1、Vertebral Compression Fractures,What should we be doing? (or not doing .)Debra L. Bynum, MD Division of Geriatric Medicine University of North Carolina,“ I firmly believe that if the whole materia medica as now used, could be sunk to the bottom of the sea, it would be all the better for mankind, - a
2、nd all the worse for the fishes”Oliver Wendell Holmes, address to the Massachusetts Medical Society, 1860,Objectives,Understand the theory and basic procedure involved in kyphoplasty and vertebroplastyBe able to weigh the risks and benefits associated with these proceduresIdentify key management str
3、ategies in patients with compression fractures,Case,An 89 year old woman with HTN, mild cognitive impairment, and osteoporosis is admitted with 2 weeks of back pain and is found to have a new thoracic compression fracture. Her daughter is a cardiologist at Duke and is interested in pursuing possible
4、 vertebroplasty.,From one website,“A new therapy, Percutaneous Vertebroplasty, is very effective in the management of pain caused by vertebral compression fractures. Percutaneous vertebroplasty can result in relief of pain in 80-90% of patients. The relief is usually achieved within 3 days of the pr
5、ocedure. For more information about this advanced procedure, speak to your pain management physician”,The case,You ask a colleague about vertebroplasty, and you are toldA nonblind but randomized study in March showed benefit, but two recent blinded, randomized controlled studies showed no benefitHe
6、recommends “shared decision making” talk to the daughter and let her decide,Background: Vertebral Compression Fractures,Over 700,000 /year in U.S. 80% prevalence in women over age 80 Complications: Acute pain and chronic pain Pulmonary dysfunction Loss of mobility Chronic spinal deformity Depression
7、 ?increased mortality (marker of frailty) Costly: $ 14 billion/year,Background:Vertebroplasty,Vertebroplasty (VP) introduced in France in 1984 by interventional neuroradiologistVP used in US in 19931997: First case series of VP in U.S.,Kyphoplasty,Attempt to restore vertebral body height and reduce
8、kyphosis by using inflatable balloon tampOrthopedic surgery 1998Height restoration (may be only 3-4 mm)More expensive, often with general anesthesiaLess risk of cement leak,Background Data (prior to recent studies of controversy),Multiple small studies of VP demonstrating greater pain reduction, les
9、s analgesic use, and greater mobility compared to medical management (initially and at few months)3 meta-analyses show reduction in painMinimal complications,Background (cont),KP with similar history: multiple small studies demonstrating benefit with quicker reduction in pain and mobilization compar
10、ed to medical treatmentKP and VP: no studies clearly demonstrated any benefit 1-2 years later when compared to medical treatmentProcedures have increased exponentially Cement material previously FDA approved No FDA oversight for new procedures,KP vs VP: Which is better?,KP: goal to restore height/re
11、duce kyphosis, but may only increase by 2-4 mm (no sig difference with VP)KP with less cement leak ( 1% vs 3 % or more with VP), although most leaks not symptomaticPain and other outcomes similarMost likely similar, although patients referred for KP often have more severe fractures,Complications,Cem
12、ent LeakCement Pulmonary embolism (?higher than thought)Cord compressionHematoma, infection,Complications,?adjacent vertebral fractures (probable)Most studies show increased riskProblem: patients with compression fractures have high probability of future fractures (25%/year)Confounding: Those with w
13、orse disease more likely to have VP/KP and more likely to have future fractures,Background Way Back,Long history of brave exploration of new procedures and surgeriesTrephination of the skull, 10,000 BCFirst appendectomy, 1736Coronary stenting, spinal fusion, and now vertebroplasty,Weinstein J. N Eng
14、l J Med 2009;361:619-621,Ratios of Medicare Vertebroplasty Rates to the U.S. Average, According to Hospital Referral Region (2001-2006),Fracture Reduction Evaluation (FREE) trial,Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture: a randomis
15、ed controlled trialLancet March 2009,FREE trial,Patients with 1-3 acute vertebral fractures149 patients randomized to KP, 151 controlsPrimary outcome: change from baseline to 1 month in SF-36 physical component score (PCS)Also measured: QOL, safety up to 12 months,FREE: results,Mean PCS score improv
16、ed 7.2 points (0-100 scale) in KP group and only 2 points in control group at 1 monthMore patients in control group needed walking aids, back braces, PT, analgesicsKP: greater improvement in QOLKP : 2.9 less days of restricted activity at 1 moNo significant differences at 12 months,Results,KP Contro
17、lbase 1month 12month base 1month 12mo Walking aid/brace 71% 33% 26% 72% 61% 41% Bedrest (1d/14d) 58% 23% 4% 64% 42% 8% Combo analgesic 58% 41% 24% 56% 57% 29% Opioid 16% 5% 4% 12% 8% 5%,FREE: problems,Excluded patients with dementiaNot blinded (patients and radiologists)Funded by Medtronic Spine12 m
18、onths: 38 (33%) in KP group and 24 (25%) had new/worsening VCF (p=.22),Take Home (at the time),Despite the problems, a well designed trialAlthough no significant difference at 12 monthsReduction in short term bedrest and need for opioid analgesics that may be significant in this populationRecommende
19、d as possible benefit to select patients,New information,NEJM August, 2009,Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures,131 patients with 1-3 painful osteoporotic vertebral compression fractures Vertebroplasty vs simulated procedurePrimary outcome: Disability Questionnaire (h
20、igher score=greater disability) and patients rating of pain,RCT,1 month: no significant difference in RDQ score or pain rating (trend toward improved pain in 64 % VP group vs 48 % control, p =.06)Both groups had immediate improvement in disability and pain scores,Randomized Trial of Vertebroplasty f
21、or Painful Osteoporotic Vertebral Fractures,Double blind, placebo controlled, RCTPatients with 1-2 painful osteoporotic vertebral fractures less than 12 months and “unhealed” on MRIPrimary outcome: Pain at 3 months78 patients, 71 completed 6 month follow up,Results,No difference between groupsBoth h
22、ad significant reduction in pain at 1 week, 1 month, 3 months, and 6 months3 months (2.6 points in VP group, 1.9 in control group)Similar improvements in both groups with physical functioning, QOL, and perceived improvement,Why the difference?,The RCT as Gold Standard,1753: naval surgeon James Lind
23、publishes account of comparative treatment of 12 scurvy patients:“their cases as similar as I could have them the most sudden and visible good effects were perceived from the use of the oranges and lemons”,The RCT,1930: Sollman suggests approach to problem of investigator bias: use of blinded observ
24、er and a placebo control1932-1937: Harry Gold at Cornell refines the double blind method and use of placebo1935: Ronald Fishers “The Design of Experiments” argues for use of strictly randomized allocation,The RCT,Randomization made test groups more comparable and “ethical”1947: limited supply of str
25、eptomycin for British patients, Bradford Hill in the BMJ pushed for studies with a randomized design:“precluded the biases introduced by our personal idiosyncracies, consciously or unconsciusly applied, or lack of judgment”,RCT,1960s: increase value on statistical evidence in interpreting evidence19
26、90s: Evidence Based Medicine,Wont get fooled again,Hip protectors and decreased hip fractures Estrogen use in postmenopausal women decreases the risk of CAD (women on estrogens live 1.5 years longer than those not) Early coronary intervention must be good for patients with diabetes and evidence for
27、significant but asymptomatic coronary disease on angiography Maybe trephination.,Problems with prior studies looking at VP and KP,Not blinded Bias on part of investigators (evidence that it“works”) Bias of participants (advertised “evidence” that this works)Underestimated placebo effect Emphasis on
28、“bioplausibility” (like HRT studies)Favorable natural history of this diseaseConfounders that no math can control for (HERS study),Are the results really different?,Although not “significant”, some suggestion that pain is decreased at 1 month (similar to FREE study)Care with “not significant” as stu
29、dies may not have the power to see a differenceAlthough effect likely to be smallAre we assuming too much that KP and VP are similar in effect?,Concerns about the Validity of most recently reported studies,Outpatients (inpatients may have more severe pain)Patients received 4 weeks of medical treatme
30、nt patients on average had 9-16 weeks of symptoms in the 2 recent VP studies (compared to 6 weeks for the Lancet KP study)Counter: no difference in subgroup analysis between patients with less than or more than 6 weeks of symptoms,Take Home,VP likely not much better than conservative treatment, pain
31、 control, PTTime will healUnclear what to do with KP, although likely similarVP and KP not without risk,Other Treatments,Calcitonin for pain: Fact or Lore?,Systematic review, only 5 decent randomized, controlled studiesReduced pain, immobility, analgesic useMay help, take with a grain of salt,Calciu
32、m and Vitamin D,Evidence that Ca and Vitamin D reduce fractures1200 mg/day Calcium,Vitamin D,Mounting evidence that deficiency is pandemicRisk factors: darker skin, obesity, older age, institutionalizationReceptors in every organRelationship with sarcopenia and wastingRelationship to falls,Vitamin D
33、 refresher,D2 Ergocalciferol Plants, dietary D3 Cholecalciferol Sun exposure (UVB) and animal (salmon, cod liver) Metabolized 25 (OH) D in liver 1,25 (OH) D in kidneys,Vitamin D: deficiency,25 (OH) D levels30: not deficient Many need supplementation Cannot recommend increase sun exposure Difficult t
34、o get enough in diet,Vitamin D: replacement,400 IU with MVIDaily recommendations for those at risk: 800- 1000 IUReplacement: 50,000 IU /week for 4-6 weeks, recheck Many will need to continue 50,000 /month,Other Treatment options,Braces Poor adherence If cord compromise/retropulsion, may need shell L
35、ess restrictive: Jewitt May reduce pain by decreasing postural flexion,Jewitt Brace,Treating Osteoporosis,Antiresorptive agents Block osteoclastic activity Bisphosphonates Estrogen/hormone therapy Raloxifene CalcitoninAnabolic agents Stimulation of osteoblastic activity Teriparatide (recombinant PTH
36、),Treating Osteoporosis,Despite evidence that multiple agents decrease future vertebral fractures, few patients evaluated or treated after first fragility fracture.,What Next?,How do we truly evaluate the efficacy of procedures?,Health Technology Assessment (HTA) program,Washington state legislature
37、 2006Government sponsored program using formal methods to conduct critical appraisals of surgical devices and procedures, medical equipment, and diagnostic testsFDA: low standards for devices, and surgical procedures not regulated,HTA,Pediatric bariatric surgery Lumbar fusion CT colonography Arthros
38、copy for OA of knee Coronary CT angiography,Obstacles,Industry pressure (pressure put on Medicare to cover )Difficult to translate analysis of evidence (effectiveness, safety, cost-effectiveness) into coverage decision?buy in from patients and providers?Gary Franklin and Brain Budenholzer, NEJM Oct
39、2009,Summary Points: Vertebral Compression Fractures,Most will heal with timeNo clear evidence that VP or KP are better than placebo over timeKP does not improve kyphosis, but may have less risk of cement leakPatients with vertebral compression fractures have high risk of future fractures; There lik
40、ely is a real increase with VP or KP,Summary Points,Even in the most recent articles, there may be a tendency toward decreased pain initially after VPThere may be a role for patients who are hospitalized with severe pain requiring narcotics (small benefit in this group may be worth the risk),Summary Points,Consider Jewitt brace for comfortCalcitonin may help for painCheck for and treat vitamin D deficiencyTreat the osteoporosis,Summary . Final Points,No procedure is without riskNo statistical analysis is without riskTreat the Osteoporosis,
