Module 6: Bone: Osteoporosis, PTH, Rickets Flashcards
First lets start off with the basics of bone, what process is involved in the maturation and activation of osteoclasts?
RANKL on surface of osteoblasts binds RANK receptor on osteoclast
RANKL (on osteoblasts) is upregulated by what?
PTHRP
Vit D3
Some malignancies
What is secreted by osteoblasts and inhibits the RANKL-RANK interaction?
Osteoprotegrin (OPG)
There are two different mutations associations with Mesenchymal Condensation, the first is mutation in HOXD13, what does this lead to?
Synpolydactyly (extra digit between the 3rd and 4th finger with some degree of fusion)
The second mutation of mesenchymal condensation is RUNX2 (CBFA1), what does this lead to?
Cleidocranial dysplasia (open fontanelles, delayed closure of cranial sutures, primitive clavicles, delayed eruption of secondary teeth)
These cards follow the order of Oke and not class. The first pathology to discuss is Osteoporosis. What is the etiology?
Most commonly seen in elderly or
post menopausal women
–white and thin
–due to a lack of estrogen and thin b.c again less estrogen then obese
What is seen on slide 4, gross image?
Pic to left: normal vertebral body with vertical and horizontal lines and normal height
Pic to right: spinal vertebral body
–destruction of trabecular bone
–destroys horizontal trabeculae — compression fracture — loss of height and strength
What is the pathogenesis for osteoporosis?
Lack of estrogen — activation of T cells in the bone marrow — makes IL-6,IL-1,TNF alpha — activates osteoclasts – thinning of bone
makes IL-7 — premature apoptosis of osteoblasts —thinning of bone
–NET EFFECT IS EXCESSIVE OSTEOCLASTC ACTIVITY
What bones are fractured most often in osteoporosis?
Lumbar and Thoracic Spine (Compression fractures of the spine)
Distal forearm: ulnar and distal radius – colles fracture (falling on an outstretched hand)
Femur (neck)
What are the symptoms in a patient with osteoporosis?
Asymptomatic: incidental finding on DEXA scan (Bone density scan)
What investigations are done for osteoporosis?
DEXA scan: measure bone density should be done on post menopausal women over 60
X-ray: is not done b.c it is not sensitive (only finds late stages or pathological fractures)
Blood: Ca, PTH, PO4, and ALP: all normal because its a slow chronic process
Biopsy: thinning of bony trabeculae and because they are older there will be hypocellular marrow (So more fat cells)
What are the complications associated with osteoporosis?
- Pathological fractures: horizontal trabeculae are lost — compression fractures
- Colles Fracture
- Femoral Neck Fracture (most common)
- Fat Embolism Syndrome: 1-3 days post fracture – FA damaging the endothelium
- Bed ridden — stasis— DVT –PE (COD)
- Bed Ridden – pressure ulcers – secondary infection by S. Aureus
- Hospital acquired pneumonia
What is secondary osteoporosis due to?
Hyper PTH
Vit D or C deficiency
Corticosteriods
Moving on to the next topic of bone is Hyperparathyroidism. There are three types primary, secondary and tertiary. First we will tackle primary. what is the etiology?
Most common: solitary parathyroid gland adenoma (aka 1 gland)
or
Parathyroid Hyperplasia ( 4 glands)
–making PTH without negative feedback
In regards to primary hyper PTH there is sporadic and familial. What are some aspects of each
Sporadic: more common in older ppl
familial: young persons and part of MEN1 and MEN 2A (RET mutation)