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The Effectiveness of Intraosseous Basivertebral Nerve
Radiofrequency Ablation for the Treatment of Vertebrogenic
Low Back Pain: An Updated Systematic Review with Single-Arm
Meta-analysis
Aaron Conger, DO, Taylor R. Burnham DO, MS, Tyler Clark, MD,
Masaru Teramoto, PhD, MPH, PStatV
R, and Zachary L. McCormick ,MD
Division of Physical Medicine and Rehabilitation, University of Utah, Salt Lake City, Utah, USA
Correspondence to: Aaron Conger, DO, Department of Physical Medicine and Rehabilitation, University of Utah, 590 Wakara Way, Salt Lake
City, UT 84108, USA. Tel: 801.587.5458; Fax: 801.587.7111; E-mail: aaron.conger@hsc.utah.edu.
Funding sources: This investigator-initiated review was supported by a grant from Relievant MedSystems (paid directly to the University of Utah). The
sponsor had no role in the design or conduct of the review or in the approval of the final manuscript. The protocol, search, data extraction, and statisti-
cal analysis were developed and performed independently.
Disclosures and Conflicts of interest: Dr. Aaron Conger and Dr. Zachary L. McCormick have received investigator-initiated research funding from
Relievant MedSystems (paid directly to the University of Utah).
Supplement sponsorship: This article appears as part of the supplement entitled “Vertebrogenic Pain and Basivertebral Nerve Radiofrequency
Ablation”sponsored by Relievant Medsystems Inc.
Study registration: PROSPERO (ID:CRD42020192001).
Received on 9 February 2022; revised on 18 April 2022; Accepted on 18 April 2022
Abstract
Objective. To provide an estimate of the effectiveness of basivertebral nerve (BVN) radiofrequency ablation (RFA) to
treat vertebrogenic low back pain (LBP). Design. Systematic review with single-arm meta-analysis. Population.
Persons 18 years of age with chronic LBP associated with type 1 or 2 Modic changes. Intervention. Intraosseous
BVN RFA. Comparison. Sham, placebo procedure, active standard care treatment, or none. Outcomes. The proportion
of patients treated with BVN RFA who reported 50% pain score improvement on a visual analog scale or numeric
rating scale. The main secondary outcome was 15-point improvement in Oswestry Disability Index score. Methods.
Three reviewers independently assessed articles published before December 6, 2021, in MEDLINE and Embase. The
Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to evaluate
the overall quality of evidence. Results. Of the 856 unique records screened, 12 publications met the inclusion criteria,
representing six unique study populations, with 414 participants allocated to receive BVN RFA. Single-arm meta-
analysis showed a success rate of 65% (95% confidence interval [CI] 51–78%) and 64% (95% CI 43–82%) for 50%
pain relief at 6 and 12 months, respectively. Rates of 15-point Oswestry Disability Index score improvement were
75% (95% CI 63–86%) and 75% (95% CI 63–85%) at 6 and 12 months, respectively. Conclusion. According to GRADE,
there is moderate-quality evidence that BVN RFA effectively reduces pain and disability in most patients with vertebro-
genic LBP. Further high-quality studies will likely improve our understanding of the effectiveness of this procedure.
Key Words: Endplate; Vertebrogenic, Discogenic; Modic; Ablation
Introduction
Intraosseous basivertebral nerve (BVN) radiofrequency
ablation (RFA) has gained attention as a target-specific
treatment for pain arising from pathological degeneration
of the vertebral endplates (VEPs) of the lumbosacral spine.
At lumbar levels, the BVN is a paired branch of the bilat-
eral sinuvertebral nerves that passes through the basiverte-
bral foramen at the posterior aspect of the vertebral body
V
CThe Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/
by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way,
and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com S50
Pain Medicine, 23(S2), 2022, S50–S62
https://doi.org/10.1093/pm/pnac070
Review Article
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to provide sensory innervation to the vertebral body and
VEPs. Effective neurotomy of the BVN can be accom-
plished through careful transpedicular access under either
fluoroscopy or computed tomography (CT) guidance, fol-
lowed by ablation at a location 30–50% of the sagittal
plane distance from the posterior cortex of the vertebral
body [1,2]. Since 2017, this treatment has been studied
exclusively in populations believed to have pain arising
from pathologically degenerated VEPs as evidenced by
Modic 1 (MC1) and 2 changes (MC2) on magnetic reso-
nance imaging (MRI) [1,3–12].
