Osteoporosis = porous boneMost commonly affected are thebones of the spine, hip, and wrist.
Osteoporosis Pathogenesis- Bone is constantly renewing itself- Old bone tissue is broken down by cells called osteoclasts andreplaced by new bone material produced by cells called osteoblasts.- The balance
Therapeutic options for osteoporosisMoA:Inhibit osteoclastic activity, decrease bone reabsorption orStimulate osteoblastic activity, increase bone formation 1. Drugs preventing resorption (Anti-resorptive treatment) 2. Drugs Stimulating new bone formation (Anabolic therapy)
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)
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
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.
The FutureDrawback 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.