This document discusses osteoporosis, its pathogenesis, current treatment options, and potential future therapies. It describes how osteoporosis results from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Current treatments either inhibit osteoclastic activity to decrease bone resorption or stimulate osteoblastic activity to increase bone formation. First-line therapies are bisphosphonates and calcitonin, while PTH is used for high-risk patients. Emerging drugs combine anti-resorptive and anabolic mechanisms or target new pathways like sclerostin inhibition. Future therapies aim to have better safety profiles and reliable biomarkers for prevention.

1. THE TREATMENT OF OSTEOPOROSIS
Vincent Chang

2. Osteoporosis = porous bone
Most commonly affected are the
bones of the spine, hip, and wrist.

3. Osteoporosis Pathogenesis
- Bone is constantly renewing itself
- Old bone tissue is broken down by cells called osteoclasts and
replaced by new bone material produced by cells called osteoblasts.
- The balance

4. Morbidity and Mortality
"dowager's hump."

5. Therapeutic options for osteoporosis
MoA:
Inhibit osteoclastic activity, decrease bone reabsorption
or
Stimulate osteoblastic activity, increase bone formation
1.
Drugs preventing resorption
(Anti-resorptive treatment)
2. Drugs Stimulating new bone formation
(Anabolic therapy)

6. 1.Drugs preventing resorption (Anti-resorptive)
Bisphosphonates
• First line therapy
– Alendronate
– Etidronate
– Risedronate
– Ibandronate
– Zelodronate – new, administrated once per year
Calcitonin
– Miacalcic
Selective estrogen receptor modulators (SERMs)
• Second line therapy – for patients do not tolerate bisphosphonates
– Raloxifene (2nd Gen)
– Bazedoxifene (3rd Gen, Recently approved in EU)

7. 2. Drugs Stimulating new bone formation
(Anabolic Therapy)
Recombinant Parathyroid hormone (PTH)
• significantly more expensive than Bisphosphonates
• reserve for high risk fracture patient
– Teriparatide- the latest in the series and the most promising
results.
– Preotact

8. Emerging drugs that combine 1+2
• Strontium ranelate i
– 37% decrease risk of vertebral fracture in treated population on
2g strontium ranelate for 3 years
• Amgen’s new mAb – denosumab (FDA approved June 2010)
RANFL Osteoclast Bone destruction
• Cathepsin K inhibitor - Cathepsin K produced by activated
osteoclast
– Odanacatib (Phase III Trial)
Other potential new drug:
• CIC 7 Inhibitor
• Wnt-ß-catenin pathway targets:
sclerostin, DKK1 antagonists, lithium.

9. The Future
Drawback of First line therapy
Small molecule drugs or mAb
• Better safety profile
– less side effects
• Reliable biomarker for
prevention
Typical Atypical fracture
osteoporosis after many years
fracture bisphosphonate
therapy.

10. Q?