Pathology of the musculoskeletal system 2016

BONE PATHOLOGY

BYF. CHAPIMA

B.Sc. (UNZA), MSc. Clinical Pathology (UNZA)

Introduction Musculoskeletal system is comprised of the

bones, joints and the muscles. Bones have three roles which are;

Mechanical support Mineral storage and Haematopoiesis.

Introduction ……………….

Mechanical functions of bone include;

Protection for the brain, spinal cord and chest organs;

Rigid internal support for limbs and Deployment as lever arms in the skeletal

muscle.

Introduction ………………. Joints (articulations) serve as a union

between bones and are necessary for the mechanical role of bone.

Lecture outlineBones1.Congenital diseases of bone2. Acquired diseases of bone development3. Fractures4. Osteonecrosis5. Osteomyelitis6. Metabolic bone disease7. Bone tumors

Congenital Diseases Of Bone Congenital diseases of bone range from

localized malformations to hereditary disorders associated with abnormalities affecting the entire skeletal system.

Can result in the absence of bones, extra bones, or inappropriately fused bones;

these are typically due to mutations in genes affecting localized migration and condensation of primitive mesenchymal cells

1. Achondroplasia Achondroplasia refers to a syndrome of short-

limbed dwarfism and macrocephaly, which represents a failure of normal epiphyseal cartilage formation.

It is the most common genetic form of dwarfism (1:15,000 live births) and is inherited as an autosomal dominant trait.

1. Achondroplasia………………. These people have normal mentation and life

spans. Pathogenesis Achondroplasia is caused by mutations in the

fibroblast growth factor receptor 3 (FGFR3) on chromosome 16.

1. Achondroplasia………………. The mutation inhibits proliferation and

differentiation of chondrocyte which impedes growth plate development.

Clinical features Clients have short stature The average height of an adult male is 131 cm

adult females is 124 cm.

1. Achondroplasia……………….

Have an average-size trunk, Short arms and legs Short arms have limited

range of motion at the elbows

A big head (macrocephaly) with a prominent forehead.

2. Scoliosis and Kyphosis Scoliosis is an abnormal lateral curvature of the

spine, usually affecting adolescent girls. Kyphosis refers to an abnormal anteroposterior

curvature. When both conditions are present, the term

kyphoscoliosis is used.

2. Scoliosis and Kyphosis …………….

Pathogenesis A vertebral body grows in length (height) from

the endplates of the vertebrae, which correspond to the growth plates of long tubular bones.

As in tubular bones, vertebral bodies increase in width by appositional bone growth from the periosteum.

2. Scoliosis and Kyphosis ……………. In scoliosis, for unknown reasons, one portion of

the endplate grows faster than the other, producing lateral curvature of the spine.

Clinical features If kyphoscoliosis is severe, the patient may

develop, corpulmonale and joint problems particularly involving the hip.

2. Scoliosis and Kyphosis …………….

Treatment

The treatment of scoliosis is appropriate stress on the vertebral body through the use of braces or internal fixation to straighten the spine.

3. Osteogenesis Imperfecta (OI) OI refers to a group of genetic (mainly

autosomal dominant) disorders of connective tissue due to mutations in the gene for type I collagen.

It affects the skeleton, joints, ears, ligaments, teeth, sclerae and skin

It is characterized by hard and easily broken bones often from little or no apparent cause.

3. Osteogenesis Imperfecta …………

Pathogenesis The pathogenesis of OI involves mutations of

COL1A1 and COL1A2 genes which encode the α1 and α2 chains of type I procollagen, the major structural protein of bone.

These genes are located in chromosomes 17 and 7 respectively.

3. Osteogenesis Imperfecta ………… Mutations causes substitution of other amino

acids for the glycine type I collagen at every third residue.

Clinical features This depends on the type of OI

3. Osteogenesis Imperfecta ………… Type I Mildest form Multiple fractures when child begins walking and

sitting Blue sclera (thin sclera with underlying choroids) Hearing abnormalities (fusion of ossicles)

beginning in early 20s or 30s. Extremely thin and curved bones and bluish

yellow teeth


Type II Most severe form. Numerous fractures and

severe bone deformity. Small stature with

underdeveloped lungs.


Type III Short stature. Barrel-shaped rib cage. Bone deformity, often

severe. Brittle teeth possible. Hearing loss possible.


Type IV Similar to type I White sclera Bone cortex may mature during adolescence or

afterwards

Lecture outlineBones1. Congenital diseases of bone2.Acquired diseases of bone

developmenta) Fracturesb) Osteonecrosisc) Osteomyelitis

3. Metabolic bone disease4. Bone tumors

1. Fractures

The fracture is the most common bone lesion and is defined as a discontinuity of the bone .

