1. NOVEL ADVANCES IN TREATMENT OF COMPRESSION FRACTURES: UPDATE IN RFA AND KYPHOPLASTY TECHNIQUES
Sponsored by
Melissa Y. Macias, MD PhD FAANS
1227 Third Street
Corpus Christi, Texas 78414
Kyphon™ Balloon Kyphoplasty incorporates technology developed by Gary K. Michelson, M.D.

2. **Disclosure:
I have no financial benefit/gain or interest in Medtronic. My only interest is in improved patient outcomes.
Sponsored by
Kyphon™ Balloon Kyphoplasty incorporates technology developed by Gary K. Michelson, M.D.

3. OSTEOPOROSIS
Osteoporosis is a silent disease until it leads to a fracture1
estimated to affect 200 million women1
causes more than 700,000 spinal fractures each year in the U.S.2
Vertebral Compression Fractures (VCFs)
most common osteoporotic fractures affecting 1.4 million people worldwide1
up to two thirds are undiagnosed 2
5-fold increased risk of another fracture within 1 year2
International Osteoporosis Foundation Website. May 2016
Brunton S, Carmichael B, Gold D et al. Vertebral compression fractures in primary care recommendations from a consensus panel. J Fam Pract Sep;54(9):781-8.
Van Meirhaeghe J, Bastian L, Boonen S, et al. A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures: vertebral body kyphosis correction and surgical parameters. Spine (12), pp

4. REDUCED BONE STRENGTH
Approximately one in two women over age 50 will break a bone due to osteoporosis.1
Normal Vertebra
Fractured Vertebra
Normal Bone2
Osteoporotic Bone2
Osteoporosis is “A systemic skeletal condition characterized by decreased bone strength, with reduced bone quantity and decreased bone quality, with resulting increased susceptibility to fracture.” Silverman, et al. Osteoporos Int. 2002;13(11):
National Osteoporosis Foundation website. Accessed May 2016.
Dempster DW, et al. J Bone Miner Res. 1986;1:15-21.

5. HEALTH AND QUALITY OF LIFE
CONSEQUENCES
HEALTH AND QUALITY OF LIFE
VCFs lead to back pain, height loss, kyphosis, and mobility and quality of life impairment.1-3
Health consequences3:
Increased risk of falls and fractures
Increased patient disability
Height loss
Chronic and acute pain
Reduced quality of life
Quality of life consequences3:
Reduced mobility, including slower walking pace and use of walking aids
Loss of self-esteem
Social isolation
Depression
International Osteoporosis Foundation Website. May 2016.
Dohm M, Black C, Dacre A, et al. A randomized trial comparing balloon kyphoplasty and vertebroplasty for vertebral compression fractures (VCFs) due to osteoporosis. AJNR
Brunton S, Carmichael B, Gold D et al. Vertebral compression fractures in primary care recommendations from a consensus panel. J Fam Pract. 2005;54(9):

6. CONSEQUENCES SUBSEQUENT FRACTURE
Once a VCF has occurred, the risk for additional fracture increases.1,2
VCFs, whether clinically apparent or silent, are major predictors of future fracture risk, up to 5-fold for subsequent vertebral fracture.1,2
1. Lindsay R, Silverman S, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001;285(3):
2. Ross P, Davis J, Epstein R, et al., Pre-Existing Fractures and Bone Mass Predict Vertebral Fracture Incidence in Women. Ann Intern Med. 1991;114(11):

