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Chapter 6
The Skeletal System and Drug
Therapy
© Paradigm Publishing, Inc.
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Chapter 6
Topics
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Anatomy and Physiology of Bones and Joints
Osteoporosis
Arthritis
Herbal and Alternative Therapy
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Anatomy and Physiology of Bones and Joints
Bones
• Provide structure and support for the body
• Provide movement along with muscle and protect organs
• Long bones, such as the femur, contain marrow, the
birthplace for blood cells
• All bones store calcium and maintain its balance
 Osteoclasts break down bone tissue, releasing calcium
 Osteoblasts take calcium from blood and build bone
• Grow and increase in density at the greatest rate during
childhood and continue to build into the 30s
 Bone density gradually decreases over time
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Anatomy and Physiology of Bones and Joints
Anatomy
of the
Skeletal
System
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Anatomy and Physiology of Bones and Joints
Microscopic
View of Bone
Osteoclasts and
osteoblasts
provide bone
homeostasis, a
continual process
that grows and
repairs bone
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Anatomy and Physiology of Bones and Joints
Anatomy of a
Joint
(Articulation)
The ends of
bones are coated
with cartilage
and cushioned
from friction by
the synovial
membrane and
synovial fluid
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Osteoporosis
Facts about Osteoporosis
• Is a reduction in bone density, resulting in weakened bones
and fractures
• Occurs when bone density decline accelerates abnormally
• Causes fractures in the hips, spine, and wrists
 Hip fractures can be life threatening for older patients
• 90% of patients with osteoporosis are women
• Risk Factors: female, Caucasian, family history, small body
frame, smoking, heavy caffeine intake, low calcium intake
• Estrogen promotes bone density and estrogen levels
decreases after menopause
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Osteoporosis
Screening Tests for Osteoporosis
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Many pharmacies provide screening tests
BMD machines use x-ray and ultrasound
Usually measure the heel; good estimate of hip and spine
Pharmacists and technicians can be trained to perform test
Result of BMD provides a T-score which is estimate of risk
If at risk, patients can make lifestyle changes
 Add weight-bearing exercise, eat foods high in calcium,
quit smoking, and decrease caffeine intake
• Diagnosis of osteoporosis may require drug therapy
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Osteoporosis
Drugs for Osteoporosis: Calcium
• Healthy adults should get 1,000 mg of calcium a day
• Patients with osteoporosis, people over 65, and women
after menopause should get 1,500 mg of calcium a day
• Daily calcium total obtained through diet and dietary
supplements
• Calcium dietary supplements
 Various products
 Routes: oral; several dosage forms
 Dose: divided doses; only 500–600 mg of calcium
is absorbed at a time
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Osteoporosis
Drugs for Osteoporosis: Calcium (continued)
 Side Effects (common): nausea, vomiting, and
constipation
 Side Effect (severe): excess calcium can cause kidney
stones
 Caution: do not take if kidney stone history
 Caution: do not take with quinolone antibiotics,
tetracyclines, or iron supplements
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Osteoporosis
Drugs for Osteoporosis: Vitamin D
• Improves calcium absorption in the GI tract and helps
other osteoporosis agents work more effectively
• In fish, milk, breakfast cereals, and exposure to sunlight
• Often is a combination product with calcium
• Recommended daily requirements are 400 IU but many
physicians prescribe up to 1,100 IU a day
• Indications: osteoporosis and osteopenia (high risk for
developing osteoporosis)
• Side Effects: nausea, vomiting, and edema (swelling)
• Cautions: hypercalcemia and kidney problems
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Osteoporosis
Drugs for Osteoporosis: Bisphosphonates
• Mechanism of Action: inhibit osteoclasts from removing
calcium from bone tissue; prevent bone breakdown
• Indications: mainly osteoporosis, Paget’s disease, and
some bone and spinal injury cases
• Dosage Forms: variety of oral and infusion choices
• Side Effects: headache, nausea, vomiting, diarrhea,
constipation, abdominal pain, and indigestion
• Side Effects (severe, rare): insomnia, anemia, osteonecrosis
• Cautions: If oral, take on an empty stomach with water
• Storage for IV: refrigerate and then use within 24 hours
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Osteoporosis
Drugs for Osteoporosis: SERMs
• Available SERMs: Raloxifene (Evista), tamoxifen (Nolvadex),
and toremifene (Fareston)
