Skeletal System Pathology ANSWERS

A. Diseases of disordered synthesis/resorption

1.1 Paget’s disease of tibia
1.2 Paget’s disease of skull
1.3 Brain from Paget’s disease patient

Question 1


a. What are 2 complications of Paget's disease of bone and why might they occur?
Deformed bone (weight bearing in weak bones), pathologic fractures (weak bone less resistant to external
forces), pain, compression of cranial nerves which may cause deafness or visual disturbances as a result of
bony foramina for acoustic and optic nerves becoming narrower due to abnormal bone increasing in
thickness, osteosarcoma, hydrocephalus resulting from narrowing of foramina which obstructs
cerebrospinal fluid flow.
2.1 Osteoporosis NO SPECIMEN
2.2 Osteomalacia (in adult) & rickets (in child)
Question 2

a. What factors predispose an individual to osteoporosis?

Factors include ageing, reduced physical activity, amenorrhea, loss of oestrogenic activity after the
menopause and low initial bone mass.

b. Osteoporosis results in excessive loss of osteoblasts but their demise does not result in inflammation
so what form of cell death is occurring?
Apoptosis

c. What are the consequences of renal failure on the skeletal system?

Chronic renal failure can cause osteomalacia (under mineralization of bone) although a better term, given
that the cause is kidney failure is renal osteodystrophy. In failure, the kidney may not be able to synthesise
the active metabolite of vitamin D (activated by chemical changes in the kidney) and without active
vitamin D the gut cannot absorb calcium from food, which results in low levels of serum/blood calcium.

The control of the plasma concentration of calcium is finely controlled, parathyroid hormone (PTH) is
released in response to low serum calcium and promotes resorption of calcium from bones by osteoclasts
and induces the kidney to retain calcium in blood, excrete phosphate and activate more vitamin D. In renal
failure, less vitamin D is activated and calcium is lost in urine so serum levels decline resulting in increased
PTH secretion. The result is liberation of calcium from bones which forms complexes with the high levels of
phosphate in the blood which can be deposited in soft tissues including arterial walls and heart valves
while any free calcium is destined to be lost in urine as the kidneys no longer respond to PTH.

In addition, the effects of increased metabolic wastes and lethargy from lack of EPO/anaemia ensures that
individuals with renal failure find exercise and physical activity in general a challenge and so muscle
atrophy is usually observed. Muscle contraction is a stimulus for bone remodelling, the stronger the
muscles and the greater the stress they inflict, the stronger the bones become in growth and the better
they are maintained in adult life.
B. Bone Tumours
Benign neoplasms of bone

3.0 Osteochondroma (also known as osteocartilaginous exostosis)

Malignant primary neoplasms of bone
3.1 Bone marrow malignancies: Multiple myeloma - plasma cell malignancy

3.2 Osteogenic sarcoma (osteosarcoma)

Peak incidence is in second decade of life; about 50% occur around the knee more often in the distal femoral epiphysis than in the
proximal tibial metaphysis - these are the sites of greatest skeletal growth activity.

Osteosarcoma of:
1) Femur

2) Epiphyseal region of left tibia

3) Tibia

4) Lung (secondary deposits)


Question 3


a. Osteosarcoma has a bimodal age distribution; about 75% of osteosarcomas occur in young people,
why?
Bone is actively growing in young people and most osteosarcomas occur in the actively growing
epiphyseal plates. Increased proliferation is a major risk factor in the development of cancer. Once the
active growth of bones has been completed the risk of developing osteosarcoma plummets.

A smaller second peak of osteosarcoma is found in elderly people who frequently suffer from conditions
such as Paget’s disease and bone infarcts. How might Paget’s disease increase the risk of developing
osteosarcoma? Paget’s disease is characterised by hectic osteoclastic bone resorption followed by bouts
of bone formation. The proliferation associated with the laying down of new bone increases the risk of
osteosarcoma. In a similar manner, proliferation is associated with repair of bone infarct.

3.4 Ewing’s tumour

This tumour tends to occur before the age of 20 years and is the second most common sarcoma in children after osteosarcoma. The
specimen shows Ewing's tumour in a 15-year-old male, treated with both radio and chemotherapy. The duration of disease from
diagnosis to death was 13 months with secondary tumours found at post-mortem in lungs, skull, ribs, ileum and kidney.

b. From what you have learnt this semester, what can you surmise is the reason why Ewing’s tumour is
not named after the cell in which it originates?
It is not known what the cell of origin is but it is an embryonic cell that has never fully differentiated

Secondary malignancies in bone

4.0 Prostatic carcinoma metastases in vertebra and skull
Prostatic carcinoma metastases in vertebra and skull have stimulated new bone formation - note the increased thickness of the skull
bone. (Osteosclerosis - abnormal increase in thickening and density of bone)
4.1 Metastases in vertebra

4.2 Lung carcinoma metastases in bone

Spinal metastases from a small cell carcinoma of the lung from a male aged 63.

