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How does estrogen provide its protective bone effects?
Stimulates 1-alpha hydroxylase activity in kidney and positive effect on intestinal Ca absorption
Classic bone fractures in osteoporosis.
Vertebral (mostly asyx; kyphosis--hunchback)
Hip (require surgical intervention)
Wrist
How would you interpret a T score for a bone density scan?
T > -1: Normal

-2.5<T<-1: Osteopenia (more than 1 and less than 2.5 SDs below mean in young adults of same sex and race)

Not really applicable for 10 year olds unless you compare to 10 year olds

T<-2.5: Osteoporosis (more than 2.5 SDs below mean in young adults of same sex and race; skeletal fragility)
What does bone density interpretation help predict?
Fracture risk

Low bone density-->increased rate of fractures
Effect of age on calcium absorption.
Inc'd age-->resistance to active 1,25 D
Vit D levels tend to be lower (need to give higher doses)
About how much calcium do you need a day to maintain bone health?
1000-1200 mg

(look at calcium component on supplements, not just mg of calcium carbonate)
Is calcium supplementation sufficient in postmenopausal women?
NO, it will help, but lack of estrogen will outweigh supplements.

Need something else.
25-OH D levels below _____ stimulate PTH release.
Below 30

(Normal is 10-50)
Recommendation of Vit D per day.
800-1000 IU qd
Adverse reactions of vitamin D.
Toxicity not associated with sun exposure (need really high oral intake like 25K-60K IU qd x 1-4mos)

Usually hypercal
What warrants a bone mineral density test?
-Fragility Fracture
-Men >70
-Postmenopausal women >65
-Postmenopausal women <65 with risk factors
-Premenopausal women and men w/2º cause
What is a fragility fracture?
Fall from standing height
(low impact)
What's a FRAX calculation?

How does it help determine who receives pharmacologic therapy?
Calculates 10 year risk of a fracture based on risk fractures

If risk >20% for major fracture, if hip fracture risk >3%, need pharmacotherapy! APPLICABLE TO OSTEOPENIC PTS

ALL OSTEOPOROTIC pts need pharmacotx
Estrogen replacement therapy reduces the rate of _____ but also increases the rate of ______.
Reduces rate of fractures, but increase rate of CHF and stroke

No longer first-line tx
Raloxifene:
Drug Class
Effects
Selective Estrogen Receptor Modulator.
Raloxifene (only SERM approved for osteoporosis):
Improves bone density
Decreases LDL
Possible DVT association
Tamoxifen:
Drug Class
Effects
Selective Estrogen Receptor Modulator
Improves Bone Density
Increases HDL
Decreases LDL
Stimulates endometrium (possible risk for cancer; use for only 5 years in pts w/BrCa)
Assocn with DVT
Calcitonin:
Produced by
Stimulated by
Effects
Parafollic cells of thyroid

Antagonist to PTH

Stimulated by high Ca levels to inhibit osteoclast formation
Increases renal Ca excretion by decreasing tubular reabsorption

Can be used in osteoporosis (antagonize PTH-->less bone resorption)
Bisphosphonates:
Mechanism
Suffix
AE's
-dronate
(Alendronate is first line bc it's generic)

Prevent osteoclast binding to bone
Reduce spine and hip fractures

Take once a month and can't lie down so doesn't crawl back up esophagus

AE:
MSK pain
Gi syx
Hypocalcemia
Atrial Fibrillation
Osteonecrosis of jaw
Why is Recombinant PTH used as a treatment for osteoporosis?

Side Effects?
Intermittent PTH (given daily) stimulates bone formation more than resorption and builds bone

AE:
Osteosarcoma (used for 2 years max; don't give to young people or those at risk for bone cancer)
Denosumab:
Mechanism
AE's
Osteoclasts have RANK
Osteoblasts have RANK-L

Denosumab is anti-RANK-ligand so osteoblasts can't bind osteoclasts to activate them

Risk for skin infections
What therapies are ineffective against preventing nonvertebral and hip fractures?
Ibandronate (Boniva)
Raloxifene
Calcitonin