Atypical Femur Fx Update. Faculty Disclosures

Transcription

1 Atypical Femur Fx Update Rick MD Faculty Disclosures Amgen Speaker Merck Speaker BioClinica Consultant. 2 The World Health Organization considers osteoporosis to be second only to cardiovascular diseases as a critical health problem, due to the high prevalence, costs and effect on quality of life caused by osteoporotic fractures 1

2 In the 30 seconds it took to go over that last slide 10 new osteoporosis-related fractures occurred in the world. Take that in every 3 seconds a new osteoporosis-related fracture occurs Yes my talk is on the risk of AFF but don t forget that 162 fractures are prevented with bisphosphonate treatment for every 1 AFF Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2016;31:16e35. What I ll Teach You What is an Atypical Femur Fx (AFF) The classic associations/causes of an AFF The radiographic finding of an AFF The incidence of AFF The treatment of an AFF What you should tell your patients about anti-osteoporosis meds, Drug Holidays, and risk 2

3 If we have time at the end Latest research on Drug Holidays Latest work on fracture prevention programs Future of Osteoporosis/Fracture Prevention Typical vs. Atypical Fracture 3

4 4

5 Revised ASBMR Case Definition (Excludes High Trauma, Peri-prosthetic and Pathologic Fractures) Revised ASBMR Case Definition (Excludes High Trauma, Peri-prosthetic and Pathologic Fractures) 5

6 New Major Criterion: Localized lateral cortex periosteal reaction Represents callus formation around a developing stress fracture All the participants agree that this seems to be a very specific feature of atypia and one that many investigators use to define atypical fractures This is also corroborated by the work of Feldstein and also of Aspenberg ASBMR Task Force AFF Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) have been reported in patients taking BPs, and in patients on denosumab Also occur in patients with no exposure to these drugs ASBMR Task Force AFF The association with specific diseases and drug exposures was removed from the minor features These associations should be sought rather than included in the case definition The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fx site was changed from a minor to a major feature 6

7 14 months ago 3 months ago 7

8 Bisphosphonates similar structure to calcium hydroxyapatite molecule Mechanism killer of osteoclast! Bisphosphonates work by killing or seriously interfering with osteoclast. They are just one of several anti-resorptive agents Long lasting in bone - years or even decades 8

9 Warning of potential problems Dr Ott warned of potential theoretical complications of interfering with remodeling ever since the year 2000 For the most part we didn t take these warnings seriously until

10 The Dreaded Black Line 10

11 11

12 DBL - Dreaded Black Line 12

13 Summary KP SCAL ,835, years old 188,814 on Bisphosphonates (BP) 10% 142 pts with AFF -128 on BP (90%) Average age 69.3 ± 8.6 years Only 5 men 70 Asians (49.3%), 1 Black (0.7%), 12 Hispanics (8.5%), and 59 Whites (41.5%) 22.5% bilateral AFF 13

14 per 100, Santa Fe Bone Symposium Proportion of bisphosphonate-exposed patients with atypical fracture Duration of bisphosphonate use, years The odds ratio of developing an atypical femoral fracture range from Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma May-Jun;22(5): Feldstein AC, Black D, Perrin N, Rosales AG, Friess D, Boardman D, R, Santora A, Chandler JM, Rix MM, Orwoll E. Incidence and demography of femur fractures with and without atypical features. J Bone Miner Res May;27(5): Schilcher J, Micha elsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med May 5;364(18): Erratum in: N Engl J Med Oct 20;365(16): Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, Whelan DB,Weiler PJ, Laupacis A. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA Feb 23;305(8): The odds ratio is very suspect because risk depends on multiple factors including: Age Sex Race Duration of treatment Time since stopping treatment Medical conditions/meds (steroids, HT) The highest risk is. A prior AFF on the contralateral femur 14

15 Years bisphosphonate Rx after 1st AFF Bilateral AFF - After index AFF No Bilateral AFF - After index AFF Incidence Bilateral AFF % % % % Atypical Femur Fractures The risk of a contralateral atypical femur fracture is decreased by 65.6% (p = 0.023) if bisphosphonates were stopped within the first year after the index atypical femur fracture. Key Points to Remember 15

16 #1 Is This A Stress (Atypical) Femur Fx Xray finding are key to understand Usually on bisphosphonates 5 years or more Younger patients than typical femur fxs Almost all women Prodromal pain in most patients (~70%) Often bilateral changes on xrays (~ 50%) More common in Asians and Whites Often taking steroids Findings and Stages Location - Subtrochanteric or Diaphysis Thick cortex laterally > than medially Flaring of lateral cortex with/without lucency Fx Transverse (lateral) short oblique Bilateral changes >50% Stage 1 Thick lateral cortex and pain Stage 2 Dreaded Black Line Stage 3 Complete fracture #2 What Are Complications of AFF Thick cortex and bowing on an AP view make placing a rod a challenge without over-reaming Delayed healing is common Stress Fx line may not heal while a bridging callus is common (rods are better than plates) 25% of patients fracture the other femur at same site (subtroch or shaft) Short rod may be bad idea 16

17 #3 Surgical Plan Plan for a long rod Over-ream if bowed or thick cortex Don t comminute the fracture Have blood available #4 Post-Op Plan Expect possible delayed healing, higher non-union Expect to see changes on the other femur in 50-70% of cases Expect the other femur to fracture ~18% if you stop bisphosphonates right away, higher if you continue bisphosphonates. #5 Post-Op Plan - Medication Stop the bisphosphonate Healing may be delayed If you see delayed healing consider an anabolic bone agent like PTH 17