Although BVN RFA is a relatively new treatment,
studies investigating the pathological degeneration of the
discovertebral complex began in the early 1990s.
Initially, scientists postulated that the BVN might be im-
plicated in nociception in some cases of chronic low back
pain (LBP) after histological studies demonstrated that
the BVN contained numerous neuropeptide Y– and PGP
9.5–positive nerve fibers [13,14]. The case for VEP-
driven pain was further strengthened when immunohisto-
chemical analysis of the BVN demonstrated an abun-
dance of nerve fibers in the BVN that stained positive for
substance P, CGRP, and PGP 9.5 [15,16]. Compared
with controls, surgical specimens from patients with a
history of chronic LBP and advanced disc degeneration
were noted to have increased nociceptor density in the
endplate region and adjacent vertebral body. This same
pattern was observed in surgical specimens taken from
patients with a history of “discogenic” LBP, where
greater concentrations of PGP 9.5– and tumor necrosis
factor (TNF)–immunoreactive cells near the VEPs were
found compared with controls [17]. These histological
findings were strongly associated with MC1 and MC2
findings on MRI.
Modic type 1 and 2 marrow changes are a radio-
graphic manifestation of the underlying inflammatory re-
sponse and fatty infiltration, respectively. These occur in
the presence of prolonged mechanical stress and endplate
failure, coupled with the ensuing chemical sensitization
from leakage of proinflammatory cytokines from the in-
tervertebral disc [25]. The epidemiology and clinical sig-
nificance of MC1 and MC2 lesions have been discussed
and debated ad nauseum [2,18–24]. Modic changes are
observed in the context of advanced disc degeneration or
disc herniation [18,19], but even stronger associations
exist with endplate defects in large population-based co-
hort studies [20,21]. Endplate injuries can be classified
according to their pathoanatomic features: 1) avulsion of
annulus fibrosus (“annulus”) fibers from their insertion
at the cartilage endplate (tidemark avulsion), 2) separa-
tion of endplate from the bone (cartilage endplate avul-
sion), 3) degeneration of the bone–annulus interface (rim
degeneration), and 4) traumatic or erosive ingrowth of
nucleus pulposis material through the endplate (nodal)
[22]. Although of unclear clinical significance, these
descriptors help paint a more detailed picture of the disc–
endplate relationship. Endplate injuries are likely the
predisposing event that, in a subset of individuals, results
in chronic inflammation, high bone turnover, and fatty
infiltrative changes that can be observed with conven-
tional T1- and T2-weighted MRI sequences [23]. This
cascade of events can culminate in what is often referred
to as “vertebrogenic” LBP, with nociception transmitted
predominantly via the BVN.
Objectives and Rationale
Given the recent increase in studies investigating the
treatment of vertebrogenic LBP, the present systematic
review was performed to provide an updated estimate of
the effectiveness of BVN RFA for the treatment of this
condition. We also calculate the aggregate rates of treat-
ment success defined by clinically important pain and
functional improvement observed thus far in published
clinical trials and cohort studies.
Methods
Protocol and Registration
This systematic review is an update of a prior systematic
review for which the protocol was registered with
PROSPERO (ID:CRD42020192001) on July 14, 2020.
No changes were made to the review methodology, but
to avoid redundancy, a 15-point Oswestry Disability
Index (ODI) threshold was chosen to measure functional
improvement [24]. A 15-point ODI improvement is a ro-
bust threshold that exceeds the known minimum clini-
cally important difference for chronic LBP [25,26]. The
methods and results are reported in accordance with the
2020 Preferred Reporting Items for Systematic Reviews
and Meta-Analysis (PRISMA) guidelines [27].
Eligibility Criteria
Population
The population of interest was adults 18 years of age or
older with chronic LBP associated with MC1 and MC2
changes on MRI.
Intervention
The intervention considered was intraosseous BVN RFA.
Comparison
Sham, placebo procedure, active standard care treatment,
or none.