• Mechanism of Action: work as estrogen receptors that
mimic the effects of estrogen on bone mineral density
 Do not increase risk of breast or uterine cancer
• Side Effects of Raloxifene: hot flashes, headache, diarrhea,
joint pain, leg cramps, and flulike symptoms
 Side Effects (severe): deep vein thrombosis or blood
clots
 Cautions: Do not take if prolonged immobility
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Osteoporosis
Drugs for Osteoporosis: Human Parathyroid
Hormone
• Teriparatide (Forteo) is a human parathyroid hormone
• Mechanism of Action: supplements the body’s production
of parathyroid hormone
 Regulates the calcium–phosphate balance and
stimulates new bone growth
• Indication: very severe osteoporosis; used short-term
• Cautions: associated with osteosarcoma; do not take if
have Paget’s or risk for bone cancer
• Patients taught how to use injector; drug kept refrigerated
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Your Turn
Question 1: What is a restriction of raloxifene, a SERM used for
osteoporosis?
Answer: Raloxifene should not be taken if prolonged
immobility is anticipated.
Question 2: What is the purpose of taking vitamin D with
calcium?
Answer: Vitamin D improves calcium absorption from the GI
tract. It also helps other osteoporosis agents work more
effectively.
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Arthritis
Arthritis and Osteoarthritis (OA)
• Arthritis
 Is the most common joint disorder and it affects
millions
• OA
 Is the most common type of arthritis
 Caused by wear and tear on joints that comes with age;
onset is usually after age 40 or 50
Joint cartilage erodes and causes painful rubbing
 Large joints such as knees, shoulder, and hips affected
first
 Symmetry often not present
 Morning stiffness is prominent but is relieved by
activity
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Arthritis
Rheumatoid Arthritis (RA)
• Is an abnormal process in the immune system that
destroys the synovial membrane and produces
inflammation in the joint
• Small joints (fingers, wrists, and elbows) affected first
• Symmetry often present
• Deformation of the joints can be disabling
• Morning stiffness and pain are not relieved
after an hour or by activity
• Two lab tests to help diagnose are ESR and RF
• Disease is not curable but can be slowed with drug therapy
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Arthritis
Gouty Arthritis (Gout)
• Is a condition in which excessive uric acid accumulates in
the blood and urate crystals then form in the synovial fluid
and irritate joints
• Joint pain and swelling often first occur in the big toe
 Can cause kidney damage without drug therapy
• Drugs that predispose someone to gout are diuretics,
salicylates, nicotinic acid (niacin), ethanol, cytotoxic agents
• Certain foods rich in purine (amino acid), like red meat,
also implicated in gout
• Chronic preventive therapy may be prescribed
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Arthritis
Drugs for OA
• Reduce pain and inflammation but do not cure
 Severe OA may require surgery or joint replacement
• Other remedies include physical therapy, cold/hot packs
massage, and rest
Drugs for OA: Acetaminophen
• First-line choice that controls pain, not inflammation
 Route: oral, taken multiple times a day
Drugs for OA: NSAIDs
• Mechanism of Action: inhibit enzymes COX-1 and COX-2
from producing prostaglandins
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Arthritis
Drugs for OA: NSAIDs (continued)
• Are good when inflammation is the main cause of pain or
acetaminophen no longer works
• Indications: mild to moderate pain, including arthritis
• Side Effects: headache, diarrhea, nausea,
constipation, and occasional dizziness and drowsiness
• Side Effects of GI Tract: indigestion, heartburn, abdominal
pain, bleeding, ulcer, or anemia (from blood loss)
• Routes: all oral; some not chewed or crushed
• Cautions: renal (kidney) problems, fluid accumulation,
drug interactions; do not take with aspirin
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Arthritis
Pain Pathway
• Prostaglandins
 promote
inflammation
and connect to
pain receptors
to trigger the
pain response
 Protect the GI
lining against
erosion from
gastric acid
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Arthritis
Drugs for OA: COX-2 Inhibitors
• Celecoxib (Celebrex) is the only COX-2 inhibitor available
• Mechanism of Action: inhibits COX-2 from production of
prostaglandins that cause pain and inflammation
 Does not inhibit COX-1 from protecting GI lining
• Indications: arthritis pain; pain with ulcers or GI bleeding
• Side Effects: headache, abdominal pain, heartburn,
nausea, and occasional GI irritation and bleeding
• Routes: oral; can be taken short- or long-term
• Cautions: monitor heart function
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Your Turn
Question 1: A patient is diagnosed with mild OA. What is the
physician likely to order?