Pathogenesis The lesion typically results from blunt trauma to

the muscle and soft tissues, usually of the lower limb; however, some cases occur spontaneously.

1. Fractures ………….

Fractures can be classified as traumatic, pathological or stress fractures

Common causes

Trauma. A fall, a motor vehicle accident, or trauma during a football game can all result in fractures.

1. Fractures …………. Pathological fractures - Osteoporosis. This

disorder weakens bones and makes them more likely to break (pathological fractures).

Overuse. A stress fracture refers to an accumulation of stress-induced micro fractures, which eventually result in a true fracture through the bone cortex.

They can result from repeated mechanical injury. Stress fractures are more common in athletes.

1. Fractures ………….Common types of fractures Stable fracture. The broken

ends of the bone line up and are barely out of place.

Open or compound fracture. The skin is pierced by the bone that breaks the skin at the time of the fracture.

The bone may or may not be visible in the wound.

1. Fractures …………. Transverse fracture. This

type of fracture has a horizontal fracture line.

Oblique fracture. This type of fracture has an angled pattern.

Comminuted fracture. In this type of fracture, the bone shatters into three or more pieces.

1. Fractures ………….Signs and Symptoms Pain on the affected area Un able to move the injured limb. Other common symptoms include: Swelling and tenderness around the injury area Bruising Deformity — a limb may look "out of place" or a

part of the bone may puncture through the skin

2. Osteonecrosis Osteonecrosis (ON) refers to death of bone in

the absence of infection.Causes/ Risk factors Long-term steroid treatment Alcohol abuse Joint injuries Having diseases such as arthritis and cancer

2. Osteonecrosis …………..

Pathogenesis Cancellous bone and cortex undergo different

mechanisms of repair. Necrotic cancellous bone heals by creeping

substitution, in which the necrotic marrow is replaced by invading neovascular tissue, thus providing the pluripotential cells necessary for bone repair.

2. Osteonecrosis ………….. In non-traumatic ON there is embolization by

blood clots or lipid droplets. This leads to the death of osteocytes and bone

marrow followed by the repair processes to remove necrotic bone and marrow and replace them with viable tissue.

If the infarct is small, this process may succeed.

2. Osteonecrosis ………….. However, in some patients,

the process is not successful and the infarct gradually collapses.

The overlying articular surface becomes flattened and irregular, causing increased pain and eventually leading to osteoarthritis.

2. Osteonecrosis …………..

Symptoms and Signs Patients may remain asymptomatic for weeks to

months after the vascular insult. Pain then develops gradually with progressive

collapse of the joint Pain increases and is worsened by motion and

weight bearing and is relieved by rest.

3. Osteomyelitis

Osteomyelitis is an inflammation of the bone and the bone marrow.

Causes Commonly caused by Staphylococcus aureus

(Pyogenic Osteomyelitis) and Mycobacterium

tuberculosis (Tuberculous Osteomyelitis)

3. Osteomyelitis ……………..

Micro – organisms can enter a bone in 3

ways;

Via the bloodstream

From a nearby infection Direct contamination.


Pathogenesis Osteomyelitis primarily affects the metaphyseal

area because of vascular supply in this region If the organism is virulent and continues to

proliferate, it creates increased pressure on the adjacent thin-walled vessels in the marrow cavity.


Such pressure further compromises the vascular

supply in this region and produces bone

necrosis.

The necrotic areas coalesce into an avascular

zone thereby allowing further bacterial

proliferation.


Signs and symptoms Fever or chills Irritability or lethargy in young children Localized bone pain Swelling, warmth and redness over the area of

the infection

3. Osteomyelitis …………….. Sometimes osteomyelitis

causes no signs and symptoms or has signs and symptoms that are difficult to distinguish from other problems.

3. Osteomyelitis ……………..Complications Osteonecrosis - Bone death Septic arthritis Impaired growth Skin cancer. If osteomyelitis has resulted in an

open sore that is draining pus, the surrounding skin is at higher risk of developing squamous cell cancer.

4. Tuberculosis of Bone Tuberculosis of bone originates from the lung

or lymph nodes, and reaches the bone by haematogenous spread.

Often affects the spine, termed as Tuberculous spondylitis or Pott disease is a complication of childhood tuberculosis and affects the bodies of the vertebrae, with sparing of the lamina

The thoracic vertebrae are most commonly affected.

