Bone

Pathology

Condition

Calciu Phospha Alkaline

m
te
phosphat
ase

Parathy
roid
hormon
e

Comments

Osteitis
fibrosa
cystica

Brown
tumors

Osteomala
cia &
rickets

Soft bones

Osteopetro
sis

Thick, dense
bones also
known as
marble bone

Osteoporos
is

Decreased
bone mass

Pagets
disease of
bone

Variable
(dependin
g on stage
of disease)

Abnormal
bone
architecture

Osteoporosis

Overview
Progressive bone disease
Decrease in bone mass & density
Increased risk of fracture
BMD
deteriorated bone micro-architecture
changed amount & variety of protein
Established osteoporosis if fragility fracture

Epidemiology
~ 33% of women and 10% of men
above 50 yr age have osteoporosis

Types
Primary type 1:
= postmenopausal osteoporosis
In women after menopause

Primary type 2:
= senile osteoporosis
>75 yr
F:M = 2:1

Secondary osteoporosis:
Any age
F:M = 1:1
Due to chronic medical problem or drugs

Symtoms & Signs

No symptoms
risk of fractures
Fragility fractures
Fractures:
Debilitating acute and chronic pain in elderly
May also be asymptomatic
Most common: wrist, spine, shoulder, hip
Vertebral collapse (compression fracture): sudden back
pain with radicular pain
Multiple vertebral fractures: Dowagers hump
risk of falls in elderly fractures

Risk factors - 1
Nonmodifiable:
Advanced age
Female sex (post-menopausal or postoophorectomy in estrogen)
Race ( risk in European and Asian
ancestry)
Heredity ( risk if family history)
Previous fracture
Small stature

Risk factors - 2
Potentially modifiable:
Excess alcohol
Vitamin D deficiency
Tobacco smoking
Malnutrition
High dietary protein
Underweight/inactive
Endurance training (in females)
Heavy metals (esp. cadmium)
Soft drinks

Risk factors - 3
Medical disorders:
Immobilization (Use it or lose it)
Hypogonadal states ( estrogen in females, testosterone in males),
e.g. Turner syndrome, Klinefelter syndrome, bilateral oophorectomy
Endocrine disorders, e.g. Cushings syndrome, hyperparathyroidism,
hyperthyroidism, hypothyroidism, DM type 1 & 2
Malnutrition, parenteral nutrition, malabsorption
Rheumatologic disorders, e.g. rheumatoid arthritis, ankylosing
spondylitis, SLE
Renal insufficiency
Hematologic disorders, e.g. multiple myeloma, lymphoma
Inherited disorders, e.g. osteogenesis imperfecta, Marfan syndrome
Scoliosis of unkown cause
Parkinsons disease

Risk factors - 4
Drugs:
Steroids (glucocorticoids, esp. prednisone)
Anti-epileptics
Thyroxine
Drugs that induce hypogonadism, e.g.
methotrexate
Anticoagulants (heparin & warfarin)
Proton pump inhibitors
Thiazolidinediones (used for DM), e.g.
rosiglitazone
Lithium

Pathogenesis

Imbalance between bone resorption and bone formation

Matrix remodeling of bone (10%)
Resorption: osteoclast cells
Formation: osteoblast cells
3 mechanisms:
peak bone mass
bone resorption
bone formation during remodeling

Estrogen
Calcium metabolism
Trabecular bone ( = cancellous bone) is more vulnerable than
cortical bone
Hence common fracture sites: wrist, hip, spine

Diagnosis
Conventional X-ray (cortical thinning,
increased radio-lucency, vertebral
fracture)
Measure BMD by dual energy x-ray
absorptiometry

Management
Lifestyle:
Smoking cessation
Decrease alcohol intake
Weight-bearing endurance exercises
Fall prevention

Nutrition:
Supplementation with calcium and vitamin D is
controversial

Drugs:
Bisphosphonates (e.g. alendronate)

Osteomalacia

Osteomalacia
Softening of bones
Cause: Defective bone mineralization due to
phosphorus or calcium; or overactive resorption of
calcium due to hyperparathyroidism
Most common cause: deficiency of vitamin D
Rickets
Clinical features:
Bone pain
Typical waddling gait
Pathologic fractures
X-ray shows pseudo-fractures (Loosers zones)

Treatment: Vitamin D

Osteopetrosis

Osteopetrosis

= Marble bone disease

= Albers-Schonberg disease
Extremely rare
Inherited disorder
Bones harden, becoming denser (osteopetrosis = stone bone)
Pathogenesis:
malfunctioning osteoclasts
Deficiency of carbonic anhydrase in osteoclasts defective hydrogen ion
pumping by osteoclasts defective bone resorption

Clinical features:
Brittle bones
Stunted growth, deformity, increased likelihood of fractures
Bone expansion bone marrow narrowing anemia, hepatosplenomegaly
Bone expansion blindness, facial paralysis, deafness

Treatment: bone marrow transplant

Osteitis fibrosa cystica

Osteitis fibrosa
cystica

= von Recklinghausens disease of bone

Hyperparathyroidism osteoclast activity serum calcium + weak bones & cyst-like
brown tumors in bone
Causes of hyperparathyroidism:
Parathyroid adenoma
Hereditary factors (e.g. MEN type 1)
Parathyroid carcinoma
Renal osteodystrophy (ESRD calcitriol PTH)

Clinical features:
Bone pain or tenderness
Bone fractures
Skeletal deformities (e.g. bowing of bones)
Hyperparathyroidism kidney stones, nausea, constipation, fatigue, and weakness
X-rays: thin bones, fractures, bowing, cysts

Treatment:
I/V vitamin D
Parathyroidectomy

Pagets disease of bone

Pagets disease of
bone

Enlarged and mis-shapen bones

Pathogenesis: Excessive breakdown and formation
of bone, followed by disorganized bone remodeling
Localized to one or few bones
Causes: viral, genetic
Clinical features:
Bone pain
Gross deformity of bones
Deafness, Blindness
Rarely: Pagets sarcoma

Treatment: Bisphosphonates, calcitonin, surgery

Bone tumors

Bone tumors

Bone tumors
1o and 2o bone tumors
2o :
Most commonly from prostate, breast, lung, thyroid, kidney
50-100 times more common than 1o cancers

1o :
may be benign or malignant
most common locations are distal femur and proximal tibia
Benign: osteoma, osteochondroma, osteoblastoma, endochondroma, giant
cell tumor of bone, aneurysmal bone cyst, fibrous dysplasia of bone
Malignant: osteosarcoma, chondrosarcoma, Ewings sarcoma, fibrosarcoma
(Multiple myeloma is a blood cancer originating in bone marrow)

Clinical features:
Progressively increasing bone pain
Pathologic fractures, etc

Treatment: Chemotherapy, Radiotherapy, Surgery