Clinical Data and Efficacy in the Treatment of Vertebral Compression Fractures Author Affiliation 1
Perception vs. Reality Perception Patients get better by themselves with bed rest Vertebroplasty doesn t work Vertebral Augmentation (VA) doesn t work VA is more costly than doing nothing Fractures are rapidly decreasing in number 2 Reality Vertebroplasty does work Augmentation does work Mortality & costs increase when VCF not treated Fractures remain a large societal problem Cement viscosity and radio-opacity vary 2
Osteoporosis Epidemiology 10 million Number of Americans with the diagnosis of osteoporosis. [T-score <2.5] 80% are women.1 700,000 Spine fractures that occur annually. These exceed occurrence of hip and wrist fractures combined.2 $19 billion National and direct expenditures (hospitals and nursing homes) for osteoporotic and associated fractures in 2005 were estimated at $52 million each day. Since then, the cost has risen.3 150,000 People hospitalized due to pain and need medical management associated with VCFs.3 8 Average number of days patient who suffered a VCF requires hospitalization.4 1. 2. 3. 4. Cosman F, Clinician s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014; 25(10): 2359 2381 Riggs BL, 3. Melton LJ 3rd.. Bone. 1995;17 Suppl 5:S505-511 Burge R et al. J Bone Miner Res 2007 Vol 22. No.3 p 465 475 Cooper C et al. J Bone Min Res. 1992;7:221 227 3
Under Diagnosed and Untreated Two thirds of all vertebral fractures go undiagnosed History not specific it hurts everywhere Co-morbidities take priority (cardiac, pulmonary) Low index of suspicion 42% of symptomatic fractures not collapsed on radiographs Moderate or severe fractures reported only 50% of the time Only 20% of osteoporosis related VCF patients receive bone testing or treatment within a year. Singer AJ. Understanding the Downward Spiral and Mortality Risk for Patients with Vertebral Compression Fractures. National Osteoporosis Foundation. Retrieved from https://vimeo.com/190767688. 4
VCF Risk Factors Bone mineral density Age Sex Fracture deformity Prior fracture Bone affecting drugs Steroids 2.6 x risk Chemotherapy and BMT Seizure medications Cosman F, Clinician s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014; 25(10): 2359 2381 Riggs BL, Melton LJ III. Bone. 1995;17 Suppl 5:S505-511 5
VCF Risk: Age & Sex Higher in women than men at any age due to low BMD Risk increases with age, independent of BMD EPOS Group. J Bone Miner Res. 2002 Apr;17(4):716-24. 6
VCFs Increase Risk of New Fractures Prevalence of vertebral fractures are highly significant predictors of additional fracture incidence 1 5-fold increased risk of a new vertebral fracture 2-fold increased risk of hip fracture 2,3 12-fold after 2 or more VCFs3 1. Ross et al. Annals of Internal Medicine 1991:114(11): 919-923 2. Black DM et al. J Bone Miner Res 1999:14(5):821-8 3. Melton LJ 3rd et al. Osteoporosis Int 1999:10(3):214-221 7
Increased Mortality Relative Risk of Death in 3.8 yrs 11 6.68X 9 8.64X 7 5 2 1X 0 Age-Matched Control Hip Fracture Spine Fracture Cauley JA, Osteoporosis Int. 2000;11(7) p556-61 8
MEDPAR data support clinical benefit of MI Procedures in VCF Treatment Impact of Nonoperative Treatment, Vertebroplasty and Kyphoplasty on Survival and Morbidity after VCF in Medicare Population1 2006 MEDPAR data on 68,752 patients demonstrate improvement in post-discharge survival and morbidity Patients managed non-operatively more likely to die during index hospitalization Increased 3 year survival rate, shorter hospital stay, least likely to have pneumonia and decubitus ulcers Consistent with Edidin review of 858,978 Medicare population - increase mortality risk in non-operated patients 2 1. Chen AT et al. Bone Joint Surg Am 2013 v95 p1729-36 2. Edidin AA et al. J Bone Miner Res 2011 v26 p1617-26 9
Medical Management and bed rest considerations Medical management often involves bed rest1 as few as 2 days of bed rest lead to bone mass loss2 by 1 week, the rate of bone loss is 50 times the normal age-related rate3 after 10 days, 15% of aerobic capacity and lower extremity strength is lost, equivalent to 10 years of age-related loss.4 Adding narcotic anesthesia and associated adverse effects of sedation, nausea, and constipation further increases physical deconditioning and fall risk, and prolongs recovery.1 1. 2. 3. 4. 1 0 Chandra RV et al. AJNR Am J Neuroradiol 2017 Nov 23 Baecker N et al. J Appl Physiol 2003;95:977 82 Marie PJ et al. J Clin Endocrinol Metab 2011;96:600 09 Kortebein P et al. J Gerontol A Biol Sci Med Sci2008;63:1076 81 10
