1. Vertebral Compression Fractures… What should we be doing? (or not doing ….) Debra L. Bynum, MD Division of Geriatric Medicine University of North Carolina

2. “… 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, -- and all the worse for the fishes” Oliver Wendell Holmes, address to the Massachusetts Medical Society, 1860

3. Objectives Understand the theory and basic procedure involved in kyphoplasty and vertebroplasty Be able to weigh the risks and benefits associated with these procedures Identify key management strategies in patients with compression fractures

4. 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 vertebroplasty….

5. 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 procedure. For more information about this advanced procedure, speak to your pain management physician…”

6. The case… You ask a colleague about vertebroplasty, and you are told  A nonblind but randomized study in March showed benefit, but two recent blinded, randomized controlled studies showed no benefit  He recommends “shared decision making” – talk to the daughter and let her decide…

7. 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  ?increased mortality (marker of frailty)  Costly: $ 14 billion/year

9. Background:Vertebroplasty Vertebroplasty (VP) introduced in France in 1984 by interventional neuroradiologist VP used in US in 1993 1997: First case series of VP in U.S.

10. Kyphoplasty Attempt to restore vertebral body height and reduce kyphosis by using inflatable balloon tamp Orthopedic surgery 1998 Height restoration (may be only 3-4 mm) More expensive, often with general anesthesia Less risk of cement leak

11. Background Data (prior to recent studies of controversy…) Multiple small studies of VP demonstrating greater pain reduction, less analgesic use, and greater mobility compared to medical management (initially and at few months) 3 meta-analyses show reduction in pain Minimal complications

12. Background (cont) KP with similar history: multiple small studies demonstrating benefit with quicker reduction in pain and mobilization compared to medical treatment KP and VP: no studies clearly demonstrated any benefit 1-2 years later when compared to medical treatment Procedures have increased exponentially  Cement material previously FDA approved  No FDA oversight for new procedures…

13. KP vs VP: Which is better? KP: goal to restore height/reduce 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 symptomatic Pain and other outcomes similar Most likely similar, although patients referred for KP often have more severe fractures

14. Complications Cement Leak Cement Pulmonary embolism (?higher than thought) Cord compression Hematoma, infection

15. Complications… ?adjacent vertebral fractures (probable)  Most studies show increased risk  Problem: patients with compression fractures have high probability of future fractures (25%/year)  Confounding: Those with worse disease more likely to have VP/KP and more likely to have future fractures

16. Background – Way Back… Long history of brave exploration of new procedures and surgeries…  Trephination of the skull, 10,000 BC…  First appendectomy, 1736  Coronary stenting, spinal fusion, and now vertebroplasty…

17. Weinstein J. N Engl J Med 2009;361:619-621 Ratios of Medicare Vertebroplasty Rates to the U.S. Average, According to Hospital Referral Region (2001-2006)

18. Fracture Reduction Evaluation (FREE) trial Efficacy and safety of balloon kyphoplasty compared with non- surgical care for vertebral compression fracture: a randomised controlled trial Lancet March 2009

19. FREE trial Patients with 1-3 acute vertebral fractures 149 patients randomized to KP, 151 controls Primary outcome: change from baseline to 1 month in SF-36 physical component score (PCS) Also measured: QOL, safety up to 12 months

20. FREE: results Mean PCS score improved 7.2 points (0-100 scale) in KP group and only 2 points in control group at 1 month More patients in control group needed walking aids, back braces, PT, analgesics KP: greater improvement in QOL KP : 2.9 less days of restricted activity at 1 mo No significant differences at 12 months…

21. Results KPControl base1month12monthbase1month12mo 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%

22. FREE: problems… Excluded patients with dementia Not blinded (patients and radiologists) Funded by Medtronic Spine 12 months: 38 (33%) in KP group and 24 (25%) had new/worsening VCF (p=.22)

23. Take Home (at the time) Despite the problems, a well designed trial Although no significant difference at 12 months… Reduction in short term bedrest and need for opioid analgesics that may be significant in this population Recommended as possible benefit to select patients…

24. New information… NEJM August, 2009

25. Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures 131 patients with 1-3 painful osteoporotic vertebral compression fractures Vertebroplasty vs simulated procedure Primary outcome: Disability Questionnaire (higher score=greater disability) and patient’s rating of pain

26. 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

27. Randomized Trial of Vertebroplasty for Painful Osteoporotic Vertebral Fractures Double blind, placebo controlled, RCT Patients with 1-2 painful osteoporotic vertebral fractures less than 12 months and “unhealed” on MRI Primary outcome: Pain at 3 months 78 patients, 71 completed 6 month follow up

28. Results… No difference between groups Both had significant reduction in pain at 1 week, 1 month, 3 months, and 6 months 3 months (2.6 points in VP group, 1.9 in control group) Similar improvements in both groups with physical functioning, QOL, and perceived improvement

29. Why the difference?

30. The RCT as Gold Standard 1753: naval surgeon James Lind 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”

31. The RCT… 1930: Sollman suggests approach to problem of investigator bias: use of blinded observer and a placebo control 1932-1937: Harry Gold at Cornell refines the double blind method and use of placebo 1935: Ronald Fisher’s “The Design of Experiments” argues for use of strictly randomized allocation

32. The RCT Randomization made test groups more comparable and “ethical” 1947: limited supply of streptomycin 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 ”

33. RCT… 1960s: increase value on statistical evidence in interpreting evidence 1990s: Evidence Based Medicine…

34. Won’t 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 significant but asymptomatic coronary disease on angiography Maybe trephination….

35. 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 “bioplausibility” (like HRT studies) Favorable natural history of this disease Confounders that no math can control for (HERS study)

36. 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 studies may not have the power to see a difference  Although effect likely to be small…  Are we assuming too much that KP and VP are similar in effect?

37. Concerns about the Validity of most recently reported studies… Outpatients (inpatients may have more severe pain) Patients received 4 weeks of medical treatment – 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

38. Take Home VP likely not much better than conservative treatment, pain control, PT Time will heal Unclear what to do with KP, although likely similar VP and KP not without risk

39. Other Treatments…

40. Calcitonin for pain: Fact or Lore? Systematic review, only 5 decent randomized, controlled studies Reduced pain, immobility, analgesic use May help, take with a grain of salt…

41. Calcium and Vitamin D Evidence that Ca and Vitamin D reduce fractures 1200 mg/day Calcium

42. Vitamin D Mounting evidence that deficiency is pandemic Risk factors: darker skin, obesity, older age, institutionalization Receptors in every organ Relationship with sarcopenia and wasting Relationship to falls

43. Vitamin D… 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

44. Vitamin D: deficiency 25 (OH) D levels < 20: deficient > 30: not deficient Many need supplementation  Cannot recommend increase sun exposure  Difficult to get enough in diet

45. Vitamin D: replacement 400 IU with MVI Daily recommendations for those at risk: 800- 1000 IU Replacement:  50,000 IU /week for 4-6 weeks, recheck  Many will need to continue 50,000 /month

46. Other Treatment options… Braces  Poor adherence  If cord compromise/retropulsion, may need shell  Less restrictive: Jewitt  May reduce pain by decreasing postural flexion

47. Jewitt Brace

48. Treating Osteoporosis Antiresorptive agents  Block osteoclastic activity  Bisphosphonates  Estrogen/hormone therapy  Raloxifene  Calcitonin Anabolic agents  Stimulation of osteoblastic activity  Teriparatide (recombinant PTH)

49. Treating Osteoporosis Despite evidence that multiple agents decrease future vertebral fractures, few patients evaluated or treated after first fragility fracture….

50. What Next? How do we truly evaluate the efficacy of procedures?

51. Health Technology Assessment (HTA) program Washington state legislature 2006 Government sponsored program using formal methods to conduct critical appraisals of surgical devices and procedures, medical equipment, and diagnostic tests FDA: low standards for devices, and surgical procedures not regulated

52. HTA… Pediatric bariatric surgery Lumbar fusion CT colonography Arthroscopy for OA of knee Coronary CT angiography

53. 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 2009

54. Summary Points: Vertebral Compression Fractures Most will heal with time No clear evidence that VP or KP are better than placebo over time KP does not improve kyphosis, but may have less risk of cement leak Patients with vertebral compression fractures have high risk of future fractures; There likely is a real increase with VP or KP

55. Summary Points Even in the most recent articles, there may be a tendency toward decreased pain initially after VP There may be a role for patients who are hospitalized with severe pain requiring narcotics (small benefit in this group may be worth the risk…)

56. Summary Points… Consider Jewitt brace for comfort Calcitonin may help for pain Check for and treat vitamin D deficiency Treat the osteoporosis

57. Summary …. Final Points No procedure is without risk No statistical analysis is without risk Treat the Osteoporosis