18 Know the risk Have a plan Do the work 10-Year Risk of Fracture without Treatment 10-Year Risk of Fracture with Treatment Proportion 4 in 10 2 in 10 Probability 40% 20% Part-to-whole Icon Array Graph 18

19 Lewiecki EM. Curr Osteoporos Rep Comparative Risks x Any Fragility Fracture (1) Hip Fracture (1) Anaphylaxis from PCN Shot 32 Death by MVA 11 Death by Murder ONJ- Osteoporosis Patient Death by Lighting Strike in NM (1) Women age (from Swedish National Bureau of Statistics and database of Olmsted County, MN, USA.) Risk per 100,000 People per Year Kanis JA et al. Osteoporos Int. 2001;12: Pharmcoepidemiol Drug Saf. 2003;12: National Center for Health Statistics. JADA. 2006;137: Comparative Risks Any Fragility Fracture (1) Hip Fracture (1) Anaphylaxis from PCN Shot 32 Death by MVA 10 Death by Murder ONJ- Osteoporosis Patient Lighting Strike in NM (1) Women age (from Swedish National Bureau of Statistics and database of Olmsted County, MN, USA.) Risk per 100,000 People per Year Kanis JA et al. Osteoporos Int. 2001;12: Pharmcoepidemiol Drug Saf. 2003;12: National Center for Health Statistics. JADA. 2006;137: MMWR 47(19); Accessed 03/11/ Accessed 03/11/2017. Image copyright@2017 Lewiecki EM. 19

20 10-Year Probabilities x 80 year-old woman with FN T-score = -3.3 Includes 0.01% Atypical Femur Fracture Risk Includes 0.5% Atypical Femur Fracture Risk Untreated probability of major osteoporotic fracture calculated by FRAX. ONJ estimate is ~1/100,000 patienttreatment-years from ASBMR Task Force by Khosla S et al. J Bone Miner Res 2007;22: AFF estimate untreated is ~0.01/10,000 and treated is ~5/10,000 patient-years from Schilcher J et al. N Engl J Med. 2011;364: Risk estimates assume long-term bisphosphonate therapy resulting in 50% reduction in fracture risk. MVA and murder data from the CDC at Image copyright 2011 Lewiecki EM. Slide version. 10-Year Probabilities 80 year-old woman with FN T-score = -3.3 Includes 0.01% Atypical Femur Fracture Risk Includes 0.5% Atypical Femur Fracture Risk Untreated probability of major osteoporotic fracture calculated by FRAX. ONJ estimate is ~1/100,000 patienttreatment-years from ASBMR Task Force by Khosla S et al. J Bone Miner Res 2007;22: AFF estimate untreated is ~0.01/10,000 and treated is ~5/10,000 patient-years from Schilcher J et al. N Engl J Med. 2011;364: Risk estimates assume long-term bisphosphonate therapy resulting in 50% reduction in fracture risk. MVA and murder data from the CDC at Image copyright 2017 Lewiecki EM. Slide version. Benefits and Risks Motor Vehicle Accidents Osteoporosis Wearing seat belts reduces the risk of serious crash-related injuries and deaths by about 50% Treatment with bisphosphonates reduces the risk of fractures by about 50% There are about 2.3 million adults treated in ERs each year for injuries from MVAs and about 2 million osteoporotic fractures each year. The risk of seat belt injuries and serious side effects from osteoporosis treatment is very small in proportion to the benefits. Data from multiple sources. 20

21 Cohen JT et al. Health Affairs. 2007;26: Similar Risk with Aspirin and Cars Treatment/Activity Aspirin for prevention of CV disease and cancer in 50 year-old men Fatality Risk per 100,000 Person-years 10.4 Auto travel 11 Bicycling 2.1 Rock climbing 36 Cause of Death Stroke and noncerebral complications But what about the benefits? Cohen JT et al. Health Affairs. 2007;26: Comparative Risks of Transfusion Lee DH et al. Transfusion. 2003;43:

22 Communicating Risk Lifetime risk of breast cancer in a 50 year-old woman is 9% Schapira MM et al. Med Decis Making. 2001;21: Sequential Array Graphs of Fx Risk 75 year-old Caucasian woman with FN T-score = -3.0 Untreated Treated Sequential Array Graphs of Fx Risk 75 year-old Caucasian woman with FN T-score = % 10% 0.007%. Untreated Treated Treated ONJ 22

23 67 Why don t we see AFF in patients receiving yearly dosing of bisphosphonates like Zolidronic Acid (Reclast/Zometa) Why does the risk differ by duration of BP, race, prior BP The largest risk factor is a prior AFF Is every at the same inherent risk of getting an AFF Can we build a risk benefit calculator for bisphosphonates Why do we still use bisphosphonates besides generics being dirt cheap Other meds far less safe Approximately 107,000 hospitalizations and 3,200 to 16,500 deaths annually were found to be attributable to the use of NSAIDs in USA From 1999 to 2015, more than 183,000 people have died in the U.S. from overdoses related to prescription opioids (33,091 deaths in 2015) 1000 ER visits per day 23

24 24

25 DBL - Dreaded Black Line 25