Introduction 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 osteoporosis 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 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
QUESTIONS 1 of 22 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ06.236) What is the mechanism of action of non-nitrogen containing bisphosphonate (e.g. clodronate and etidronate) medications? Review Topic QID: 247 1 Post-translational carboxylation of vitamin K dependent proteins 0% (3/835) 2 Decreased osteoblastic acivity 3% (28/835) 3 Inhibits farnesyl diphosphate synthase in osteoclasts 45% (379/835) 4 Increased osteoclast apoptosis 49% (412/835) 5 Increases bone turnover 1% (8/835) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 4 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ11.227) A 67-year-old female presented 2 months ago to her primary care physician with left sided thigh pain. A radiograph was taken at that time and is shown in Figure A. She was diagnosed at that time with a quadriceps strain and given a prescription for ibuprofen and physical therapy. She is now in the emergency room with severe left thigh pain and inability to bear weight on the left lower extremity after bending down to tie her shoes. She denies any constitutional symptoms. A current radiograph from the emergency room is shown in Figure B. Which of the following most likely explains this patient's fracture? Review Topic QID: 3650 FIGURES: A B 1 Long-term corticosteroid use 2% (31/1840) 2 Secondary malignancy arising from Paget disease 1% (25/1840) 3 Long-term alendronate use 96% (1760/1840) 4 Long-term ergocalciferol use 1% (10/1840) 5 Short-term teraparatide use 0% (5/1840) ML 1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ04.247) Which of the following molecules binds to the surface of hydroxyapatite crystals and prevents protein prenylation? Review Topic QID: 1352 1 Calcitonin 15% (63/427) 2 Parathyroid Hormone 7% (29/427) 3 Raloxifene 16% (67/427) 4 Calcium 13% (56/427) 5 Alendronate 50% (212/427) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ06.72) Radiographic changes suggestive of osteopetrosis in children are a known complication of which of the following types of medications? Review Topic QID: 183 1 TNF-alpha inhibitors 3% (30/997) 2 Bone morphogenic proteins 3% (31/997) 3 Bisphosphonates 72% (722/997) 4 Fluoroquinolones 11% (107/997) 5 RANKL antibiodies 11% (106/997) ML 2 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (OBQ06.86) What is the cellular mechanism of action for non-nitrogen containing bisphosphonates (such as clodronate and etidronate) to induce osteoclast apoptosis? Review Topic QID: 197 1 Inhibiting caspase 2% (26/1075) 2 Inhibiting matrix metalloprotease 8% (86/1075) 3 Inhibiting reverse transcriptase 4% (46/1075) 4 Targeting of farnesyl diphosphate synthase 31% (334/1075) 5 Creating toxic analog of adenosine triphosphate that targets mitochondria 54% (579/1075) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ08.59) What effect do bisphosphonate medications have on spinal fusion surgery when taken in the postoperative period? Review Topic QID: 445 1 Any effect can be counteracted by taking calcium supplements 0% (2/1043) 2 No effect 19% (200/1043) 3 Increased risk of wound infection 2% (23/1043) 4 Smaller fusion mass 13% (139/1043) 5 Decreased fusion rate 65% (676/1043) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ10.173) Which of the following agents has been shown to exert its effect by inhibiting protein prenylation and GTPase formation? Review Topic QID: 3266 1 Selective Cox-2 inhibitors 6% (121/2136) 2 Alendronate 64% (1360/2136) 3 Cholecalciferol 7% (142/2136) 4 Etidronate 20% (418/2136) 5 Indomethacin 4% (87/2136) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (OBQ11.20) A 62-year-old woman with Paget’s disease is started on a non-nitrogen containing bisphosphonate for treatment of her condition. What is the mechanism of action of this drug? Review Topic QID: 3443 1 Inhibition of farnesyl diphosphate synthase 29% (757/2615) 2 Conversion of drug into a non-functioning ATP-analogue 53% (1390/2615) 3 Interference of isoprenylation of small GTPases 9% (242/2615) 4 Inhibition of geranylgeranyl diphosphate synthase (GGPPS) 5% (134/2615) 5 Downregulation of the undecaprenyl diphosphate synthase (UPPS) pathway 3% (75/2615) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (OBQ11.223) A 10-year-old child falls from a standing height and sustains the injury shown in Figure A. Her medical history includes hearing defects and the facial appearance shown in Figure B. In addition to operative fixation of her fracture she is scheduled to receive cyclical intravenous pamidronate administration as a treatment after the fracture is healed. Which of the following is associated with this form of treatment? Review Topic QID: 3646 FIGURES: A B 1 No change in bone pain 4% (20/540) 2 No change in future fracture incidence 5% (26/540) 3 An increase in osteoblast density 10% (56/540) 4 An increased risk of secondary osteosarcoma 7% (40/540) 5 An increase in bone density 73% (395/540) ML 2 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ11.39) Longterm bisphosphonate usage has been shown to cause an increased risk of stress reaction leading to fracture at which of the following areas? Review Topic QID: 3462 1 Jaw 3% (107/3181) 2 Lumbar spine 1% (24/3181) 3 Femoral neck 2% (68/3181) 4 Subtrochanteric femur 93% (2957/3181) 5 Anterior cortex of tibia 0% (15/3181) ML 1 Select Answer to see Preferred Response PREFERRED RESPONSE 4 (OBQ09.262) What is the primary mode of bisphosphonate excretion? Review Topic QID: 3075 1 Renal 88% (1287/1463) 2 Gastrointestinal 4% (59/1463) 3 Liver 7% (99/1463) 4 Skin 0% (5/1463) 5 Pulmonary 1% (10/1463) ML 1 Select Answer to see Preferred Response PREFERRED RESPONSE 1 (OBQ08.223) Osteonecrosis of the jaw has been recognized as a possible complication of chronic therapy with which of the following medications? Review Topic QID: 609 1 Warfarin 2% (10/590) 2 Low-molecular weight heparin 1% (3/590) 3 Diclofenac 2% (13/590) 4 Ketorolac 1% (6/590) 5 Alendronate 94% (555/590) ML 1 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ09.63) Nitrogen containing bisphosphonates inhibit osteoclasts by targeting what enzyme or hormone? Review Topic QID: 2876 1 HMG-CoA reductase 7% (62/914) 2 farnesyl diphosphate synthase 82% (749/914) 3 tissue inhibitor of metalloprotease 2% (21/914) 4 alkaline phosphatase 6% (57/914) 5 calcitonin 3% (23/914) ML 2 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (OBQ05.30) An 85-year-old patient diagnosed with osteoporosis is begun on a bisphosphonate. What can you tell her about her risk of vertebral fracture after 3 years of treatment? Review Topic QID: 67 1 remain the same 8% (39/469) 2 decrease by 20% 20% (93/469) 3 decrease by 40% 50% (236/469) 4 decrease by 60% 19% (90/469) 5 increase by 10% 2% (8/469) ML 4 Select Answer to see Preferred Response PREFERRED RESPONSE 3 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK
Atypical Femur Fx associated with Bisphosphonates (C2587) Basic Science - Bisphosphonates HPI - Right hip pain x 4 weeks, worsened by ambulation Do you agree this right hip fx is an atypical femur stress fracture associated with prolonged use of bisphosphonates? 5/24/2016 7994 57 16