Question 4


a. Why is the bone so commonly affected by metastases?

Bone is very vascular, so arterial metastases are easily distributed to this site plus it’s a good site for
tumour cells to become trapped. Bone metastases are found in more than 25% of people who die from
cancer over all but 75% of people who die from breast cancer.

C. Osteomyelitis
[Gr. Osteon - bone; myelos - marrow; itis - inflammation] Osteomyelitis may be a complication of any systemic infection but it
frequently manifests in the skeleton as a primary solitary focus of disease. All types of organisms can cause osteomyelitis but
infections caused by certain pyogenic bacteria and mycobacteria are the most common.
Infectious organisms reach the bone by:
Haematogenous spread
Direct extension from adjacent infected site Direct traumatic

5.0 Acute osteomyelitis of sterno-clavicular joint

5.1 Chronic osteomyelitis of vertebral body, which led to vertebral collapse

5.2 Chronic osteomyelitis of left tibia with sinus tract communicating with skin.
Note also the presence of squamous cell carcinoma, Marjolin’s ulcer, a malignant ulcerating growth occurring in scar tissue or at the
epithelial edge of a chronic ulcer.

Question 5

a. Under what circumstances would acute osteomyelitis become chronic?

Going back to general principles, the inflammation will become chronic if the stimulus remains, if acute if
repeated or in special cases including some infections and autoimmune disease. So in bone, if bacteria are
not killed, the stimulus for the inflammation will remain and body’s defence response gradually changes
from acute to chronic. Also in osteomyelitis, bone fragments become necrotic as their blood supply is
compromised by the infection. These dead pieces of bone act like foreign bodies (like a splinter) and keep
the inflammation going. These dead pieces of bone (called sequestrum) may need to be surgically
removed before complete healing can occur.

b. What main cellular changes distinguish acute from chronic inflammation?

Acute inflammation is of short duration and characterised by lots of neutrophils, hyperaemia and
inflammatory exudate, while chronic inflammation is of long duration and involves lymphocytes, tissue
destruction and repeated attempts to repair. Chronic inflammation occurs secondary to a persistent acute
inflammation or as a primary response to some “special” agents e.g. tubercle bacilli, silica and asbestos.

5.3 Fractured neck of femur

Osteomyelitis developed subsequent to insertion of an S.P. nail (Smith-Petersen nail: a flanged nail for stabilizing fractures of the
neck of femur).
5.4 History of pathological fracture
Cavernous haemangioma of the right buttock in a female aged 18. The right leg had been amputated at the age of 9 because of a
pathological fracture secondary to very extensive haemangiomatous involvement of bone. Small haemangiomas were also found in
the liver, spleen and adrenals at autopsy. Death was due to pulmonary embolism.

Question 6


a. What is a pathologic fracture & what are some common causes?

A fracture that occurs in a bone already affected by disease thus it requires less force to break. All of the
diseases covered today increase the risk of pathologic fracture including osteoporosis, osteomalacia,
Paget’s, chronic renal failure, primary & secondary tumours, osteomyelitis and joint diseases.

D. Joint Diseases Arthritis

6.0 Chronic gout
Deposition of crystals of uric acid from breakdown of DNA (acute and chronic tophaceous forms).
1) Urate deposits (white) in metatarso-phalangeal joint
2) Gouty tophi in metacarpo-phalangeal joints

3) Gouty deposits on cartilage of patella

6.1 Osteoarthritis
Wear and tear degeneration of cartilage
6.2 Rheumatoid arthritis
Rheumatoid arthritis is an autoimmune disease in which joint is often severely damaged by chronic inflammation of synovial
membrane. May have clinical exacerbations resulting in acute inflammation in addition to the constant chronic condition.
6.3 Rheumatoid arthritis
The specimen shows severe rheumatoid arthritis with extensive chronic inflammation (proliferative) of the condyles and deep
erosions of the femur. Pannus, the proliferative inflammatory tissue developed from the synovial membrane in response to attack
by immune system has “invaded” and destroyed the bone.
Question 6


a. How do osteoarthritis and rheumatoid arthritis differ in their aetiologies?

Osteoarthritis is a wear and tear degeneration of
joints and so tends to affect weight bearing joints in body. Typically it affects women in middle age
the elderly or people who have engaged in sports
such as netball and running. There is little
inflammation just a loss of cartilage which is
treated by joint replacement.
Rheumatoid arthritis is an autoimmune destruction
of joints that may affect any synovial joint in the
more than men but it can occur in anyone. The
joints are affected by chronic inflammation (type IV
cell mediated response), which may at times be
superimposed by acute inflammation during which
the joints are swollen, red and warm to touch.
During these flare-ups, movement may improve the
pain and loss of function however the destruction
of the joint and scarring means that in many people
the condition gets progressively worse with
increasing deformities and functional loss. Anti-
inflammatory drugs and TNF-α inhibitors offer
some alleviation of symptoms.