Outcome
The primary outcome considered for this review was the
proportion of individuals with 50% pain improvement
on the visual analog scale (VAS) or numeric rating scale
(NRS). Secondary outcomes included 15-point im-
provement in ODI score and 2-point improvement in
NRS score. Outcomes reported at any time point were
included.
Basivertebral Nerve Ablation Systematic Review S51
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Studies
Both randomized controlled trials (RCTs) and observational
study designs (nonrandomized comparative studies and sin-
gle-group observational studies) were included. Non–English
language articles and case reports were excluded. No restric-
tions were placed on the publication date.
Information Sources and Search Strategy
The databases MEDLINE and Embase were searched
from inception up through December 6, 2021.
MEDLINE was queried with the following terms:
("Basivertebral nerve ablation"[tiab] OR "BVN abla-
tion"[tiab] OR "catheter ablation"[MeSH Terms] OR
verteblation[tiab] OR "radiofrequency neurotomy"[tiab]
OR "radiofrequency neurotomies" [tiab] OR "radiofre-
quency ablation"[tiab] OR "radiofrequency ablations"
[tiab]) AND ("low back pain"[mesh] OR "low back
pain"[tiab] OR CLBP[tiab] OR vertebrogenic[tiab] OR
"modic change*"[tw] OR "disc degeneration"[All Fields]
OR "endplate degeneration"[tiab] OR "endplate inflam-
mation"[tiab] OR "disc inflammation"[tiab] OR "fatty
bone marrow"[tiab] OR "fibrous bone marrow"[tiab]
OR "endplate disruption"[tiab]).
Embase was queried with the following terms:
(
0
radiofrequency ablation
0
/exp OR (
0
basivertebral nerve
ablation
0
:ab,ti,kw OR
0
bvn ablation
0
:ab,ti,kw OR
0
catheter ablation
0
:ab,ti,kw OR verteblation:ab,ti,kw OR
0
radiofrequency neurotomy
0
:ab,ti,kw OR
0
radiofrequency
neurotomies
0
:ab,ti,kw OR
0
radiofrequency abla-
tion
0
:ab,ti,kw OR
0
radiofrequency ablations
0
:ab,ti,kw
OR
0
radio frequency ablation
0
:ab,ti,kw OR
0
rfa therapy-
:ab,ti,kw OR
0
rfa therapies
0
:ab,ti,kw)) AND (
0
low back
pain
0
/exp OR (
0
low back pain
0
:ab,ti,kw OR clbp:ab,ti,kw
OR vertebrogenic:ab,ti,kw OR
0
modic change*
0
:ab,ti,kw
OR
0
disc degeneration
0
:ab,ti,kw OR
0
endplate degenera-
tion
0
:ab,ti,kw OR
0
endplate inflammation
0
:ab,ti,kw OR
0
disc inflammation
0
:ab,ti,kw OR
0
fatty bone mar-
row
0
:ab,ti,kw OR
0
fibrous bone marrow
0
:ab,ti,kw OR
0
endplate disruption
0
:ab,ti,kw)).
An experienced librarian developed the search strategy.
One author (AC) performed the search, and the search
was confirmed for accuracy and reproducibility by a sec-
ond author (TC). Additional eligible records were sought
from the cited references of retrieved publications.
Study Selection
Two authors (AC and TC) independently assessed each
abstract for eligibility. Any disagreements about inclu-
sion were resolved by a third reviewer (ZM).
Publications selected for full-text review were further
assessed for inclusion by two authors (AC and TC), with
disagreements resolved by a third reviewer (ZM).
Data Items and Collection
The following information was extracted from each
study: 1) outcome measures for VAS/NRS and ODI, as
well as any information related to pain medication usage
or healthcare utilization; 2) bibliographic details; 3)
study design; 4) selection criteria; 5) technical details of
the procedure; and 6) funding and author disclosures. If
data considered critical to the research questions were
missing from included studies, attempts were made to
contact author groups to obtain this information.
Risk of Bias and Methodological Assessment
The quality of evidence across outcomes was evaluated
with the Grades of Recommendation, Assessment,
Development and Evaluation (GRADE) system [32].