7. Mortality rate per 1,000 person
VCF PATIENTS HAVE HIGHER MORTALITY RISK THAN NON-VCF PATIENTS1
“ …Medicare patients with a vertebral fracture had an overall mortality rate that was approximately twice that of the matched controls.”- Lau et al. JBJS 20081
Mortality rate per 1,000 person
years of observation
As estimated with the Kaplan-Meier method, survival rates for patients after being diagnosed with VCFs at three, five, and seven years, were 53.9%, 30.9%, and 10.5%, respectively.
From 1997 through 2004, VCF cohort accumulated a total of 171,444 person years of observation, with an average of 21.2 months per patient while control cohort accumulated a total of 1,109,763 person-years of follow-up, with an average of 31.0 months per person.
By December 31, 2004, a total of 39,707 deaths of patients with a VCF were identified, for an overall death rate of deaths per 1000 person-years of observation. The total number of deaths in the control group was 94,982, a death rate of 85.6 per 1000 person-years of observation.
Overall, without adjustment for differences in comorbidity, the hazard ratio between patients with a VCF and patients with no VCF was Adjustment for the baseline health of the patients lowered the hazard ratio to 1.83.
Study Design: Retrospective data analysis of Medicare claims from 1997 through using Claims records from the 5% Medicare Beneficiary Encrypted File (Patients with VCF = 97,142/ Control = 428,956) .
Limitations: Use of Medicare data was unable to identify the severity of each VCF and number of fracture sustained by patient. Study did not include a comparison of treatment options or efficacy of preventive regimens.
Lau E, Ong K, Kurtz S, et al. Mortality following the diagnosis of a vertebral compression fracture in the Medicare population. J Bone Joint Surg Am Jul;90(7): doi: /JBJS.G

8. A DOWNWARD SPIRAL OF COMPLICATIONS IS ASSOCIATED WITH VCFs7,8,9
Early diagnosis and interventional treatment are important steps to avoiding complications associated with VCFs.1-3
Surgical and non-surgical methods are used to treat VCFs.4- 9
The goals of non surgical management are to reduce pain and improve functional status. However, non-surgical management of VCFs has limited effectiveness.4-9
Mortality
Brunton S, Carmichael B, Gold D et al. Vertebral compression fractures in primary care recommendations from a consensus panel. J Fam Pract Sep;54(9):781 8.
Vedantam R. Management of osteoporotic vertebral compression fractures: a review. Am J Clin Med. 2009;6(4):
Ross PD. Clinical consequences of vertebral fractures. Am J Med. 1997;103(2A):30S-43S.
Berenson J, Pflugmacher R, Jarzem P et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol Mar;12(3):
Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet Mar 21;373(9668):
Boonen S, Van Meirhaeghe J, Bastian L, et al. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-yearresults from a randomized trial. J Bone Miner Res Jul;26(7):
Van Meirhaeghe J, Bastian L, Boonen S, et al. A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures: vertebral body kyphosis correction and surgical parameters. Spine (12), pp
Medtronic Data on File - Tillman J, Shabe P, Rose M, et al. Fracture reduction evaluation study 24-month final clinical study report, August 27, Medtronic Spinal and Biologics Europe BVBA.
Klazen C, Lohle P, de Vries J, et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet Sep 25;376(9746):

9. Clinical data with >1,000 participants and 12+ months follow up

10. Majority of studies show that BKP/VP patients have lower mortality risk (up to 43% lower) than patients treated with non-surgical management at up to 5 years follow up.1-5
Several recent large clinical studies that followed patients for at least 12 months after vertebral compression fracture (VCF) have concluded that mortality rates following VCFs are significantly higher for patients treated conservatively versus VP or BKP, while other studies have concluded no difference. For more information visit
Edidin AA, et al. Spine Aug 1;40(15): doi: PubMed PMID:
Edidin AA, et al. J Bone Miner Res Jul;26(7): doi: /JBMR.353. PubMed PMID:
Chen AT, et al. J Bone Joint Surg Am Oct 2;95(19): doi: /JBJS.K PubMed PMID:
Lange A, et al. Spine Feb 15;39(4): doi: /BRS PubMed PMID:
McCullough BJ, et al. JAMA Intern Med Sep 9;173(16): doi: /jamainternmed PubMed PMID: ; PubMed Central PMCID: PMC

