233. Metabolic Disease

Question 1

Osteogenesis imperfecta

Type, genetic, effect, problem, histo

Answer 1

Abnormal Matrix disease (“brittle bone”)
AR most severe, defect in type 1 collagen
E: bone fractures, hearing defects, dentin of teeth, blue sclera of eye, early OA
Problem with formation of Primary Bone Trabeculae
Histo: no osteons, no bands of type I collagen

Question 2

Osteoporosis

Type, Histo, Process, Pathogenesis

Answer 2

Too little matrix
Histo: normal bone just less quantity
>1 atraumatic fractures, low mineral bone density
Process: 1. Localized: immobility, inflammatory focus around bone (like RA) 2. Generalized: Senile/Post-Menopausal, may occur with endocrinopathy, DM I, OI, drugs

Pathogen: subsequent loss of bone that occurs with age, osteoblasts lose ability to form new bone, osteoclasts activated

Question 3

Difference between post-menopausal osteoporosis and senile osteoporosis

Answer 3

PM OP: estrogen deficiency upregulates osteoclastogenic factors; HIGH TURNOVER OP - osteoclast activity > osteoblast activity (still active blasts!)

S OP: M+W>70y/o; due to decreased osteoblast reproductive potential and less potent growth factors; LOW TURNOVER OP (less osteoblasts, normal osteoclasts)

Question 4

Mucopolysaccharidosis

type of disease, pathogenesis, sx, genetics

Answer 4

too little matrix disease
P: mutations in lysosomal enzymes - can’t degrade GAGs - accumulate and cell damage
sx: cardiac valve disease, mental retardation, hepatosplenomegaly
Defects in enchondral ossification - short stature and hypoplastic teeth, osteoporosis, joint stiffness, late secondary OA
Genetics: most classes AR (1 XLR - Hunters)

Question 5

Hyperparathyroidism

type, pathogenesis, sx

Answer 5

Too much bone resorption
P: Primary HPTH - PTH adenoma or chief cell hyperplasia; Secondary HPTH - PTH hyperplasia due to chronic renal failure

High PTH = osteoclastogenesis = osteoporosis in cortical bone
“Dissecting Osteitis” railroad track of bony trabeculi due to central osteoclast resorption
Subperiosteal cortical bone resorption

Question 6

Paget’s Disease of Bone

type, phases, pathogenesis, imaging, histo

Answer 6

too much bone resorption
“collagen matrix madness” - dyssynchrony of osteoclasts/blasts
marked bone resorption then rapid new bone formation
Phases: 1. Osteolytic, 2. Mixed Osteoclastic/blastic, 3. Sclerotic
P: upregulation of NF-kB = osteoclastogenesis; mutated p62- regulator of RANKL mediated osteoclastogenesis - sensitises osteoclasts to RANKL = increased resorption activity/capacity (triggered by paramyxovirus)
XR: lytic bone lesions
Histo: highly vascularized stroma, enlarged osteoclasts during osteolytic phase, osteosclerotic: haphazard mosaic wall to wall sheets of mineralized bone

Question 7

Osteopetrosis

type, features, imaging, histo

Answer 7

too little bone resorption
Absent/defective osteoclast activity (mutated H-ATPase - cant acidify bone to break it down) = abnormally thickened bone
Features: Fractures (no osteon formation), anemia/thrombocytopenia (lose hematopoiesis), extramedullary hematopoiesis, infections/Cranial nerve defects
XR: sclerotic medullary cavity
Histo: medullary bone marrow replaced by calcified cartilage and new bone (mosaic formed new bone)