Accordingly, risk of bias, imprecision, inconsistency, in-
directness, and publication bias were all assessed.
Disagreements about determinations of evidence quality
according to GRADE were resolved by consensus deci-
sion. Our previous systematic review included a GRADE
evidence profile based on calculations of between-group
success measurements for the included RCTs, and this
was again planned for the present review.
Summary Measures and Synthesis of Results
The primary outcome of interest was the percentage of
participants reporting 50% pain improvement, and the
main secondary outcome of interest was 15-point ODI
improvement after BVN RFA. A between-group compar-
ison of categorical success rates with calculated relative
risk and risk difference was planned. Conventional pair-
wise and single-arm meta-analysis was also planned for
this review if the collected data were found to be suffi-
cient for such analysis.
Meta-analyses were planned to examine the following
binary outcome variables (yes/no) over time points of 6
months, 12 months, 24 months, and 60 months: 1) pro-
portions of patients reporting 15-point ODI improve-
ment and 2) proportions of patients reporting 50%
NRS/VAS improvement. Proportions and their standard
errors of the included studies were used to calculate a
pooled effect size (ES) and its 95% confidence interval
(CI) in each meta-analysis. A random-effects model was
used for all meta-analyses, as heterogeneity was expected
in observational studies [28], which was also verified by
heterogeneity and I
2
statistics [29]. Specifically, the cal-
culations were performed with (inverse-variance)
Freeman-Tukey double arcsine transformation [30,31]
and the exact CIs for the ESs of individual studies [32].
Forest plots were produced for the data at 6 months and
12 months to illustrate the ESs of individual studies, as
well as the pooled ES from those studies [28].
Furthermore, line graphs were constructed to visualize
ESs over the time points. Publication bias was assessed
with Egger’s test [33,34]. Funnel plots were not used, as
the number of included studies for each meta-analysis
S52 Conger et al.
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was fewer than 10, which is the recommended minimum
number of studies for the assessment of publication bias
with a funnel plot [35]. Lastly, sensitivity analysis was
conducted to assess the between-study heterogeneity and
impact of an individual study on the pooled ES; this was
done through the leave-one-out approach, which recalcu-
lated the pooled ES after a study was omitted, one by one
[28,29]. All of the analyses were performed in Stata 17.0
(StataCorp LLC, College Station, TX, USA).
Results
A total of 856 unique records were identified from the
search (Figure 1). After abstract screening for relevant pub-
lications, 12 full-text articles were assessed and deemed eli-
gible for inclusion. There were no disagreements among
reviewers about study inclusion. These included one RCT
comparing BVN RFA with sham, with outcomes reported
at up to 1, 2, and 5 years [4,7,9,10]; one RCT comparing
BVN RFA with standard care treatment, with outcomes
reported at up to 3, 6, 12, and 24months [8,11,36]; and
four single-group cohort studies, with outcomes reported
between 3 and 12 months [1,3,5,6,12].
Study Characteristics
The main characteristics of the included studies are summa-
rized in Table 1. From 2017 to 2021, a total of 414 partici-
pants were allocated to receive BVN RFA in two RCTs and
four single-group cohort studies [1,3,5,7,11,12,36].
Participants in all reviewed studies were adults with chronic
LBP for 6monthswithMC1andMC2changeswithinat
least one of the L3–S1 vertebral bodies. In addition to MC1
and MC2 changes on MRI, participants in the cohort study
by De Vivo et al. underwent SPECT/CT and CT-guided me-
dial branch blocks to exclude lumbar facet joint pain [1].
Records identified from:
Databases (n = 894)
Registers (n = 0)
Records removed before
screening:
Duplicate records removed
(n = 38)
Records marked as ineligible
by automation tools (n =0)
Records removed for other
reasons (n =0)
Records screened
(n = 856)
Records excluded
(n = 844)
Reports sought for retrieval
(n = 12)
Reports not retrieved
(n = 0)
Reports assessed for eligibility
(n = 12) Reports excluded: 0
New studies included in review
(n = 2)
Reports of new included studies
(n = 2)
Identification of new studies via databases and registers
Identification
Screening
Included
Total studies included in review
(n = 6)
Reports of total included studies
(n = 12)
Studies of unique
populations included in
previous version of
review (n = 4)
Reports of studies
included in previous
version of review (n = 7)
Previous studies
Figure 1. PRISMA 2020 flow diagram for updated systematic reviews.