Answer: The drug of choice for OA is acetaminophen.
Question 2: How is the function of a COX-2 inhibitor different
than the function of a NSAID?
Answer: A COX-2 inhibitor blocks COX-2, an enzyme that
promotes the production of the prostaglandins that cause
pain and inflammation. NSAIDs block both COX-1 and COX-2,
which cuts off prostaglandins that protect the lining of the
GI tract.
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Arthritis
Drugs for RA
• Goal of drug therapy is to maintain mobility and delay
disability for as long as possible
• Can improve pain and slow the disease progression
Drugs for RA: DMARDs
• Indications: slow disease progression of RA and used as
immunosuppressants used after organ transplant
• Mechanism of Action: inhibit immune system to slow
down destruction of joint tissue
• Best started within first 3 months from diagnosis; taken on
chronic basis to maintain disease and symptom control
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Arthritis
Drugs for RA: DMARDs (continued)
• Disease remission can sometimes be achieved
• Early therapy slows joint destruction
• Side Effects: vary among agents; effects can mimic those
of chemotherapy and are unpleasant
• Routes: oral (some not chewed or crushed), IM, IV, and SC
• Cautions: increased incidence of infection; avoid people
who are ill and use other precautions to prevent infection
• Cautions: many cause kidney damage
• Preparation and Storage: some DMARDs have special
mixing and storage; refrigerate injectable forms
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Arthritis
Drugs for Gouty Arthritis
• Treatment during an acute gout attack differs from
prevention of gout attacks
• Indications (chronic, low-dose therapy): a very severe
attack or repeated gout exacerbations within a year
• Mechanism of Action: lower uric acid levels in blood and
reduce inflammation within joints caused by urate crystals
• Colchicine is drug of choice to lower uric acid in acute and
chronic attacks; used in preventive therapy at a lower dose
• Triamcinolone Injection is a corticosteroid administered
directly into the joint for gout attack
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Arthritis
Drugs for Gouty Arthritis (continued)
• Allopurinol is the most frequently prescribed drug for gout
prophylaxis
• Side Effects (common): vary among agents; includes
diarrhea, nausea, rash, vomiting, and headache
• Routes: all are oral except triamcinolone
• Administration of Triamcinolone: intra-articular (injected
directly into the joint) to relieve pain and inflammation
• Cautions for Probenecid: drink plenty of water
(can harm the kidneys); do not take with aspirin
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Herbal and Alternative Therapies
• Glucosamine
 Taken to improve pain and stiffness from OA
 Studies do not support that it is effective
 Side Effects: nausea, heartburn, diarrhea, and
constipation
 Caution: do not take if allergic to shellfish
• Chondroitin
 Taken with glucosamine for hip and knee OA
 Studies do not support that it is effective
 Side Effects: nausea, heartburn, diarrhea, constipation
 Side Effects (rare): eyelid swelling, lower limb swelling,
hair loss, and allergic reaction
© Paradigm Publishing, Inc.
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Summary
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Bisphosphonates and SERMs used to treat osteoporosis
Calcium and vitamin D are taken for osteoporosis
Acetaminophen is the first-line choice of therapy for OA
Many patients with OA progress to long-term NSAIDs
DMARDs halt progression of RA, and NSAIDs are used to
treat pain
• DMARDs have many side effects and are difficult to take
• Drugs such as colchicine and allopurinol are used for gout
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