally not done on a long-term
basis as steroids can stimulate the activity of collagen digesting
enzymes. Also crystallization of some of the drug products can take
place in the joint, causing inflammation rather than relieving it
Surgical Treatment
Orthopedic surgery may be used to:



Realign/redirect forces on the joint (osteotomy)
Fuse a painful joint (arthrodesis)
Use prosthetic implants to:
o resurface the ends of the
o replace a joint
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 18 Alterations in Musculoskeletal System
Section 3: Rheumatoid Arthritis
Introduction
As previously stated, DJD is the most prevalent of the non-inflammatory
joint diseases. In contrast rheumatoid arthritis is the most prevalent of the
inflammatory joint diseases. The term “arthritis” simply means inflammation
of a joint. You might think that inflammation necessarily involves some
infectious agent—if you were thinking this then read the unit on the immune
system again! A joint may become infected by bacteria and cause an
infection. This would be termed infectious or septic arthritis. Rheumatoid
arthritis (RA) is an example of a noninfectious arthritis. Rheumatoid arthritis
is a chronic inflammatory disease of connective tissue. It runs a prolonged
course with exacerbations and remissions accompanied by a general systemic
disturbance. As with many autoimmune linked disorders women are more
likely to be affected than men (female to male ratio = 3:1), with about 1-3%
prevalence in the general population. Approximately 300,000 (or 1 in 100)
Canadians have RA.
There tends to be symmetrical involvement of the small or peripheral
synovial joints, such as, the hands, wrists, elbows and ankles (although any
synovial joint may be affected).
Etiology
The etiology of RA is unknown. However, as with many diseases of
unknown etiology, there have been a number of predisposing factors
identified. Fig. 41-22 on page 1467 of the course text provides you with an
overview of the pathogenesis as it relates to the immune system. Other
factors include:






Age—The average age of onset is 40, RA may occur at any age.
Sex—Female to male ratio is approximately 3:1.
Heredity—There may be a family history of RA.
Climate—It was thought that RA was more common in temperate
zones (cold and damp). However, it also occurs in other climatic
regions of the world.
Psychological factor—RA may be precipitated or aggravated by a
strong emotional disturbance.
Autoimmunity—There is strong evidence to support this. However,
it is important to note that not everyone with RA has detectable
rheumatoid factors (RF’s) in the serum. In addition, some individuals
have RF’s but do not have rheumatoid arthritis.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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Pathophysiology and Clinical Manifestations
Read pp. 1418 – 1420 of the course text and make brief notes on these
sections. Main points include:









Swelling and congestion of the synovial membrane.
Inflammatory reaction—The joints are infiltrated by plasma cells and
macrophages causing damage to the synovial membrane.
Synovial effusion—joint swelling
Hypertrophy of the synovial membrane eventually occurs
Formation of granulation tissue (pannus)
Patchy destruction of cartilage
Fibrous adhesions and pannus cause stiffening of the joints
Atrophy of the muscles adjacent to the joints
Formation of extra-articular subcutaneous modules (“rheumatoid
nodules”). These are a sign of advanced disease.
For those interested in a more detailed overview of the pathophysiology of
RA see Rankin, (1995).
Note: Remember that in contrast to osteoarthritis, RA is a systemic
disease. Other areas of the body may be affected, for example:






Vasculitis—inflammation of arterioles
Rheumatoid nodules on heart valves, in the lungs and
gastrointestinal system
Scleritis—leading to glaucoma
Sjogren’s syndrome—decrease in lacrimal and salivary gland
activity
Anemia
Felty’s syndrome—leucopenia with or without splenomegaly
Evaluation and Treatment
As the etiology of RA is unknown the treatment is symptomatic (i.e., directed
toward the relief of symptoms). The mainstay of therapy is the use of a
variety of drugs (see Appendix B for a comprehensive list). Some of these
include:






Aspirin, NSAID’s, Cox2 inhibitors
Steroids
Antimalarials (e.g., hydroxychloroquine)
Slow acting antiinflammatory agents, such as gold (e.g., sodium
thiomalate)
Chemotherapeutic agents (e.g., methotrexate)
Monocloral antibody (e.g., Remicade)
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Unit 18 Alterations in Musculoskeletal System
It is perhaps worth noting that the precise action of many of these drugs is
unknown, moreover they have potentially serious side effects.
Surgical intervention may also be helpful in the management of RA. Again, it
is to be noted that RA is a systemic disease, thus surgical intervention may
offer relief of pain and increase mobility in the operated joint (e.g., the knee).
This does not mean that the individual is cured of RA. The systemic effects of
the disease and the pain and immobility in the other joints will persist.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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References
Chenger, J. (1989). Hip hip hooray: Your total hip replacement
[Videotape]. Calgary: Calgary General Hospital.
Chenger, J. (1989). Your total knee replacement [Videotape]. Calgary:
Calgary General Hospital.
Hamerman, D. (1988). Osteoarthritis. Orthopaedic Review, 17(4), 353360.
Huskisson, E. C. (1985). Osteoarthritis: Pathogenesis and management.
Update Postgraduate Centre Series. London: The Update Group Limited.
Martin, M. E. (1989). Oral antibiotics for the treatment of patients with
chronic osteomyelitis. Orthopaedic Nursing, 8(3), 35-38.
Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health
States (7th ed.). Philadelphia: Lippincott.
Rankin, J.A. (1995). Pathophysiology of the rheumatoid joint.
Orthopaedic Nursing 14 (4) 39-46.
Robson, D. (1988). Osteomyelitis: The disease, the patient and the
nurse. CONA Journal, 10(1), 4-6.
Van De Graaff, K. M., & Fox, S. I. (1992). Concepts of human anatomy
and physiology (3rd ed.). Dubuque, IA: Wm. C. Brown Publishers.
Useful Web Site
The Arthritis Society
http://www.arthritis.ca/home.html
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 18 Alterations in Musculoskeletal System
Checklist of Requirements
 Read Print Companion: Alterations in the Musculoskeletal System
 Read Porth, Chapters 56, 57, and 59.
Bibliography
Hess, E. V., & Greenbaum, L. (1988). Adult rheumatoid arthritis: An
aggressive, early treatment plan. Modern Medicine, 56, 72-81.
Johnson, G. E., & Hannah, K. J. (1987). Pharmacology and the nursing
process (2nd ed.). Toronto: Saunders.
Kuhn, M. M. (1991). Pharmacotherapeutics: A nursing process approach
(2nd ed.). Philadelphia: F. A. Davis.
Malseed, R., & Harrigan, G. (1989). Textbook of pharmacology and
nursing care. Philadelphia: Lippincott.
Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health
States (7th ed.). Philadelphia: Lippincott.
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Unit 18 Alterations in Musculoskeletal System
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Answers to Learning Activities
Learning Activity #1—Quick Quiz
1. Staphylococcus aureus
The word aureus comes from the Latin word aurum which means
gold (e.g., Au, is the chemical symbol for gold). The bacterium is so
named because the pus that it produces is golden!
2.
a. Exogenous—open fracture, stab wound, gunshot wound,
operative procedures, venepuncture.
b. Hematogenous -- infection of the skin, gums, ear, respiratory,
gastrointestinal and genitourinary systems.
3. These groups may be more prone to infections because their immune
systems are less competent. It can be difficult for their immune
systems to deal with an infection which is superimposed on another,
(e.g., acute osteomyelitis and urinary tract infection).
4. Factors making osteomyelitis difficult to treat:
a. Small microscopic channels in bone -- allow bacteria to multiply
unimpeded.
b. Localized thrombosis of the microcirculation of the bone by
bacterial toxins.
c. Limited capacity of bone to replace itself, especially in the
presence of ongoing infection.
All of these factors make it difficult for sufficient concentrations of
antibiotic to reach the area of infection and destroy the invading
microorganism.
5. Acute to chronic
Opinions may vary, however it is generally accepted that once the
acute infection has continued for 6-8 weeks, it is said to be a chronic
osteomyelitis.
Learning Activity #2
What causes the pain in osteoarthritis?
It is not clearly understood. However, remember that bone and other soft
tissues in a joint do have a nerve supply. Therefore it is thought that
ligamentous sprain, synovitis and osteophyte formation combine to stimulate
the nerves.
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Unit 18 Alterations in Musculoskeletal System
Appendix A—Drugs Used in the Treatment of
Rheumatoid Arthritis and Osteoarthritis
Drug Therapy
The drugs used in the treatment of musculoskeletal disorders in general and
rheumatoid arthritis in particular may be categorized under the headings of:
analgesics; nonsteroidal antiinflammatory drugs (NSAID); and steroids.
1. Analgesics - NSAIDS
Acetylsalicylic Acid (Aspirin)
Used in both R.A. and O.A. One of the most common yet most valuable
drugs for the treatment of both pain, inflammation and pyrexia. Dose range
4-6g daily in divided doses. Soluble tablets are preferable.
Interactions


