MSK: 419 - 421 Flashcards
What process is inhibited in achondroplasia?
Impaired endochondral ossification because of impaired cartilage proliferation in the growth plate
What is the inheritance of hereditary achondroplasia?
Autosomal dominant
What is the mutation in achondroplasia?
Activating mutation of fibroblast growth factor receptor (FGFR3)
Is membranous ossification affected in achondroplasia?
No
What does a patient with achondroplasia look like?
Head that appears relatively large (actually normal sized because membranous ossification is unaffected) with short limbs (from impaired endonchondral ossification)
Are most achondroplasia mutations hereditary or sporadic?
Sporadic
What other condition can achondroplasia cause?
Dwarfism
How does achondroplasia affect life span, fertility, and mental function?
They are all normal
How is osteoporosis diagnosed?
Bone mineral density test (DEXA) with a T score of < -2.5
Long term use of what medication can lead to osteoporosis?
Steroids
What happens in osteoporosis?
Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization
What is a major complication of osteoporosis?
Vertebral crush fractures - acute back pain, loss of heigh, kyphosis
What are the 2 types of osteoporosis?
Type 1 - postmenopausal
Type 2 - senile
Senile osteoporosis typically affects men and women greater than what age?
70
Why are postmenopausal women at increased risk of osteoporosis?
Decreased estrogen levels
What 2 fractures are common in postmenopausal women with osteoporosis?
- Femoral neck
2. Distal radius (Colles)
Describe different prophylaxis treatments for senile osteoporosis.
- Regular weight-bearing exercise
2. Adequate calcium and vitamin D intake throughout adulthood
How can we treat senile osteoporosis?
Bisphosphonates, PTH, SERMs, rarely calcitonin, denosumab (monoclonal antibody against RANKL)
What is another name for osteopetrosis?
Marble bone disease
Which cells are defective in osteopetrosis?
Osteoclasts
Describe the bones in osteopetrosis.
Thickened and dense but prone to fracture
Why do we see pancytopenia and extramedullary hematopoiesis in osteopetrosis?
Bone fills the marrow space
What is the cure for osteopetrosis?
Bone marrow transplant - osteoclasts are derived from monocytes so allows the patient to make normal monocytes/osteoclasts
What is the classic mutation in osteopetrosis and how does that lead to the disease?
Mutation in carbonic anhydrase II impairs the formation of an acidic environment which is necessary for bone resorption so the osteoclast is inhibited in its activity
Why does osteopetrosis sometimes present with vision and hearing impairment?
Cranial nerve impingement and palsies as a result of narrowed foramina
How does the mutation in osteopetrosis affect the kidney?
Can lead to renal tubular acidosis (impairment of carbonic anhydrase II)
What is the major deficiency in osteomalacia/rickets?
Vitamin D
Does osteomalacia/rickets occur in kids/adults?
Rickets - children
Osteomalacia - adults
Describe the pathogenesis of osteomalacia/rickets.
Vitamin D deficiency –> defective mineralization/calcification of osteoid –> soft bones that bow out (rickets) or weak bones that fracture (osteomalacia)
Describe the lab values of vitamin D, calcium, PTH, serum phosphate, and ALP in osteomalacia/rickets.
Decreased: vitamin D, calcium, phosphate
Increased: PTH, ALP
How does ALP affect osteoblastic/osteoclastic activity?
Promotes osteoblastic activity by forming an alkaline environment
What bone disease has an increase in both osteoblastic and osteoclastic activity?
Paget disease of bone
What is another name for Paget disease of bone?
Osteitis deformans
Describe the serum levels of Ca, phosphorus, and PTH in Paget disease of bone.
Normal
What are the 4 stages in Paget disease?
- Lytic - osteoclasts
- Mixed - osteoclasts + osteoblasts
- Sclerotic - osteoblasts
- Quiescent - minimal osteoclast/osteoblast activity
What are 2 complications of Paget disease of bone?
- High-output heart failure
2. Progression to osteogenic sarcoma
What does Paget disease of bone look like on H&E stain?
Mosaic pattern of woven and lamellar bone
Is Paget disease of bone localized or more systemic?
Localized
What are some common symptoms of Paget disease of bone?
Bone pain, increased hat size, lion-like face, hearing loss (from auditory foramen narrowing)
What is avascular necrosis?
Ischemic damage leading to infarction of bone and marrow
What is another name for avascular necrosis?
Osteonecrosis
What are 5 causes of osteonecrosis?
Trauma, Caisson disease, high-dose corticosteroids, alcoholism, sickle cell
What is the most common site of osteonecrosis?
Femoral head (due to insufficiency of medial circumflex femoral artery)
What are the abnormal lab values in osteoporosis?
None - serum Ca, PO4, ALP, PTH are all normal
What serum lab value might be abnormal in osteopetrosis?
Decreased calcium in severe, malignant disease
What serum lab value is abnormal in Paget disease?
Increased ALP
What are the lab values for serum Ca, PO4, ALP, and PTH in hypervitaminosis D?
Decreased: PTH
Increased: Ca, PO4
Unchanged: ALP
What are two causes of hypervitaminosis D?
- Over-supplementation
2. Granulomatous disease (e.g. sarcoidosis)
What is the major endocrine problem in osteitis fibrosa cystica?
Hyperparathyroidism
What causes “brown tumors” in osteitis fibrosa cystica?
Fibrous replacement of bone, subperiosteal thinning
When do we typically see osteitis fibrosa cystica?
Compensation for end stage renal disease
