This document provides an overview of musculoskeletal and soft tissue disorders including definitions, epidemiology, clinical findings, and treatment strategies for various conditions. Key points discussed include osteogenesis imperfecta, achondroplasia, osteopetrosis, osteoporosis, Paget's disease, osteomyelitis, neoplastic bone disorders, joint disorders, synovial fluid analysis, classification of joint diseases, signs and symptoms of joint diseases, and osteoarthritis.

1. WELCOME TO
Course Title Pharmacology
Topic Name :musculoskeletal and soft
tissue disorder
By Ms. Fouzia karim
Pharm D, M phil
Hajvery University (HU)

2. Learning Outcomes :
• Etiology of hypertension
• Mechanism
• Treatment strategies
• Hypertensive emergency

3. musculoskeletal
• Bone disorder
A. Osteogenesis imperfecta (brittle bone disease)
1. Definition: Inherited generalized disorder of connective tissue characterized by defective
synthesis of type I collagen
2. Epidemiology
a. MC type is autosomal dominant (AD) disease
b. Increase in perinatal death. Families with severe postmenopausal osteoporosis should be
evaluated for possible osteogenesis imperfecta.
3. Clinical findings
a. Pathologic fractures occur at birth with minimal trauma (Link 24-1).
b. Patients have blue sclera. Reflection of the underlying choroidal
veins through the thin sclera. Sclera is thin because of the lack of type I
collagen.
c. Presenile deafness occurs in patients in their 20s and 30s.
d. Other findings: short stature, scoliosis, brittle teeth, short limbs

4. Achondroplasia
• Definition: Hereditary condition associated with impaired proliferation of
cartilage at the
growth plate; results in very short limbs and sometimes a face that is small
in relation to the
(normal-sized) skull
2. Epidemiology
a. AD disease
b. Mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Gene
mutations
increase with paternal age.
3. Clinical and laboratory findings (Fig. 24-1 B; Link 24-2)
a. Macrocephaly, depressed nasal bridge
b. Shortened arms and legs, redundant skin folds in arms and legs
c. Normal serum growth hormone (GH) and insulin-like growth factor 1
(IGF-1) levels

5. Osteopetrosis (marble bone disease
• Definition: Rare inherited disease caused by a failure of the osteoclasts to
reabsorb bone; net result is the formation of dense but disorganized bone,
resulting in bone fractures
2. Epidemiology
a. The three distinct clinical forms of the disease are infantile (autosomal
recessive [AR]),
intermediate (AR), and adult onset (AD).
b. Adult form has a good prognosis; the other types have a poor prognosis.
c. Overgrowth and sclerosis of the cortical bone (“too much bone”)
3. Clinical findings
a. Pathologic fractures
b. Anemia caused by replacement of marrow cavity by bone
c. Cranial nerve compression causing visual and hearing loss

6. Osteoporosis
• Definition: The progressive loss of both organic bone matrix (osteoid) and mineralized
bone
Epidemiology
a. MC metabolic abnormality of bone
b. Risk factors
(1) Family history of osteoporosis; currently smoking cigarettes
(2) Thin body habitus; current use of corticosteroids (MC secondary cause)
(3) Sedentary life tyle, premature menopause, heavy alcohol intake
c. Bone mass peaks at age 30 years and is slightly greater in men than women.
d. During the fourth and fifth decades of life, both sexes start losing bone.
e. Loss of both organic bone matrix (osteoid) and mineralized bone produces decreased
bone mass and density.
(1) Decreased thickness of the cortical and trabecular bone (Link 24-4)
(2) Radiographs of osteoporotic bone show osteopenia (a washed-out appearance).
f. Osteoporosis is more common in women than men. Men have greater bone mass to
begin with; therefore, it takes longer for them to develop osteoporosis.
g. Primary osteoporosis
(1) Affects 80% of women and 60% of men
(2) Subdivided into idiopathic (not discussed), type I (postmenopausal women), and type
II (involutional involving men and women)
h. Secondary osteoporosis
(1) Accounts for 20% to 40% of osteoporosis in both men and women
(2) Refers to osteoporosis that exists in other disease processes, inherited disease, or as a
result of a medication side effect

7. Paget disease (osteitis deformans)
• 1. Definition: Focal disorder of chaotic bone remodeling (both formation and resorption) that
results in thick, weak bone at risk for pathologic fractures
2. Epidemiology
a. Primarily occurs in men >50 years of age. Family history positive in 40% of cases.
b. Sites of involvement in descending order: pelvis, lumbar spine, sacrum or femur, skull,
tibia, humerus, scapula; uncommon in hand, foot, and fibula .
Pathogenesis
(1) Possible association with paramyxovirus infection of osteoclasts; possible genetic
factors
(2) Early phase of osteoclastic resorption of bone; produces shaggy-appearing lytic
lesions in the bone
(3) Late phase of increased osteoblastic bone formation
(a) Produces a markedly increased level of serum alkaline phosphatase (ALP)
(b) Produces thick, weak bone in a mosaic pattern (Link 24-10 A)
3. Clinical findings in Paget disease
a. Bone pain is the MC complaint.
b. Headaches and hearing loss occur if the skull is affected.
c. Hat size is increased with skull involvement. As an integration point, recall that
acromegaly caused by GH excess also increases hat size.
d. Clinical findings and complications
(1) Pathologic bone fractures
(2) Pain and swelling overlying the bone
(3) Increased risk for developing osteosarcoma or fibrosarcoma, malignancies of bone
(<1%)
(4) Increased risk for developing high-output heart failure (see Chapter 11); caused by
numerous arteriovenous (AV) connections in the vascular bone
•