4. Tuberculosis of Bone ……………

Pathology The pathology in Tuberculous spondylitis is

similar to tuberculosis at other sites. The granulomas first produce caseous necrosis

of the bone marrow, which leads to slow resorption of bony trabeculae and, occasionally, to cystic spaces in the bone.

4. Tuberculosis of Bone ……………

Because there is little or no reactive bone formation, affected vertebrae usually collapse, leading to kyphosis and scoliosis.

The intervertebral disk is crushed and destroyed by the compression fracture, rather than by invasion of organisms.

Lecture outlineBones1. Congenital diseases of bone2. Acquired diseases of bone development

a) Fracturesb) Osteonecrosisc) Osteomyelitis

3.Metabolic bone disease4. Bone tumors

1. Osteoporosis Osteoporosis AKA “porous

bone” is a disease characterized by increased sponginess of the bone resulting from reduced bone mass.

Classifications Osteoporosis can be primary or

secondary due to some other factor.

1. Osteoporosis ……………Primary disorder can further be classified as; Type 1 or postmenopausal osteoporosis is

associated with decreased levels of oestrogen and has a greater effect on trabecular than cortical bone.

Type 2 or senile osteoporosis is a consequence of aging and is often augmented by inadequate calcium and vitamin D intake.

1. Osteoporosis ……………Peak bone mass Osteoblasts and osteoclasts (cells that resorb

bone) are regulated by parathyroid hormone (PTH), calcitonin, estrogen, vitamin D, various cytokines, and other local factors such as prostaglandins.

Normally, bone formation and resorption is closely balanced.

1. Osteoporosis …………… Under normal conditions, bone mass peaks

between the ages of 25 and 35 years and declines thereafter.

Blacks reach higher bone mass than whites Men have higher bone mass than women. After achieving peak for about 10 years, bone

loss occurs at a rate of about 0.3 to 0.5%/yr.

1. Osteoporosis ……………

In menopause, bone loss is accelerated to about

3 to 5%/year for about 5 to 7 years and then the

rate of loss slows.


Pathogenesis Osteoporosis occurs when bone loss exceeds

bone formation, resulting in a low bone mass. Thus, this disease should be viewed in the

context of failure of the remodelling cycle to replace all the resorbed bone.


1. Osteoporosis ……………Risk Factors Race (Caucasians > African Americans) Sex (F > M) Physical inactivity Slender body build Early menopause Increasing age Calcium nutritional state - insufficient dietary

intake.

1. Osteoporosis ……………Signs and Symptoms Patients with osteoporosis are

asymptomatic unless a fracture has occurred.

Gross morphology The trabecular plates become

perforated, thinned, and lose their interconnections, leading to progressive micro fractures.

2. Osteomalacia and Rickets

Osteomalacia refers to a softening of bones, often caused by vitamin D deficiency in adults.

Rickets is the softening and weakening of bones in children, usually because of an extreme and prolonged vitamin D deficiency.

2. Osteomalacia and Rickets …………..

Pathogenesis Vitamin D promotes the absorption of calcium

and phosphorus from the gastrointestinal tract. Deficiency of vitamin D makes it difficult to

maintain proper calcium and phosphorus levels in bones, which can cause soft bones .

Soft bones are more likely to bow and fracture than are harder and healthy bones.

2. Osteomalacia and Rickets …………..

Sign and symptoms The most common

signs and symptoms are bowled legs.

3. Paget’s disease of the bone Paget disease ( osteitis deformans) is a localized

disorder of bone remodeling, resulting in excessive bone resorption followed by disorganized bone replacement, producing thickened but weak bone that is susceptible to deformity and fracture.

3. Paget’s disease of the bone……….. It is related to a virus infection with

paramyxovirus, and also possibly to have a genetic predisposition.

Paget disease begins after age 40 years and is common in those of European ancestry.

3. Paget’s disease of the bone………..

Pathogenesis Paget disease develops in 3 stages: The osteolytic stage ( osteoclastic activity

predominates) The mixed osteolytic-osteoblastic stage The osteosclerotic stage (osteoblastic activity

predominates in this "burnout stage")

3. Paget’s disease of the bone………..Pathology Involved bones are thick but weak and fracture

easily. Skull involvement leads to increased head size

and foraminal narrowing that can impinge on cranial nerves, often leading to deafness.

Involvement of facial bones may produce a lion-like face.

3. Paget’s disease of the bone………..

Complications Arteriovenous shunts within marrow, which may

result in high-output cardiac failure Increased incidence of osteosarcoma and other

sarcomas.