Basivertebral Nerve Ablation Systematic Review S53
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Table 1. Study characteristics
Author, Year Design
Study
Size Inclusion Criteria
Mean/Median
Ages of
Participants (Range)
Participant
Duration
of Pain Intervention
Targeting
Success (Based
on Post-Ablation MRI)Adverse Events
Author
Disclosures
Fischgrund 2018* RCT 225 randomized, 147
received BVN RFA.
128 analyzed in PP
population (ex-
cluded n ¼19
for targeting/access
failure or protocol
noncompliance).
CLBP 6 months despite
conservative treatment,
Modic 1 or 2 changes from
L3–S1, minimum ODI 30,
minimum VAS 4 mm
Mean 46.9
(26–69)
6–12 months 4.1%,
1–2 years 10.2%,
2–3 years 6.8%,
3–5 years 12.2%,
5 years 66.7%
Fluoroscopically
guided BVN RFA,
85C bipolar abla-
tion for 15 minutes
40–60% from pos-
terior wall
95% n ¼1 nerve root injury
(sham group), n ¼1
vertebral compression
fracture (sham group),
n¼7 lumbar radiculli-
tis, retroperitoneal
hemorrhage (n ¼1),
and transient motor or
sensory deficits, all re-
solved with supportive
care.
Industry
funded
Fischgrund 2019* SGOS 128 at 18 months and
106 at 24 months
" " " " " No delayed adverse
events
Industry
funded
Fischgrund 2020* SGOS 100 " " " " " No delayed adverse
events
Industry
funded
Markman 2019* PSA 224 " " " " " No delayed adverse
events
Industry
funded
Khalil 2019
†
RCT 140 randomized, 51
received BVN RFA
CLBP 6 months despite
conservative treatment,
Modic 1 or 2 changes from
L3–S1, minimum ODI 30,
minimum VAS 4 cm
Mean 50.0
(26–70)
6–12 months 5.8%,
1–2 years 2.9%,
2–3 years 11.5%,
3–5 years 12.5%,
5 years 62.7%
Fluoroscopically
guided BVN RFA,
85C bipolar abla-
tion for 15 minutes
30–50% from pos-
terior wall
96% n ¼15, incisional pain,
leg pain/paresthesia,
back pain in a new lo-
cation, urinary reten-
tion, and lateral
femoral cutaneous
neurapraxia.
Industry
funded
Smuck 2021
†
RCT 66 original RFA arm,
61 crossover from
standard-care arm
treated with BVN
RFA
at average
6.3 months
" " " " 97% No delayed adverse
events
Industry
funded
Koreckij 2021
†
SGOS 58 original BVN RFA
arm
" " " " " No delayed adverse
events
Industry
funded
Becker 2017 SGOS 16 CLBP 6 months, Modic 1
or 2 changes from L3–S1
or positive provocation
discography
Mean 48.0
(34–66)
Not reported Fluoroscopically
guided BVN RFA
(n ¼16), 85C bi-
polar ablation for
15 minutes “at least
10 mm anterior to
the posterior wall”
91% n ¼4, lumbar pain, but-
tock pain, dysesthesia,
and transient numb-
ness, resolved with
pain medications.