8. Osteomyelitis
Definition:
Acute or chronic infection of bone; most commonly caused by a bacterium
and less commonly by fungi and viruses
1. Acute osteomyelitis
a. Staphylococcus aureus is the overall MC pathogen causing acute
osteomyelitis (70% to 89%) followed by Streptococcus (Streptococcus
pyogenes, viridans Streptococcus, Streptococcus pneumoniae).
Clinical feature;
• Bone pain with systemic sign of infection.( fever, leukocytosis).
• Lytic focus surrounded sclerosis of bone on x ray .
• diagnosis is made by blood culture.

9. • (a) S. paratyphi is the usual causative agent (50%–70% of cases).
.
(b) Common organisms include P. aeruginosa and Serratia marcescens.
Other pathogens include S. aureus and Eikenella spp.
• Direct implantation
(1) Direct implantation of P. aeruginosa caused by puncture of a foot through
rubber footwear produces a localized osteomyelitis.
(2) Prosthetic joints: microorganisms typically grow in biofilm, which protects
bacteria from antimicrobial treatment and the host immune response.

10. Chronic osteomyelitis; epidemiology
a.Treatment of refractory acute osteomyelitis (osteo) is the most frequent cause.
b. Approximately 10% to 30% of acute osteomyelitis progresses into chronic
osteomyelitis.
c. In elective trauma surgery, chronic osteomyelitis occurs in 1% to 5% after closed
fractures and, depending on severity, 3% to 50% after open fractures.
. Clinical findings of osteomyelitis include abrupt fever, bone pain (usually back in
86% of cases), and swelling.
. Diagnosis
Imaging studies: plain radiography, magnetic resonance imaging (MRI;
is the most accurate (test of choice for vertebral osteomyelitis),
technetium bone scan (detects early lesions), gallium scintigraphy with single-photon
emission computed tomography (SPECT).

11. Neoplastic disorders of bone; epidemiology
• 1. Metastasis is the MC malignancy of bone. Breast
cancer is the MC primary tumor that metastasizes to
bone.
2. Primary malignant tumors of bone, in descending
order of frequency
• Multiple myeloma , osteosarcoma, chondro sarcoma,
and Ewing sarcoma.

12. Joint Disorders
• A. Synovial fluid analysis
1. Routine studies performed on synovial fluid
include WBC count and differential, crystal
analysis, culture, and Gram stain.
2. Crystal identification
a. Monosodium urate (MSU)
(1) Definition: Needle-shaped (monoclinic) crystal
(2) Special polarization of the crystals shows negative
birefringence.
• Definition: A crystal that is yellow when parallel to
the slow ray of the compensator

13. • b. Calcium pyrophosphate
(1) Definition: Monoclinic-like or triclinic (rhomboid)
crystal
(2) Special polarization of the crystals shows positive
birefringence.
• Definition: A crystal that is blue when parallel to the
slow ray of the compensator

14. Classification of joint disorders
1. Group I
Noninflammatory joint disease
Examples: OA, neuropathic joint
2. Group II
Inflammatory joint disease
Examples: rheumatoid arthritis (RA), gout

15. Classification of joint disorders
3. Group III
Septic joint disease
Examples: Lyme disease (LD), disseminated
gonococcemia (GC)
4. Group IV
Hemorrhagic joint disease
Examples: trauma, hemophilia A and B

16. Signs and symptoms of joint disease
• 1. Arthralgia is a general term for joint pain.
2. Arthritis connotes inflammation of the joint associated with
pain, swelling, tenderness, and warmth.
3. Morning stiffness
Definition: Pain or stiffness in the joints that lasts >30
minutes.
Examples: RA, systemic lupus erythematosus (SLE),
polymyalgia rheumatic.
4. Abnormal joint mobility
Caused by damage to ligaments and the joint capsule
Example: a tear of the anterior cruciate ligament (ACL) in the
joint.

17. 5. Swelling of the joint (effusion)
Caused by increased joint fluid. Examples: exudate
(protein- and neutrophil-rich fluid),
blood.
6. Redness (rubor) and warmth (calor; “hot joint”) of
the joint
Examples: septic arthritis, RA
7. Joint crepitus with motion; refers to a crackling
feeling .

