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Updated: Jun 22 2021


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  • Overview
    • Overview
      • class of drugs that prevent bone mass loss by inhibiting osteoclast resorption
        • prevent formation of osteoclast ruffled borders microtubules, causing apoptosis
        • inhibition of osteoclasts also infereres with normal bone healing and remodeling
      • there are two types of bisphosphonates
        • non-nitrogen containing
          • tiludronate
          • clodronate
          • etidronate
        • nitrogen containing
          • alendronate
          • risedronate
          • pamidronate
          • zolendronate
            • zoledronic acid - relatively new and appealing to patients, due to IV adminstration every 12 months
  • Indications
    • Indications
      • osteoporosis
        • can resume 1-week postop from osteoporotic hip fracture surgery
      • metastatic bone disease
      • multiple myeloma
      • paget's disease
      • polyostotic fibrous dysplasia
      • total joint arthroplasty to prevent osteolysis
      • early stage avascular necrosis
      • osteogenesis imperfecta
      • metastatic hypercalcemia
  • Contraindications
    • Contraindications
      • severe renal disease
        • primary mode of excretion is renal
      • following lumbar fusion
        • decreased spinal fusion rates in lab animal models (increased fusion mass size, but decreases the actual fusion rate)
  • Mechanism
    • Delivery
      • bisphophonates accumulate in high concentration in bone due to binding affinity to calcium
      • bisphosphonates are ingested by osteoclasts and work by two different methods depending on presence of nitrogen atom on the alkyl chain
    • Nitrogen containing bisphosphonates mechanism
      • inhibits osteoclast farnesyl pyrophosphate synthase enzyme, required in mevalonate (cholesterol pathway)
        • inhibits GTPase formation
    • Non-nitrogen containing bisphosphonates (simple) mechanism
      • induce osteoclasts to undergo premature death and apoptosis
        • does so by forming a toxic adenosine triphosphate (ATP) analogue
  • Treatment
    • Vertebral Compression Fractures
      • indications
        • vertebral compression fracture in osteoporotic patient
          • bone mineral density 2.5 or more standard deviations below that of young healthy adults (T score < 2.5 SD)
      • outcomes
        • 1 year of treatment with a pharmacologic antiosteoporotic medication, the risk of vertebral fracture decreases by 50-60%
    • Non-vertebral Fragility fractures
      • indications
        • fragility fracture in osteoporotic patient
      • outcomes
        • effective in reducing the risk of multiple fractures
    • Osteogenesis imperfecta
      • cyclical IV pamidronate administration
        • reduces bone pain and fracture incidence
        • increases level of ambulation and bone density
    • Multiple myeloma
      • indications
        • diagnosis of multiple myeloma
      • outcomes
        • reduced incidence of skeletal events in multiple myeloma
    • Avascular necrosis
      • indications
        • early, precollapse AVN
      • outcomes
        • still considered investigational
        • randomized clinical trial showed that bisphosphonate treatment was more effective at preventing head collapse than placebo at 2 years (bisphosphonate collapse 6.9% vs placebo collapse 76%)
  • Side Effects & Complications
    • Radiographic changes consistent with osteopetrosis
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