Industry
funded
Trumees 2019 SGOS 28 97%
(continued)
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Table 1. continued
Author, Year Design
Study
Size Inclusion Criteria
Mean/Median
Ages of
Participants (Range)
Participant
Duration
of Pain Intervention
Targeting
Success (Based
on Post-Ablation MRI)Adverse Events
Author
Disclosures
CLBP 6 months, Modic 1
or 2 changes from L3–S1,
minimum ODI 30, mini-
mum VAS 4 cm
Mean 45.2
(SD 8.89)
1–2 years 10.7%,
2–3 years 14.3%,
3–5 years 0%,
5 years 75.0%
Fluoroscopically
guided BVN RFA
(n ¼47), 85C bi-
polar ablation for
15 minutes 30–
50% from poste-
rior wall
n¼3, 1 aborted proce-
dure due to inability to
access, 2 leg pain
events due to pedicle
breach
Industry
funded
Macadaeg 2020
‡
SGOS 47 " Median 45.0
(25–66)
1–2 years 14.9%,
2–3 years 10.6%,
3–5 years 2.1%,
5 years 72.3%
" 96% n ¼2, potential pedicle
breach and associated
radiculitis, resolved
with oral medications
Industry
funded
De Vivo 2021 SGOS 56 CLBP 6 months despite
conservative treatment
6 weeks, Modic 1 or 2
changes from L3–S1
Median 43.0
(38–52)
Not reported CT-guided BVN RFA
(n ¼56), core tem-
perature 77C, au-
tomatically stopped
when the proximal
thermocouple
reached 50C, tar-
geted 50% distance
from the posterior
wall.
100% None None
Fishchenko 2021 SGOS 19 CLBP 6 months despite
conservative treatment,
Modic 1 or 2 changes from
L3–S1, minimum ODI 30,
minimum VAS 4 mm
Mean 52.6
(SD 6.9)
1–2 years 73.7% ,
5 years 26.3%
Fluoroscopically
guided BVN RFA
(n ¼19), 85C ab-
lation for
15 minutes 40–
50% distance from
posterior wall
Not reported n ¼1, arterial injury of
the “lumbalis sinistra”
causing a hematoma
within the iliospoas
with associated plexi-
tis, treated with endo-
vascular embolization
None
SGOS¼single-group observational study; PP¼per protocol; PSA¼post-hoc secondary analysis; SD¼standard deviation; CLBP¼chronic low back pain.
Multiple reports from the same population at various time points. Results of the per protocol analysis shown.
†
Multiple reports from the same population at various time points up to 12 months for the original BVN RFA arm and up to 6months for the crossover cohort. Results of the per protocol analysis shown.
‡
Multiple reports from the same population. Truumees et al. reported on the first 28 patients.
Basivertebral Nerve Ablation Systematic Review S55
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Some studies specifically excluded individuals with disc pro-
trusions >5 mm, spondylolisthesis >2 mm, and significant
depression (Beck Depression Inventory >24) [3,5,7,11].
All studies excluded individuals with clinical evidence of
symptomatic spinal stenosis or radicular pain. The majority
of study participants were Caucasian, nonobese, college
educated, and employed [3,7,11]andwereintheir
mid-40s to early 50s [1,3,5,7,11,12]. Most study partici-
pants reported having experienced pain for 5years (62–
72%) [3,7,11], but in one study, 74% of participants
reported a duration of pain between 1 and 2 years [5]. Prior
treatment, where described, included opioid use (32–24%),
spinal injections (61–70%), lumbosacral or sacroiliac joint
RFA (16%), chiropractic care (42%), and physical therapy
(70%) [3,7,11]. Bipolar RFA was performed in all studies
with either fluoroscopic [3,5,7,11,12] or CT guidance [1]
targeting the intraosseous BVN at a point 40–60% from the
posterior wall [7] or 30–50% from the posterior wall [1,
3,5,11]. Patient-reported outcome measures were
reported between 3 and 60 months and included VAS/
NRS, ODI, Short Form 36 (SF-36), EuroQuol 5
Dimensions (EQ5D-5L), healthcare utilization, and opi-
oid use.
Synthesis of Results
Responder rates for VAS and ODI at various thresholds
are presented in Table 2. As only two RCTs (one
sham-controlled trial and one active treatment–controlled
trial) have been performed, conventional pairwise meta-
analysis was not performed. Instead, a single-arm meta-
analysis of outcomes after treatment with BVN RFA was
performed to examine the percentage of responders, de-
fined by the 50% VAS/NRS and 15-point ODI im-
provement thresholds at 6 and 12 months (Figures 2 and
3). For 50% pain improvement at 6 and 12 months, the
calculated success rates were 65% (95% CI 51–78%) and
64% (95% CI 43–82%), respectively. Rates of 15-point
ODI improvement were 75% (95% CI 63–86%) and
75% (95% CI 63–85%) at 6 and 12 months, respectively.