high doses of antacids—decrease effect of aspirin.
Anticoagulants—increased risk of bleeding,
avoid using together if possible.
Side Effects

Tinnitus, hearing loss, GI disturbance, bleeding,
vomiting.
Special
Considerations

Take with food. Do not give to patients with GI
ulcer or aspirin hypersensitivity.
When pain is
severe

Codeine phosphate 30 mg two to three times
daily may be prescribed.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
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2. Phenylbutazone (Butazolidin)
Effective NSAID in the treatment of RA. Dose -- 100 mg - 200 mg P.O. t.i.d.
Interactions



oral anticoagulants, increased risk of bleeding
oral hypoglycemics, possible to enhance
hypoglycemia
phenytoin—possible phenytoin toxicity—
monitor
Side Effects

Bone marrow depression—agranulocytosis,
thrombocyto-penia. Sodium retention, nausea,
vomiting, skin rashes
Special
Considerations

Take with food. Record weight and input and
output. If fever, sore throat or mouth ulcers
develop, stop drug
Oxyphenylbutozone and Alka Butazolidin may
be regarded as having similar properties as
phenylbutazone

3. Indomethacin (Indocid)
An effective NSAID in the treatment of RA. It belongs to the group of drugs
known as the Indole-Acetic Acids which include Tolmetin (Tolectin) and
Sulindac (Clinoril).
Dose

25 mg - 50 mg P.O. b.i.d. or t.i.d.
Interactions

Beta blockers—decreased effectiveness of beta
blockers
Side Effects


Severe gastrointestinal disturbance—bleeding.
Headache, dizziness, nausea, vomiting and
diarrhoea
Special
Considerations

Take with food. CNS side effects more
common in elderly. Use with extreme caution
in patients with history of peptic ulceration
Also available as sustained release capsules
and suppositories

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Unit 18 Alterations in Musculoskeletal System
4. Naproxen (Naprosyn)
Used in the treatment of RA and osteoarthritis. This drug is a member of the
group known as the Propionic Acid Derivatives which include Ibuprofen
(Motrin, Brufen) and Fenoprofen (Nolfon).
Dose

250-500 mg P.O. b.i.d.
Interactions

None significant.
Side Effects

Nausea, occult blood loss, gastric disturbance.
Special
Considerations

Full therapeutic effect may take up to four
weeks. Two forms of the drug are: Naproxen
and Naproxen Sodium. Both forms should not
be taken simultaneously as side effects are
cumulative.
5. Piroxicam (Feldene)
NSAID used in both R.A. and O.A.
Drug Group
Dose


the Fenamates.
20 mg P.O. once daily.
Interactions

as for Naproxen.
Side Effects

Nausea, occult blood loss, gastric disturbance.
Special
Considerations

as for Naproxen. Plus, its once a day
administration is due to longer plasma half life.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
25
6. Corticosteroids
Used as p.o. medication in the treatment of R.A., occasionally used as an
intra-articular injection in O.A.
These drugs are potent antiinflammatory agents, their adverse effects may
become severe particularly if used over a long period of time or in high
doses. Their use can be justified only if less potentially dangerous therapy is
ineffective.
Prednisone
Dose
Interactions