Lecture outlineBones1. Congenital diseases of bone2. Acquired diseases of bone development

a) Fracturesb) Osteonecrosisc) Osteomyelitis

3. Metabolic bone disease4.Bone tumors

Benign tumors of bone

Osteoma is a benign neoplasm that frequently involves

the skull and facial bones. Osteoma can be associated with Gardner

syndrome.

Benign tumors of bone………………Osteoid Osteoma Osteoid Osteoma is a benign, painful growth of

the diaphysis of a long bone, often the tibia or femur.

It affects males more than females, with peak age 5 to 25 years.

The pain tends to be worse at night and relieved by aspirin.

Benign tumors of bone……………… X-rays studies show central radiolucency

surrounded by a sclerotic rim. Microscopically, these tumors show a small (<2

cm) lesion of the cortex characterized by a central nidus of osteoid surrounded by dense sclerotic rim of reactive cortical bone.

Benign tumors of bone………………

Osteoblastoma Osteoblastoma is a tumor that is similar to an

osteoid osteoma but is larger (>2 cm) and often involves vertebrae.

Benign tumors of bone………………

Osteochondroma Osteochondroma (exostosis) is a benign bony

metaphyseal growth capped with cartilage that originates from epiphyseal growth plate.

It typically presents in adolescent males who have firm, solitary growths at the ends of long bones.

Benign tumors of bone……………… Osteochondromas may be Asymptomatic Cause pain Produce deformity or Undergo malignant

transformation (rare)

Malignant tumors of boneOsteosarcoma Osteosarcoma ( osteogenic sarcoma) is the most

common primary malignant tumor of bone, and the tumor occurs more frequently in males than females.

Most cases occur in teenagers (ages 10-25 years), and patients with familial retinoblastoma have a high risk.

Malignant tumors of bone……………… Secondary osteosarcomas occur in elderly

persons. These highly aggressive tumors are associated

with Paget disease, irradiation, and chronic osteomyelitis.

Malignant tumors of bone………………Clinically localized pain and swelling. The classic x-ray findings are

Codman triangle (periosteal elevation), "sunburst“ pattern, and bone destruction.

The treatment is with surgery and chemotherapy.

The prognosis is poor

Malignant tumors of bone………………

Pathology Grossly, osteosarcoma often involves the

metaphyses of long bones, usually around the knee (distal femur and proximal tibia).

The tumor produces a large, firm, white-tan mass with necrosis and hemorrhage.

Malignant tumors of bone………………

Chondrosarcoma Chondrosarcoma is a malignant tumor of

chondroblasts that may arise de nova or secondary to a pre-existing enchondroma or Paget disease.

Males are affected more frequently than females, with peak age 30—60 years.

Malignant tumors of bone……………… Chondrosarcoma presents with enlarging mass

with pain and swelling, and it typically involves the pelvic bones, spine, and shoulder girdle.

Malignant tumors of bone………………Ewing sarcoma Ewing sarcoma is a malignant neoplasm of

undifferentiated cells arising within the marrow cavity.

Males are affected slightly more often than females.

Most cases occur in teenagers (age range 5-20 years).

Malignant tumors of bone………………Clinically Patients present with pain, swelling, and

tenderness. X-ray studies show concentric "onion-skin"

layering of new periosteal bone. The tumor is treated with chemotherapy,

surgery, and/or radiation, and has a 5-year survival rate of 75%.

Malignant tumors of bone………………Metastatic Tumors Metastatic Tumors are the Most Common

Malignant Tumors in Bone Most metastatic lesions to bone are carcinomas,

particularly of the breast, prostate, lung, thyroid and kidney.

It is estimated that haematogenous skeletal metastases are found in at least 85% of cancer cases that have run their full clinical course.

Malignant tumors of bone……………… The vertebral column is, by far, the most

common site in adults, and the appendicular skeleton is the typical location in children.

Wednesday 3 May 2023 79

References Robbins, S.L, Kumar, V and Abbas, K (2010). Pathologic

Basis of Disease (8th Edition). W.B Saunders Company, Philadelphia.

Robbins SL and Kumar V (2007). Basic Pathology (8th Edition).WB Saunders Co. London.

Harsh Mohan, (2010). Textbook of Pathology (6th Edition). Jaypee brothers medical publishers (p) ltd, India

Riede and Werner, Color Atlas of Pathology © 2004 Thieme

Rubin E, Rubin R, Strayer D.S. (2012) Rubin`s Pathology: Clinicopathologic Foundations of Medicine (6th Edition), Lippincott Williams & Wilkins, a Wolters Kluwer business. Philadelphia, PA.

Health & Medicine

Pathology of the musculoskeletal system 2016