11. TREATMENT CHOICES AND MORTALITY RISK
Patients treated with BKP/VP had:
NO DIFFERENCE
IN MORTALITY RISK AT 1 YEAR5
SIGNIFICANTLY LOWER MORTALITY RISK THAN PATIENTS TREATED WITH NSM AT UP TO 5 YEARS OF FOLLOW UP *1,2,3,4
Edidin et al *
(JBMR 2011)1
n=858,978
Chen et al. *
(JBJS 2013)2
n= 68,752
Lange et al. *
(SPINE 2014)3
n=3,607
BKP: 44% lower mortality risk than NSM
(AHR =0.56, 95% CI 0.55– 0.57)
VP: 24% lower mortality risk than NSM
(4 years) +
BKP: 32.3% lower mortality risk than NSM
(AHR =0.68, 95% CI 0.66– 0.70)
VP: 15.5% lower mortality risk than NSM
(3 years) +
BKP/VP : 43% lower mortality risk than NSM
(AHR = 0.57; 95% CI: 0.48– 0.70)
(5 years) ++
Edidin et al. *
(Spine 2015)4
n=1,038,956
NSM: 55% higher mortality risk than BKP
( AHR = % CI: )
NSM: 25% higher mortality risk than VP
After propen­sity matching, the Kaplan-Meier risk of mortality at 4 years was still found to be greater for the nonoperated cohort.
(AHR 1.62; 95% CI: 1.60–1.64)
(4 years) +
McCullough et al.
(JAMA 2013)5
n=126,392
BKP/VP: Significantly lower mortality risk than NSM
(HR 0.83; 95%CI, )
After propensity score matching to better account for selection bias, 1-year mortality was not significantly different between the groups
(5.2% vs 6.7%)
( HR 0.92; 95% CI, ) (p=0.18)
(1 year) +
BKP/VP (n=182,946)/NSM (n=676,032)
BKP/VP (n=30,503)/NSM (n=38,249)
BKP/VP (n=598)/NSM (n=3,009)
* Adjusted mortality risk (p < ) / AHR = adjusted hazard ratio
+ Retrospective database review of claims data that evaluated the mortality risk for patients with VCFs undergoing different treatment modalities
++ Observational study of claims data that examined the survival of patients treated with BKP/ vertebroplasty (VP) vs NSM with a follow-up time of up to 5 years
BKP/VP (n=216,707)/ / NSM (n=822,249)
BKP/VP (n=10,541)/NSM (n=115,851)
Several recent large clinical studies followed for at least 12 months after VCF have concluded that mortality rates following VCFs are significantly higher for patients treated conservatively versus VP or BKP, while other studies have concluded no difference. For more information, visit
BKP/VP (n=216,707)/NSM (n=822,249)
Edidin AA, et al. Spine Aug 1;40(15): doi: PubMed PMID:
Edidin AA, et al. J Bone Miner Res Jul;26(7): doi: /JBMR.353. PubMed PMID:
Chen AT, et al. J Bone Joint Surg Am Oct 2;95(19): doi: /JBJS.K PubMed PMID:
Lange A, et al. Spine Feb 15;39(4): doi: /BRS PubMed PMID:
McCullough BJ, et al. JAMA Intern Med Sep 9;173(16): doi: /jamainternmed PubMed PMID: ; PubMed Central PMCID: PMC

12. STUDY LIMITATIONS The studies reviewed:
are retrospective database analyses and are prone to selection bias;
have variables that are not captured in the database that may explain mortality effects;
have study designs that cannot demonstrate causality of treatment received with mortality outcomes;
indicate to some extent that BKP (and VP) subjects have better “baseline” health, which may at least partially explain the mortality benefit.

13. UNDERSTANDING the IMPACTs TO the HEALTHCARE SYSTEM

14. PERFORMANCE GAP Under-identification1 Under-treatment1
Many patients who meet guidelines for bone density testing are not tested
Many patients with fractures are not diagnosed as having osteoporosis
Under-treatment1
Most patients with osteoporosis or fractures are not treated to reduce risk of future fractures
Poor compliance and persistence with therapy2,3
An estimated 50% of new osteoporosis medication users continue therapy for a month treatment period
Oral bisphosphonates are frequently taken incorrectly
Cosman F, de Beur SJ , LeBoff MS, Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014; 25(10): 2359–2381.
Rabenda V, Hiligsmann M, Reginster JY. Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin. Pharmacother. 10, 2303–2315 (2009).
Siris E, Selby P, Saag K, Borgström F, Herings R, Silverman S. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe.Am. J. Med. 122, S3–S13 (2009).