Under-treatment based on misinterpretation of VP/VA evidence in 2009 Clinical Evidence Background Minimally invasive vertebral augmentation topic of much debate 4 Prospective Randomized Trials published in NEJM and Lancet re: efficacy of MI procedures NEJM: no statistical significant clinical difference 1,2 Vertebroplasty vs. Sham procedure (facet block) Note: sham is not SOC conservative management; rarely used in clinical practice Lancet: statistically significant clinical difference 3,4 Vertebroplasty / Vertebral Augmentation (kyphoplasty) vs. SOC medical management MI procedures resulted in near and long term (1 year) improvement Cost effectiveness shown 1. 2. 3. 4. Kallmes D et al. N Engl J Med 2009; 361:569-579 Buchbinder R et al. N Engl J Med 2009; 361:557-568 Wardlaw D et al. Lancet 2009; 373:1016-1024 Klazen et al. Lancet 2010; 376:1085-1092 11
Comparison of NEJM and Lancet Studies CON Study NEJM studies (Kallmes/Buchbinder) Lancet studies (Wardlaw/Klazen) Multicenter, randomized controlled Control: sham injection at periosteum Patients blinded Multicenter, randomized controlled Control: Conservative care Inclusion Time past fracture < 1 year Back pain 3 (0-10 scale) Follow up Buchbinder 6 months Kallmes 3 month Endpoints Pain relief at 1 week, 1,3, 6 months RDQ disability questionnaire (Kallmes) Outcome PRO Time past fracture < 6weeks Edema evidence on MRI Back pain >5 (0-10 scale) FREE and VERTOSS 12 months Change in SF 36 PCS (physical component summary) baseline to 1 month in (FREE) Pain relief at 1 & 12 mos. (VERTOS) Vertebroplasty numerically better, but not statistically for both RDQ & pain relief Statistically & clinically significant 43% sham treated patients crossed over to improvement in SF 36 PCS and pain score in vertebroplasty treatment after 3 mos. favor of MI procedures Only 12% of vertebroplasty crossed over to sham 12
Analysis of Reporting Bias in Vertebral Augmentation Kallmes et al and Buchbinder et al found no beneficial effect of cement augmentation when VP was compared with paraspinal injection of local anesthetic (sham) Both studies have been downgraded after further review and scrutiny Since 2009, there have been 6 prospective randomized controlled trials (PRCTs) on VA for treatment of OVCF 5 have shown superior results with VA as compared with NSM Beall DP et al. Pain Physician. 2017 Nov;20(7) :E1081-E1090 13
Prospective and Multicenter Evaluation of Outcomes for Quality of Life and Activities of Daily Living for BKP in Treatment of VCFs: EVOLVE Study 350 patients with painful VCFs enrolled and treated with BKP across 24 sites Etiology: 97% osteoporosis; 2% cancer Acute or subacute ( 4 mos.); pain 7 on PE and correlated imaging; ODI 30 Coprimary endpoints at 3mos post kyphoplasty significantly improved (p <.001): Numerical Rating Scale (NRS) back pain: 8.7 to 2.7 Oswestry Disability Index (ODI): 63.4 to 27.1 Short Form-36 Physical Component (SF-36v2 PCS): 24.2 to 36.6 EuroQol-5-Domain (EQ-5D): 0.383 to 0.746 Improvement in all outcomes at 7d, 1, 3, 6, and 12 mos. statistically significant Demonstrates kyphoplasty is safe, effective and provides durable Beall DP et al. Neurosurgery. 2018 Mar 14. doi: 10.1093/neuros/nyy017 14
Percutaneous Vertebral Augmentation: Augmentation: A Consensus Statement Percutaneous Vertebral A Consensus Standards of Statement Practice Vertebral Augmentation Joint Position Statement Percutaneous Vertebral Augmentation (PVA) remains a proven medically appropriate therapy for treatment of painful VCFs Multiple case series, retrospective and prospective non-randomized studies and, more recently, randomized controlled trials have shown statistically significant improvement in pain and function, particularly ambulation PVA (vertebroplasty or kyphoplasty) is a safe, efficacious, and durable procedure (SIR) Society of Interventional Radiology (AANS) American Association of Neurological Surgeons (CNS) Congress of Neurosurgeons (ACR) American College of Radiology (ASNR) American Society of Neuroradiology (ASSR) American Society of Spine Radiology (CIRA) Canadian Interventional Radiology Association (SNIS) Society of Neuro Interventional Surgery JD Barr et al. J Vasc Interv Radiol. 2014 Feb;25(2):171-81. 15
Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR); a multicenter, randomized, double-blinded, placebo-controlled trial 120 pts enrolled and treated: 61 Vertebroplasty and 59 Placebo VCF < 6 wks; pain > 7/10 with concomitant MRI (or SPECT-CT) 57% patients were hospital inpatients indicating severe disability Controlled for age, height loss, steroids, trauma True Placebo: SQ lidocaine not periosteal infiltration Follow up @ 3d, 14d, and 1, 3, and 6 months Primary Outcome: pain < 4/10 at 14 days Vertebroplasty 44% vs. Placebo 21% (p=0.011) Clark W, Lancet 2016 Oct 1_388_10052 p1408-1416 16
VAPOUR Trial Improved scores favorable to VP across all study measurements Median duration of hospital stay reduced by 5.5 days in VP group Vertebral body height loss @ 6-months: 27% loss in VP vs. 63% loss in placebo group Clark W, Lancet 2016 Oct 1_388_10052 p1408-1416 17
Referral Messaging Regarding Efficacy of Procedures for VCFs How to identify patients likely to benefit from procedure? 1 Patient history Acuity of fracture Pain on a pain scale of 1-10 Physical examination MRI (best) or bone scan + CT (patient unable to undergo MRI): MRI can show edema (evidence of recent fracture) and document location Rationale for patient selection/objective of treatment 2 Fracture stabilization results in Immediate pain relief» reduced bed rest, narcotic use & associated co-morbidities» reduced muscle flaccidity, loss of bone mass, instability and GI distress 1. JD Barr et al. J Vasc Interv Radiol. 2014 Feb;25(2):171-81 2. Chandra RV et al. Am J Neuroradiol. 2017 Nov 23. 18
Intervention Criteria / Patient Selection Pain unrelieved by narcotics Decreased mobility Radiographic evidence of fracture Pain localized to fracture level Non-focal neurologic examination 19
Natural History? T12 Vertebral Compression Fracture January 2003 February 2003 Courtesy of Michael Hisey, M.D. Texas Back Institute 16000229-01 Nevitt MC et al. Bone. 1999;25:613 619. Cooper C et al. J Bone Min Res. 1992;7:221 227. March 2003 20
Intervention Criteria Changing Patient Selection Early intervention Early ambulation and rehab Decrease hospitalization period Prevent further injury (acute on chronic) 21
Diagnosing VCF Patient who is >50 years old with sudden onset of back pain Physical examination Tenderness over area of possible fracture Muscle spasm Pain with movement and standing Lateral spine radiograph can screen for VCF MRI confirms diagnosis Beware of infection and unstable fractures 22
VCF Diagnosis and Acuity MRI Determines fracture acuity Differentiates: discs, metastatic disease T2/STIR (Bright) Edema Clefts T1 (dark) Edema Fracture lines 23
VCF Diagnosis and Acuity Bone Scan with SPECT If MRI is contraindicated; ICD Increased tracer in areas of high bone activity Increased uptake in fractured bone for months, depending on degree of remodeling identifies new and recently healed fractures 3 phase scan can assist in determining acuity Remember: delay in becoming positive in elderly. Age equals hours L1 L2 L3 24
VCF Diagnosis and Acuity CT Excellent for delineating osseous anatomy Sagittal images key Fracture plane generally easy to visualize Difficult to determine age of fracture Compare with Prior Imaging 25
Treatment Options Conservative Management Pain medications Back brace to provide support and stability Bed rest Physical Therapy Minimally Invasive Surgery Vertebroplasty Vertebral augmentation Balloon Kyphoplasty Targeted Vertebral Augmentation Open Surgery Limited to neurologic deficit, 3 column instability Significant rehabilitation time and effort required 26
Minimally Invasive Surgery Vertebroplasty Uses local, moderate sedation, or general anesthesia 11g-13g needle guided into the fractured vertebra Bone cement injected into the fractured vertebra Needle removed. Cement hardens in ~10 mins Limitations: Thinner cement, may leak before optimal fill achieved Hands near beam Higher rate of asymptomatic cement leakage 27
Minimally Invasive Surgery Balloon Kyphoplasty Uses moderate sedation or general anesthesia Balloon placed into the vertebra and inflated Balloons create a cavity within the vertebral body Cement injected after balloons removed to stabilize fracture Limitations: Large cement bolus with variable degrees of filling fracture planes Routinely performed Bi-pedicular Radiation exposure 28
