Osteoporosis, Osteomalacia and Paget's Disease Flashcards
What is the main function of cortical bone?
Mechanical and protective function
Always on outside and surrounds trabecular bone
What is the main function of trabecular bone?
Metabolic function
~20% of bone
What type of bone is more actively remodeled?
Trabecular bone
What is the temporal different in bone resorption versus bone formation?
Bone resorption is relatively rapid (requires about 2 weeks)
Bone formation is slow, requiring 4-6 months
What kind of bone has a higher turnover rate?
Trabecular or cancellous – higher surface to volume ratio
Cortical or compact bone has a lower turnover rate, less vascularity
What gives bone its compressive strength? What about its tensile strength?
Compressive - mineral
Tensile-protein
What is the primary protein of bone’s extracellular matrix?
Type 1 collagen
What types of cracks are less able to propagate?
Transverse cracks to cement lines
What is the dual physiology of bone?
Mechanical physiology - loading and unloading
Mineral physiology - Ca balance, phosphate balance
What is thought to play a role in decreased bone density in older adults?
Decreased sensitivity to mechanical loading
How should we look at osteoporosis?
Instead of thinking of it as patients suffering from low bone mineral density (BMD), consider osteoporosis as a risk factor for fractures
How does WHO define osteoporosis?
Skeletal disorder categorized by compromised bone strength predisposing to an increased risk of fracture
What two main features reflect the integration of bone strength?
Bone density (easily measured) Bone quality (not as easily measured)
How is osteoporosis established on a DEXA scan?
T-score >-2.5 in a postmenopausal women or man over 50
*but not all >-2.5 should be diagnosed with osteoporosis
How are long bones loaded?
By bending - tension on one side and compression on the other
How are vertebrae loaded?
Primarily in compression and torsion
What does BMD correlated with?
Compressive strength but doesn’t give any information about tensile strength
What is the single most powerful predictor of future fractures?
Past fractures
How does sex contribute to risk?
Lifetime fracture risk for women is 50%
For men it is 25-30%
What is responsible for this differences in the sexes of fracture percentage?
Male bones grow larger
Female bones go through rapid bone loss peirimenopausally
Female loss in trabecular bone tens to be patchier than in males – impact on strength
What are some other risk factors for increased hip fractures?
Age
Use of glucocorticoids at doses >7.5 mg
What are the two best fracture risk calculators?
FRAX
Garvan
What is another differential when thinking about osteoporosis?
Osteomalacia
What leads to osteomalacia?
If the mineral components of bone matrix are not present in sufficient quantity then the matrix will be under mineralized and weak.
What test shows if osteomalacia is present?
Dynamic histomorphometry
Use tetracycline
Normal bone – have 2 sharp lines that mark the mineralization front
Osteomalacia – have a smudge and increased ostend volume
What are some common lab findings in osteomalacia?
Elevated PTH (secondary)
Elevated Alk phos
Elevated P1NP
Is it possible for a person to have both osteomalacia and osteoporosis?
Yes
Drugs that work by limiting the initiation of new bone remodeling units
Antiresorptives - bone formation takes longer than bone resorption, inhibiting the process of remodeling allows the remodeling space to be filled –> reduction in fracture risk and increase in BMD
What percent of CaCO3 is elemental calcium?
40%
What percent of Ca citrate is elemental calcium?
21%
Estrogens and selective estrogen receptor modulators
Tamoxifen
Raloxifene
Prevent increased remodeling that occurs after menopause
Bisphosphonates
Oral - Alendronate, Risedronate
IV - Pamidronate, Zoledronic acid
Mechanism of bisphosphonates
Resemble pyrophosphate but oxygen replaced by carbon
Inhibit conversion of mevalonate to farnesyl, interfere with protein modification in osteoclasts, leading to apoptosis
Injected decoy for RANKL
Binds to RANKL, making it unable to bind endogenous receptor RANK and interrupts RANKL-RANK signaling preventing osteoclast differentiation
Denosumab
Synthetic produced fragment of PTH
When given episodically exerts an anabolic effect and increases bone mass
Teriparatide
What is the storage form of vitamin D?
25-OH vitamin D - 25-hydroxylated in the liver
What is the active form of vitamin D?
1, 25-OH vitamin D
1-hydroxylated in the kidney
Has direct effects on the intestinal epithelium to increase Ca and phosphate absorption and on bone to increase remodeling
What are some things that may cause secondary hyperparathyroidism?
Nutritional deficiency
Renal disease leading to impaired vitamin D activation
GI disease leading to malabsorption
Use of medications that accelerate vitamin D clearance (anti-epileptic drugs)
What is the role of FGF23?
Key regulator of phosphate homeostasis, acting as a phosphaturic hormone
Inhibits the expression of 1-hydroxylase, reducing vitamin D activation
What are some examples of hypophosphatemic disorders?
Tumor induced osteomalacia
Autosomal dominant hypophosphatemic rickets
Autosomal recessive hypophosphatemic rickets
X-linked hypophosphatemic rickets
All include elevated levels of FGF23, hypophosphatemia and osteomalacia
How does osteomalacia present during growth?
Rickets
What is Paget’s Disease?
Foci of exerverant, unregulated bone turnover
- Woven bone
- Increased vascularity
- Bone deformity - bowing, osteitis deforming