15. TREATMENT CONSIDERATIONs
Patients diagnosed with a VCF should also be evaluated for the underlying condition (osteoporosis)
Bone density testing (DXA)
Evaluation for secondary causes
A comprehensive treatment plan may include:
Risk reduction planning and counseling
Calcium and vitamin D supplementation
Pharmacologic therapy
Appropriate exercise once mobility is regained

16. VCFS ARE A FINANCIAL BURDEN TO both PATIENTS AND THE HEALTHCARE SYSTEM
Patients with VCF average 10 days of hospital stay1
The associated pain and disability result in an estimated 150,000 hospitalizations per year2
Cost of $17 billion in 2005; estimated to reach $25.3 billion in 20253
Papaioannou A, Adachi JD , Parkinson W, Stephenson G, Bédard M. Lengthy hospitalization associated with vertebral fractures despite control for comorbid conditions. Osteoporos Int. 2001;12(10):
Chen AT, Cohen DB, Skolasky RL. Impact of nonoperative treatment, vertebroplasty, and kyphoplasty on survival and morbidity after vertebral compression fracture in the medicare population. J Bone Joint Surg Am Oct 2;95(19):
Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, J Bone Miner Res Mar;22(3):

17. TREATING VCF PATIENTS WITH BKP GENERATES LONG-TERM VALUE AND COST EFFECTIVENESS
BKP HAD SIGNIFICANTLY SHORTER LENGTH OF STAY VS NSM
Patients treated with non-surgical
management (NSM) experience a
mean length of stay of 7.38 days
compared to 3.74 days for BKP
patients (p< 0.001)
Based on analysis of 68,752 hospitalized Medicare patients (38,249 NSM;22,817 BKP;7,686 VP).
For patients treated with VP, Length of stay is at 5.73 days (p< 0.001).
In this data analysis, BKP subjects had fewer preexisting conditions at baseline. The rates of infection and neurological compromise among patients who had undergone a vertebral augmentation procedure (either VP or BKP) were not significantly different from the rates among patients who had NSM.
Chen AT, Cohen DB, Skolasky RL. Impact of nonoperative treatment, vertebroplasty, and kyphoplasty on survival and morbidity after vertebral compression fracture in the medicare population. J Bone Joint Surg Am Oct 2;95(19): 17

18. TREATING VCF PATIENTS WITH BKP GENERATES LONG-TERM VALUE AND COST EFFECTIVENESS
BKP HAD GREATER LIKELIHOOD OF ROUTINE DISCHARGES TO HOME VS NSM
BKP is associated with a
greater likelihood of routine
discharge to home
Based on analysis of 68,752 hospitalized Medicare patients (38,249 NSM;22,817 BKP;7,686 VP).
For patients treated with VP, discharges to home is at 39% (p < 0.001).
In this data analysis, BKP subjects had fewer preexisting conditions at baseline. The rates of infection and neurological compromise among patients who had undergone a vertebral augmentation procedure (either VP or BKP) were not significantly different from the rates among patients who had NSM.
Chen AT, Cohen DB, Skolasky RL. Impact of nonoperative treatment, vertebroplasty, and kyphoplasty on survival and morbidity after vertebral compression fracture in the medicare population. J Bone Joint Surg Am Oct 2;95(19): 18

19. TREATING VCF PATIENTS WITH BKP GENERATES LONG-TERM VALUE AND COST EFFECTIVENESS
BKP HAD SIGNIFICANTLY LOWER READMISSION RATE VS NSM
62% of Medicare inpatients
treated with NSM are readmitted to the hospital within 30 days compared to 35% for BKP (p< 0.001)
Based on analysis of 68,752 hospitalized Medicare patients (38,249 NSM;22,817 BKP;7,686 VP).
For patients treated with VP, readmission rate is at 52.4% (p < 0.001).
In this data analysis, BKP subjects had fewer preexisting conditions at baseline. The rates of infection and neurological compromise among patients who had undergone a vertebral augmentation procedure (either VP or BKP) were not significantly different from the rates among patients who had NSM.
Chen AT, Cohen DB, Skolasky RL. Impact of nonoperative treatment, vertebroplasty, and kyphoplasty on survival and morbidity after vertebral compression fracture in the medicare population. J Bone Joint Surg Am Oct 2;95(19): 19