Evolution of Treatment Options Advanced Augmentation Options Balloon Kyphoplasty (BKP) Vertebroplasty (VP) Invasive Spine Surgery or Medical Management 29
Innovation in VCF Treatment: Targeted Vertebral Augmentation PowerCURVE Navigating Osteotome enables targeted vertebral access across midline via a unipedicular approach Targeted cavity creation spares cancellous bone as it creates preferential pathways for distribution of high viscosity StabiliT cement Targeted pathways maximize surface area for cement interdigitation resulting in predictable fill and stability 30
2015 DFINE Inc. All rights reserved. PML5245-AA Targeted Cavity Creation Introduction of osteotome into vertebral body and initial articulation Navigating Osteotome: creates preferential paths for delivery of bone cement allows for bone sparing targeted cavity creation unipedicular approach Articulation and navigation of the osteotome across the vertebral midline Preferential bone cement delivery through targeted cavities Dalton BE, Clin Interv Aging 2012 v7 p525-31 31
Why Targeted Vertebral Augmentation (TVA) Creates targeted cavities to improve cement flow and distribution (Navigational Osteotome/Steerable Balloon) High viscosity cement Interdigitation Consistent high viscosity cement over extended period of time Less leakage Option to control cement delivery from a distance can help reduce radiation dose to operator 1 Long working time cement Easy to perform 2 level case in 1 batch 1. Lüdeke et al. 66th German Society of Neurosurgery (DGNC) 8June2015. MO16.06 32
Navigational Technology to permit targeted therapy Navigational Targeted Cavity Creation PowerCurve Osteotome Steerable Balloon 33
Continuing Conservative Care vs Crossover to TVA: Comparative Effectiveness Significantly reduced pain and disability 65 patients were treated with conservative care 33 patients chose to cross over to TVA after conservative care Conclusions Vast majority of patients with VAS 5, conservative care did not provide meaningful clinical improvement In contrast, 31/33 patients who underwent TVA had significant improvement in pain & function Improvement in pain and disability (p< 0.001) Pain (VAS pts) Function (ODI %) 6 Weeks post conservative care 0 6 3-4 days post TVA 5 30 6 weeks post TVA 5 38 Bornemann R. et al. Eur Spine J 2012 v21 p930-6 34
Comparison of Clinical & Radiological Data in Treatment of Osteoporotic VCFs: TVA or BKP Reduced pain, procedure time and risk of cement extravasation VAS Improvement Post Op VAS Improvement 6 months (p> 0.02 ) (p> 0.001) Targeted Vertebral Augmentation (TVA) 70% Balloon Kyphoplasty (BKP) 65% 86% n=103 70% n=91 Procedure (Minutes) Cement Extravasation (p>0.001) (p> 0.0001) 28.2 6.10% 49.6 27.20%* Pflugmacher R, et al. Z Orthop Unfall 2012;150:56-61 35
Treatment of VCFs due to Multiple Myeloma Number of patients Number of patients 66 TVA procedures performed 10-point visual analog scale (VAS) to assess pre/post-op back pain Pain medication changes recorded Significant decrease in pain, and increase in activity Significant decrease in narcotic use observed at 6 months Erdem, E. et al. Spine 2013.38.1275 1281 36
TVA Case L2 72 year old woman Referred for L2 fracture MRI: Old L2 fx L3 Edema and fx Courtesy of D. Enterline, M.D. Duke University 37
Navigational Osteotome bone sparing targeted cavity creation Additional preferential cavity creation Initial Cement Delivery Cement filling compromised areas of bone Controlled Delivery of High Viscosity Cement Optimal cement fill Courtesy of D. Enterline, M.D. Duke University 38
StabiliT Vertebral Augmentation Systems Indications for Use StabiliT Vertebral Augmentation Systems are intended for percutaneous delivery of StabiliT Bone Cement. The StabiliT bone cement is indicated for the treatment of pathological fractures of the vertebrae using a vertebroplasty or kyphoplasty procedure. Painful vertebral compression fractures may result from osteoporosis, benign lesions (hemangioma),and malignant lesions (metastatic cancers, myeloma) Risks and Contraindications As with most surgical procedures, there are risks associated with the StabiliT procedure, including serious complications. For complete information regarding risks, contraindications, warnings, precautions, and adverse events please review the System s Instructions for Use 39
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