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 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ13.147) It is recommended that invasive dental work be completed prior to the initiation of which of the following medications? Tested Concept QID: 4782 Type & Select Correct Answer 1 Glucosamine 0% (16/3661) 2 Cholecalciferol 1% (37/3661) 3 Levothyroxine 1% (22/3661) 4 Teriparatide 16% (583/3661) 5 Bisphosphonates 81% (2977/3661) L 2 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept (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? Tested Concept QID: 3650 FIGURES: A B Type & Select Correct Answer 1 Long-term corticosteroid use 2% (51/2377) 2 Secondary malignancy arising from Paget disease 1% (31/2377) 3 Long-term alendronate use 95% (2261/2377) 4 Long-term ergocalciferol use 0% (11/2377) 5 Short-term teraparatide use 0% (10/2377) L 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review tested concept Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (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? Tested Concept QID: 3443 Type & Select Correct Answer 1 Inhibition of farnesyl diphosphate synthase 29% (883/3078) 2 Conversion of drug into a non-functioning ATP-analogue 54% (1648/3078) 3 Interference of isoprenylation of small GTPases 9% (280/3078) 4 Inhibition of geranylgeranyl diphosphate synthase (GGPPS) 5% (158/3078) 5 Downregulation of the undecaprenyl diphosphate synthase (UPPS) pathway 3% (89/3078) L 3 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review tested concept (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? Tested Concept QID: 3646 FIGURES: A B Type & Select Correct Answer 1 No change in bone pain 3% (23/766) 2 No change in future fracture incidence 5% (37/766) 3 An increase in osteoblast density 11% (85/766) 4 An increased risk of secondary osteosarcoma 8% (64/766) 5 An increase in bone density 72% (551/766) L 2 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept (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? Tested Concept QID: 3462 Type & Select Correct Answer 1 Jaw 3% (126/3622) 2 Lumbar spine 1% (30/3622) 3 Femoral neck 2% (86/3622) 4 Subtrochanteric femur 93% (3353/3622) 5 Anterior cortex of tibia 0% (16/3622) L 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review tested concept Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ10.173) Which of the following agents has been shown to exert its effect by inhibiting protein prenylation and GTPase formation? Tested Concept QID: 3266 Type & Select Correct Answer 1 Selective Cox-2 inhibitors 6% (138/2407) 2 Alendronate 63% (1525/2407) 3 Cholecalciferol 6% (156/2407) 4 Etidronate 20% (472/2407) 5 Indomethacin 4% (103/2407) L 3 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review tested concept (OBQ09.262) What is the primary mode of bisphosphonate excretion? Tested Concept QID: 3075 Type & Select Correct Answer 1 Renal 88% (1470/1674) 2 Gastrointestinal 4% (67/1674) 3 Liver 7% (116/1674) 4 Skin 0% (5/1674) 5 Pulmonary 1% (11/1674) L 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review tested concept (OBQ09.63) Nitrogen containing bisphosphonates inhibit osteoclasts by targeting what enzyme or hormone? Tested Concept QID: 2876 Type & Select Correct Answer 1 HMG-CoA reductase 7% (80/1115) 2 farnesyl diphosphate synthase 80% (895/1115) 3 tissue inhibitor of metalloprotease 3% (38/1115) 4 alkaline phosphatase 6% (68/1115) 5 calcitonin 3% (30/1115) L 2 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Review tested concept Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ08.59) What effect do bisphosphonate medications have on spinal fusion surgery when taken in the postoperative period? Tested Concept QID: 445 Type & Select Correct Answer 1 Any effect can be counteracted by taking calcium supplements 1% (7/1371) 2 No effect 20% (270/1371) 3 Increased risk of wound infection 2% (33/1371) 4 Smaller fusion mass 13% (173/1371) 5 Decreased fusion rate 64% (884/1371) L 3 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept (OBQ08.223) Osteonecrosis of the jaw has been recognized as a possible complication of chronic therapy with which of the following medications? Tested Concept QID: 609 Type & Select Correct Answer 1 Warfarin 2% (12/773) 2 Low-molecular weight heparin 0% (3/773) 3 Diclofenac 2% (14/773) 4 Ketorolac 1% (6/773) 5 Alendronate 95% (734/773) L 1 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ07.134) What medication has been shown to decrease osteolysis after total joint replacement surgery? Tested Concept QID: 795 Type & Select Correct Answer 1 Bisphosphonates 70% (2163/3082) 2 NSAIDs 4% (120/3082) 3 TNF-alpha inhibitors 12% (376/3082) 4 Calcium and vitamin D supplementation 12% (361/3082) 5 BMP-7 2% (48/3082) L 2 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review tested concept (OBQ06.72) Radiographic changes suggestive of osteopetrosis in children are a known complication of which of the following types of medications? Tested Concept QID: 183 Type & Select Correct Answer 1 TNF-alpha inhibitors 3% (39/1157) 2 Bone morphogenic proteins 3% (38/1157) 3 Bisphosphonates 71% (820/1157) 4 Fluoroquinolones 11% (123/1157) 5 RANKL antibiodies 12% (134/1157) L 2 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review tested concept (OBQ06.86) What is the cellular mechanism of action for non-nitrogen containing bisphosphonates (such as clodronate and etidronate) to induce osteoclast apoptosis? Tested Concept QID: 197 Type & Select Correct Answer 1 Inhibiting caspase 3% (32/1186) 2 Inhibiting matrix metalloprotease 8% (93/1186) 3 Inhibiting reverse transcriptase 4% (50/1186) 4 Targeting of farnesyl diphosphate synthase 32% (380/1186) 5 Creating toxic analog of adenosine triphosphate that targets mitochondria 53% (625/1186) L 3 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept (OBQ06.236) What is the mechanism of action of non-nitrogen containing bisphosphonate (e.g. clodronate and etidronate) medications? Tested Concept QID: 247 Type & Select Correct Answer 1 Post-translational carboxylation of vitamin K dependent proteins 1% (9/1395) 2 Decreased osteoblastic acivity 3% (45/1395) 3 Inhibits farnesyl diphosphate synthase in osteoclasts 43% (595/1395) 4 Increased osteoclast apoptosis 52% (724/1395) 5 Increases bone turnover 1% (13/1395) L 3 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 4 Review tested concept (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? Tested Concept QID: 67 Type & Select Correct Answer 1 remain the same 8% (49/600) 2 decrease by 20% 20% (120/600) 3 decrease by 40% 48% (287/600) 4 decrease by 60% 21% (127/600) 5 increase by 10% 2% (11/600) L 4 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Review tested concept (OBQ04.247) Which of the following molecules binds to the surface of hydroxyapatite crystals and prevents protein prenylation? Tested Concept QID: 1352 Type & Select Correct Answer 1 Calcitonin 14% (82/577) 2 Parathyroid Hormone 7% (41/577) 3 Raloxifene 16% (92/577) 4 Calcium 12% (70/577) 5 Alendronate 50% (290/577) L 3 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review tested concept
All Videos (0) Podcasts (2) Question Session⎪Bisphosphonates Orthobullets Team Basic Science - Bisphosphonates Listen Now 15:35 min 11/6/2019 24 plays (1) Basic Science⎪Bisphosphonates Team Orthobullets 4 Basic Science - Bisphosphonates Listen Now 4:58 min 10/15/2019 95 plays (1)
Atypical Femur Fx in 78F (C2587) Benjamin C. Taylor Basic Science - Bisphosphonates E 5/24/2016 8829 58 16