2.5-5 mg at bedtime is effective in relieving
morning stiffness

Anticoagulants—increase blood coagulability.
Corticosteroids increase the risk of hemorrhage
because of their effects on vascular integrity
Antidiabetic drugs—corticosteroids increase
blood glucose level.
Contraceptives—oral contraceptives containing
estrogen increase serum cortisol binding
globulin -- the rate of hydrocortisone
metabolism is therefore retarded.
Indomethacin—increased risk of GI
disturbance. Combined use is not
recommended



Special
Considerations

Take with food. Enteric coated tablets available.
Advise against abrupt withdrawal. Daily doses
taken once in the morning or twice daily dose
on alternate days.
Observe for Cushing’s Syndrome -- elevation of blood glucose, muscle
wasting, sodium and fluid retention, particularly in the face, giving rise to
“moon face” description. Redistribution of body fat, “buffalo hump,”
accumulation of fat at the lower part of the back of the neck, plethora and
hypertension.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
26
Unit 18 Alterations in Musculoskeletal System
7. Gold Products
Drugs containing gold have been shown to be very effective in the treatment
of rheumatoid arthritis. The main problem is that they have potentially very
serious side effects.
The main method of action is immunosuppression, in particular inhibition of
phagocytosis, decrease in immunoglobulins and inhibition of lysosomal
enzymes.
Gold Sodium Thiomalate (myochrysine, approximately 50% gold).
Dosage depends on individual response. Maintenance dose 50 mg I.M. q1-2
weeks x 4 to 50 mg I.M. monthly to a total dose of 0.8-10 g. Contraindicated
in renal or hepatic disease, congestive heart failure and hypertension.
Common adverse effects: dizziness, stomatitis, rashes and pruritus. Life
threatening effects: aplastic anemia, leukopenia and thrombocytopenia.
There is also an oral preparation, aurothioglucose (Solganal), this has the
same contraindications and adverse effects as the I.M. preparation.
8. Antimetabolites
In cases of severe rheumatoid arthritis a rheumatologist may prescribe an
antimetabolite such as methotrexate. Doses vary greatly from one individual
to another. Common adverse effects: nausea, vomiting, diarrhea and
stomatitis. Life threatening effects: GI hemorrhage, enteritis, and intestinal
perforation, GU tubular necrosis.
9. Cox2 inhibitors
Cox2 inhibitors are a new class of NSAID recently approved for the treatment
of various forms of arthritis. Briefly Cox2 inhibitors work as follows:







“Cox” is an acronym for the enzyme cyclo-oxygenase. There are two
isoforms of the enzyme designated Cox1 and Cox2.
Cox enzymes are integral to prostaglandin (PG) production.
Cox1 enzymes help to produce PGs that are protective to the gut.
Cox 2 enzymes produce PGs associated with pain and inflammation
in rheumatoid arthritis.
The current NSAIDs and ASA inhibit Cox1 and Cox2. This means that
these NSAIDs and ASA reduce the pain and inflammation of RA but
there is also a loss of protection to the gut (which can cause GI upset
and bleeding).
Cox2 inhibitors selectively inhibit Cox2 resulting in a reduction in
pain and inflammaiton and protection for the gut.
Cox2 inhibitors currently on the market are: Celebrex (Searle). Vioxx,
as you know, was removed from the market last year due to
cardiovascular concerns.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 18 Alterations in Musculoskeletal System
27
10. Monocloral Antibody
On November 11, 1999 the FDA in the United States approved Inflizimab
(Remicade) to be used for the treatment of RA in conjunction with
methotrexate. Remicade has limited availability in Canada at the present
time. Briefly Remicade acts as follows:



Tumour necrosis factor  is a principal mediator of inflammation in
RA.
Remicade is a monoclonal antibody which reduces the level of
tumour necrosis fact  on cell membranes and in the blood.
It is administered intravenously.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary