vertebral compression fractures… what should we be doing? (or not doing ….) debra l. bynum, md...
TRANSCRIPT
Vertebral Compression Fractures…What should we be doing?(or not doing ….)
Debra L. Bynum, MDDivision of Geriatric MedicineUniversity 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, -- and 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 vertebroplasty
Be able to weigh the risks and benefits associated with these procedures
Identify key management strategies 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 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 procedure. For more information about this advanced procedure, speak to your pain management physician…”
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…
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
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.
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
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
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…
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
Complications
Cement Leak
Cement Pulmonary embolism (?higher than thought)
Cord compression
Hematoma, infection
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
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…
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)
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
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
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…
Results
KP Controlbase 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 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)
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…
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 procedure
Primary outcome: Disability Questionnaire (higher score=greater disability) and patient’s 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 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
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
Why the difference?
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”
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
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”
RCT…
1960s: increase value on statistical evidence in interpreting evidence
1990s: Evidence Based Medicine…
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….
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)
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?
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
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
Other Treatments…
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…
Calcium and Vitamin D
Evidence that Ca and Vitamin D reduce fractures
1200 mg/day Calcium
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
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
Vitamin D: deficiency
25 (OH) D levels < 20: deficient > 30: not deficient Many need supplementation
Cannot recommend increase sun exposureDifficult to get enough in diet
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, recheckMany will need to continue 50,000 /month
Other Treatment options…
BracesPoor adherence If cord compromise/retropulsion, may
need shellLess restrictive: JewittMay reduce pain by decreasing postural
flexion
Jewitt Brace
Treating Osteoporosis
Antiresorptive agents Block osteoclastic activity Bisphosphonates Estrogen/hormone therapy Raloxifene Calcitonin
Anabolic agents Stimulation of osteoblastic activity Teriparatide (recombinant PTH)
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 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
HTA…
Pediatric bariatric surgery Lumbar fusion CT colonography Arthroscopy 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 2009
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
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…)
Summary Points…
Consider Jewitt brace for comfort
Calcitonin may help for pain
Check for and treat vitamin D deficiency
Treat the osteoporosis
Summary …. Final Points
No procedure is without risk
No statistical analysis is without risk
Treat the Osteoporosis