Osteoporosis and Osteopenia

What is it?

Risk factors?

Osteopenia (mild form of osteoporosis)

Characterized as:

• Reduced bone mass
• Reduced bone mineral density
• Reduced bone quality

Results in increase risk fo Fractures or Falls:

• usually in femur, vertebra, hip

Risk Factors:

• Old age: BMD ~ 0.5% annually after age 30
• Low dietary calcium intake
• Post-menopaussal women: BMD decrease 2-5% annually

bone is constantly being TURNOVER under two processes called Bone Resorption and Bone Formation. Its a continous, coupled process!!

Remodling Process:

• Resorption: Osteoclasts move along the surface and will create a space called "Remolding Space" where it basically digest the surface of bone
  • it releases enzymes and acids to digest
  • Bone release calcium, phosphate, cytokines to blood stream
• Formation: Osteoblast attracted to released cytokines, comes along and lay down new bone matrix (collagen with hydroxyapatite crytals)

Prevention and Treatment of Osteoporosis

Goal?

treatment Options?

Goal: prevent bone fracture

• by decreasing osteoclast activity
  • Anti-resorptive drugs
•  by increasing osteoblast activity

Anti-Resorptive Drugs

What are they?

What do they do?

These agents will inrease BMD and reduce fractures by reducing osteoclast activity

•  Reduces bone resorption within wks and bone formation is reduced within months
• remolding spaces fills in and bone hardens

Types of options:

• Bisphosphonates
• Calcitonin
• Calcium
• Estrogen
• Raloxifene
• Vit D

*Both are hormone therapy

Estrogen:

• only for prevention, not treatment
• reduce fracture by 50%

Evista (Raloxifene):"SERM"

• Rx for prevention and treatment  
• increases BMD
• reduces fractures
  • Less efficaciuos than Estrogen bc

    •  
      • Recall that estrogen has a number of effects, but Evista is able to avoid some of those adverse effects.
      • What we give up as terms of adverse effects by using Evista , we also give up a little bit in terms of efficiency.

Bisphosphonates for Treatment of Osteoporosis

MOA?

• most commonly used
• MOA: they bind to calicum in the bloodstream
  • drug-bound to calcium will get incorporated into bone
  • then osteoclast comes and digest the matrix
  • so now the bisphosphonate is in the osteoclasts now and this causes, APOPTOSIS
  • osteoclasts dies
  • results in reduction of bone resorption

Bisphosphonates

Drugs?

Indication?

ADR?

Administration?

Indication: Prevention and Treatment of Osteoporosis

* it is as efficacious as estrogen

• Alendronate (Fosamax)
  • taken weekly
• Risedronate (Actonel)
  • taken weekly
• Ibandronate (Boniva)
  • taken monthly
  • associated with myalgia, joint aches, fever

Administration:

-these are poorly absorped, take on empty stomach

-swallow whole, with 8oz glass of water and remain upright

-binds to calcium so dont take with milk

ADR:

-myalgia

-erosive esophagitis (GERD increase this risk)

Calcitonin

What is it?

Indication?

Treatment of Osteoporosis

• Peptide hormone secreted by thyroid cells in response to high calcium
• Activation of calcitonin receptor on osteoclasts inhibits osteoclast activity
• Activation of calcitonin receptor in kidney reduces reabsorption of calcium, increases excretion
  • Net result is reduced plasma calcium

Parathyriod Hormone (PTH)

What is it?

how can it cause osteoporosis?

Forteo®

What is it?

Uses?

Effects?

"its an anabolic agent"

• it is recombinant human PTH "rhPTH(1-34)
• Rx for moderate -severe osteoporosis
• MOA: it is different from endogenous PTH
  • at low, intermittent, daily doses, it increases osteoblast!!
•  Increase bone formation
• VERY EFFICACIOUS!!!!
  • there is no plateau of effects like the Anti-resorptive where after a while they dont work anymore

Forteo®

Administration?

ADR?

• Administration: SQ INJ daily
• ADR:
  • mild hypercalcemia
    • may inc digoxin toxicity
  •  orthostatic HYPOTN
    • w/in hours of first few doses
  •  hyperuricemia
  • inc risk of osteosarcoma
    • dose & duration dependent
    • duration limited to 2 yrs