Metabolic Bone Disease Flashcards
Bone remodeling
- osteoclasts: make resorption pits using enz/acid
- osteoblasts: fill pit back up with osteoid (bone specific collagen, high affinity for Ca phosphate crystal): calcifying osteoid: Ca x PO4 greater than 24
Osteoclasts have RANK, which binds RANK-L
lots of RANK L and not much OPG: bone resorption high (high OPG bone resorption low)
Sclerostin
prevents new bone formations
Promotion of osteoblasts (signaling)
Wnt
Frizzled/LRP5
B-catening
Osteoporosis
compromised bone strength, increased risk of fragility fractures
Types of fragility fractures and RFs
spine, most (only 1/3 cause pain)
hip
wrist
fragility fractures= osteoporosis
RFs: age falls low bone mass previous fractures
T score
SDs below peak bone mass
- 1-2.5 below peak bone mass: osteopenia
- 2.5 and further below: osteoporosis
abnormal bone remodeling
increased resorption or decreased formation: bone mass lost
Non modifiable RFs fro low bone mass
Age Race Gender Family History Early Menopause
Modifiable
Low Calcium Intake Low Vitamin D Intake Estrogen Deficiency Sedentary Lifestyle Cigarette Smoking Excess Alcohol (greater than 2/day) Excess Caffeine (greater than 2/day) Medications: Glucocorticoids, Excess Thyroid Hormone, Anticonvulsants Probable/Possible: Thiazolidinediones, SGLT2-I’s, SSRI’s, PPI’s
Osteoporosis Prevention and Tx
1000-1500 mg Ca/d
Vit D: 1000units/d
exercise: aerobic, resistance
falls: assess/prevent
Osteomalacia and rickets
impaired bone mineralization resulting in soft, weak bones
Osteomalacia: adults
rickets: kids
*inadequate ca x phosphate product for bone mineralization (should be above 24)
Phosphate disorders
Acquired Hypophosphatemia
Poor Oral Intake
Renal Phosphate Wasting
Congenital Hypophosphatemic Rickets
“Vitamin D Resistant Rickets”
Renal Phosphate Wasting
Impaired 1,25 (OH)2 Vitamin D Formation
Osteomalacia features, and readiology
pain
deformities
fractures
Radiology:
fractures
pseudofractures (Milkman’s Fractures; Looser’s Lines)
Rickets features and radiology
pain
deformities
muscle weakness
short stature
Radiology
bowing of long bones
flaring ends of long bones
-delayed epiphyseal calcification
Paget’s Disease of Bone
-an idiopathic bone condition characterized by excessive/unregulated bone resorption and formation
- genetic (familial aggregation; 18q linkage; mutation of osteoprotegerin gene; mut of sequestosome 1/P62 gene)
- chronic paramyxovirus infection
- viral disorder evidence (geographic variation; dog ownership; time trends; viral studies)
Sequestosome I
SQSTMI: ubiquitin binding protein. Forms ubiquitinated chains that function as protein scaffolds for IL-1 and TNF induced NF-kB activation, which regulates RANK signaling that controls osteoclast differentiation, activity and survival.
SQSTMI mutations: linked to Paget’s Disease
clinical features of Paget’s disease
Skeletal: Pain Deformity Fractures Osteoarthritis Hypervascularity Acetabular Protrusion Osteogenic Sarcoma
Neuro:
deafness (8th n, ossicles)
CN compression (bony)
spinal cord compression (vascular)
CV:
atherosclerosis
aortic stenosis
CHF (high output)
Common sites of involvement: pelvis skull vert femur tibia
Paget’s progression
1st 10 yrs: osteoclastic (increase NTX/CTX)
Then: osteoclastic/osteoblastic mixed phase (high NTX/CTX); alk phos high
After 20 years: osteoblastic (NTX/CTX low) alk phos high or low
Dx of Paget’s disease
remodeling markers: elevated
XR feat: very specific
(osteolytic lesions: blades of grass on long bones and resorption frot in flat bones; osteosclerotic lesions; thickened disorg trabeculae; thick, expanded cortex; expansion of bone size)
bone scan: very sensitive (intense uptake in osteoblastic stage)
bone biopsy: occasionally needed
Histology of Paget’s
Increased Osteoclast Numbers
Increased Osteoclast Nuclei (20-100 per cell)
Increased Osteoblasts in Periphery
Disorganized, Mosaic, Woven Bone
