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 Jaw osteonecrosis Atypical subtrochanteric and femoral stress fractures Radiographic changes consistent with osteopetrosis