18. Osteoarthritis (OA)
Definition:
Progressive degeneration of articular cartilage that mainly targets
weight-bearing joints or joints that are used very frequently (e.g.,
joints in the hands and feet).
Epidemiology
a. Noninflammatory joint disease; no sex predilection
b. Almost universally present in those older than 65 years of age

19. Risk factors
• Advanced age
• Endocrine or metabolic conditions (acromegaly,
chondrocalcinosis, hemochromatosis, alkaptonuria
Osteochondritis dissecans.
• Obesity, trauma, neuropathic joint, meniscus injuries

20. • Common sites
(1) Femoral head, knee
(2) Cervical and lumbar vertebrae
(3) Hands (usually genetic)
• Less common sites.
(1) Shoulder, elbow
(2) Feet with the exception of the first metatarsophalangeal (MTP) joint
MTP joint is the site for bunion formation.
• Pathogenesis
Components of normal articular cartilage
(1) Proteoglycans (provide elasticity)
(2) Type II collagen (provides tensile strength)

21. • Clinical findings
(1) Osteophytes irritate the synovial lining.
(2) Bone rubs on bone.
(3) Hip OA may refer pain to the groin.
(4) Pain is aggravated with movement of the joint. Pain is caused by a secondary
synovitis from osteophytes
• Diagnosis of OA
a. Plain radiographs (Link 24-33 B)
b. MRI is good for synovial tissue abnormalities and effusions.
c. ESR and CRP are usually normal.
d. Synovial fluid is noninflammatory

22. Neuropathic arthropathy
Definition:
Noninflammatory joint disease secondary to a
neurologic disease. Loss of proprioception
(unconscious sense of position) and deep pain
sensation (loss of pain in the joint) leads to
recurrent trauma.

23. • Epidemiology; causes
a. Diabetes mellitus
b. Syringomyelia: degenerative disease of the cervical spinal cord
characterized by the presence of a fluid-filled cavity; primarily affects the
shoulder, elbow, and wrist joints.
c. Tabes dorsalis ;posterior columns of the spinal cord causing a loss of pain
sensation that primarily affects the hip, knee, and ankle joints

24. Rheumatoid arthritis
Definition:
Systemic disorder associated with chronic joint inflammation that most
commonly affects the peripheral joints (wrists, hands, feet).
Epidemiology
a. Female-to-male ratio is 3:1; prevalence, 1% of population.
b. In women, it typically occurs in the 30- to 50-year age bracket; MC joint disease in
women.
c. Various human leukocyte antigen (HLA) associations (HLA-DR4) that involve
intracellular signaling and production of certain types of synovial citrullinated
proteins.

25. Rheumatoid arthritis
Epidemiology
d. Microbial inciting agents that initiate synovial
inflammation include Epstein-Barr virus (EBV),
parvovirus B19, human herpesvirus 6, and Mycoplasma
spp.
e. Risk factors include age, female sex, tobacco use,
obesity.

26. Pathogensis(RA)
• Pathogenesis of joint disease may involve both type III and type IV
reactions.
a. One proposed mechanism is CD4+ helper T cells (cell-mediated type IV)
are activated, leading to release of pro inflammatory agents (e.g., TNF).
b. Inflamed synovial cells express an antigen that triggers B cells to
produce rheumatoid factor (RF). RF is an IgM autoantibody that has
specificity for the Fc portion of IgG.
c. Chronic synovitis and pannus formation eventually occur .
f. Pannus is granulation tissue that is formed within the synovial tissue by
fibroblasts and inflammatory cells.
d. Destroy the articular cartilage, leading to fusion of the joint by scar
tissue (called ankylosis). Bone erosions are caused by osteoclasts

27. Sjögren syndrome (SS)
Definition:
Autoimmune disease characterized by the destruction of minor salivary glands
(dry mouth) and the lacrimal glands (dry eyes).
Epidemiology
a. Primary and secondary subtypes (associated with other autoimmune diseases)
b. Female-dominant autoimmune disease (10:1 female-to-male ratio).
Clinical findings
Dry eyes described by the patient as “sand in my eyes”
Autoimmune destruction of the lacrimal glands
Xerostomia or dry mouth

28. Laboratory findings in SS
Anti–SS-A antibodies (anti-Ro; 60%-70%) and
anti–SS-B (anti-La; 40%-60%).
Anti–SS-B antibodies (anti-La) are present in
60% to 90% of cases.
Confirmation of SS is secured with a lip biopsy
showing lymphoid destruction of the minor
salivary gland.

29. Juvenile idiopathic arthritis
A type of arthritis in children <17 years of age that has
several subgroups with different clinical characteristics,
pathogenesis, and response to therapy.
Epidemiology
(1) Accounts for ~10% of all cases of JIA
(2) Peak age of onset is 2 to 4 years of age.
(3) Male:female sex ratio is equal (1:1).

30. Clinical findings
• Commonly presents as an “infectious disease” with fever
spikes once or twice a day,
sore throat, rash, polyarthritis, and generalized painful
lymphadenopathy.
• ( Extra articular features include rash, hepatomegaly, and
splenomegaly.
• persistent fever,prolonged prothrombin time and partial
thromboplastin time, liver dysfunction, hypertriglyceridemia,
and central nervous system (CNS) signs (coma, seizures).