20. TREATING PATIENTS WITH KYPHON™ BALLOON KYPHOPLSTY

21. Vertebral Compression fractures
Common signs & Patient Selection
Common Signs
Sudden onset of back pain without obvious explanation (acute)
Loss of height
Kyphosis
Protruding abdomen (chronic)
Patient Selection
Activity-related axial pain corresponding to level of recent compression fracture
Pain decreases or disappears when lying down and/or sitting still
Tenderness over appropriate level of fracture
Complete neurological exam and radiographic evaluations
Suzuki, et al. Eur Spine J

22. Vertebral Compression fractures
Treatment Algorithm
Brunton, et al. J Fam Practice

23. Minimally invasive, short procedure (typically around an hour)
Orthopedic balloons are used to gently elevate the fractured vertebra in an attempt to return it to the correct position
The cavity is then filled with bone cement, creating an internal cast to support the surrounding bone
Can be performed under general or local anesthesia, either in hospital or physician office setting
Can stabilize painful VCFs, reduce back pain, and restore vertebral body height1
There are risks associated with the procedure (e.g., cement extravasation), including serious complications, and though rare, some of which may be fatal. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events, and methods of use, please reference the devices’ Instructions for Use included with the product.
Boonen S, et al. J Bone Miner Res. 2011;26(7):

24. Kyphon™ Balloon Kyphoplasty for Vertebral Compression fractureS
Effectiveness EVIDENCE
Better clinical results compared to non-surgical management
Rapid and sustained pain relief1
3X greater pain reduction at 1 week vs. non-surgical management (NSM) (46% BKP vs. 15% NSM, P≤0.0001)2
Enhanced quality of life1
4X greater improvement in quality of life at 1 month vs. NSM (P≤0.0001)2
Improved mobility1
5 fewer days of restricted activity at 1 month (P≤0.0001)1,2
Less use of narcotic analgesics1
Fracture Reduction Evaluation (FREE) 24-month study—70% of patients treated with BKP were no longer taking pain medications at 6 months vs. 57% NSM (P=0.042)
Comparable safety results vs. NSM1
Similarities in overall frequencies of adverse events and serious adverse events between treatment groups during the 24-month FREE study1
Boonen S, et al. J Bone Miner Res. 2011;26(7):
Tillman J, et al. Fracture Reduction Evaluation Study 24-month final clinical study report, August 27, Medtronic Spinal and Biologics Europe BVBA.

25. TREATING VCF PATIENTS CAN HAVE A POSITIVE IMPACT ON HEALTHCARE COST-SAVING INITIATIVES
($275K cost savings is based on 100 patients)
1. Hospital Adjusted Expenses per Inpatient Day. Accessed April 13, 2015.
2. Medtronic Data on File. Estimate as of December 2014.

26. Kyphon™ Balloon Kyphoplasty for Vertebral Compression fractureS
Effectiveness EVIDENCE
Does treatment increase the risk of subsequent fractures?
Patients treated with Kyphon™ Balloon Kyphoplasty showed no additional risk of subsequent fractures vs. those treated with non-surgical management over the course of 2 years.1,2
There was no statistically significant difference in the number of patients with new radiographic fractures between the groups at 24 months.1,2
100% 0%
47.5%
44.1%
BKP
NSM
It is worth noting that this study was not powered to detect
differences in fractures between the two groups.
Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet Mar 21;373(9668):
Boonen S, Van Meirhaeghe J, Bastian L, et al. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial. J Bone Miner Res Jul;26(7):

39. **RFA may have a benefit in providing some pain relief quickly, while allowing time for RT to provide additional relief.

49. Thank You.