Figures 4 and 5illustrate these same proportions at 6, 12,
24, and 60months longitudinally. Meta-analysis was also
performed to calculate the success rates based on an inten-
tion-to-treat analysis (including lost to follow-up, protocol
deviations, targeting failure, etc.) for the RCTs and a
“worst-case” scenario (unreported patients were categori-
cal failures) for cohort studies, which demonstrated
slightly lower success rates for pain and functional
Table 2. Pain reduction and functional improvement
Author, Year NRS/VAS Responder Percentage (95% CI) ODI Responder Percentage (95% CI)
Fischgrund 2018* 6 months: 50% VAS reduction 46% (37–55%)
§
,
2.0-cm VAS reduction 62% (53–70%)
§
12 months: 50% VAS reduction 41% (32–50%)
§
,
2.0-cm VAS reduction 60% (51–69%)
§
6 months: 15-point ODI reduction 57%
(48–66%)
§
12 months: 15-point ODI reduction 58% (49–67%)
§
Fischgrund 2019* 24 months: 50% VAS reduction 46% (37–55%)
§
,
2.0-cm VAS reduction 67% (58–76%)
§
24 months: 15-point ODI reduction 55% (47–64%)
§
Fischgrund 2020* 60 months: 50% VAS reduction 66% (57–75%),
2.0-cm VAS reduction 88% (82–94%)
60 months: 15-point ODI reduction 77/100, 77% (69–85%)
Markman 2019* Not reported Not reported
Khalil 2019
†
3 months: 50% VAS reduction 63% (49–76%)
§
,
2.0-cm VAS reduction 73% (60–85%)
3 months: 20-point ODI reduction 63%
(49–76%)
Smuck 2021
†
6 months, BVN RFA arm: 50% VAS reduction 62%
(48–74%)
§
,2.0-cm VAS reduction 75% (64–86%)
12 months, RFA arm: 50% VAS reduction 64%
(51–76%), 2.0-cm VAS reduction 79% (68–89%)
6 months, crossover arm: 50% VAS reduction 66%
(52–78%), 2.0-cm VAS reduction 74% (63–85%)
6 months, RFA arm: 15-point ODI reduction 67% (55–79%)
12 months, RFA arm: 15-point ODI reduction 69% (57–
80%)
6 months, crossover arm: 15-point ODI reduction 72% (61–
84%)
Koreckij 2021
†
24 months: 50% VAS reduction 72% (61–84%)
§
,
2.0-cm VAS reduction 79% (69–90%)
24 months: 15-point ODI reduction 77% (66–88%)
Becker 2017 12 months: 50% VAS reduction 38% (15–65%)
§
,
2.0-cm VAS reduction 50% (26–75%)
§
12 months: 15-point ODI reduction 63% (35–85%)
§
Macadaeg 2020
‡
12 months: 50% VAS reduction 67% (52–80%)
§
,
2.0-cm VAS reduction 80% (63–89%)
12 months: 15-point ODI reduction 89% (76–96%)
De Vivo 2021 12 months: 50% VAS reduction 90% (79–97%)
§
,
2.0-cm VAS reduction 96% (92–100%)
12 months: 15-point ODI reduction 82% (69–92%)
§
Fishchenko 2021 12 months: 50% VAS reduction 84% (60–97%) 12 months: 15-point ODI reduction 84% (63–97%)
§
SGOS¼single group observational study, PSA ¼post-hoc secondary analysis.
Multiple reports from the same population at various time points. Results of the per protocol analysis shown.
†
Multiple reports from the same population at various time points up to 12 months for the original BVN RFA arm and up to 6months for the crossover cohort.
Results of the per protocol analysis shown.
‡
Truumees et al. reported on the first 28 patients from this study in 2019.
§
Exact threshold unpublished. Data requested and obtained from the study investigators.
S56 Conger et al.
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improvement: At 6, 12, 24, and 60months 61% (95% CI
48–74%), 59% (95% CI 40–77%), 49% (95% CI 43–
56%), and 50% (95% CI 41–58%) of participants
reported 50% pain improvement. Rates of 15-point
ODI improvement at these same time points were 71%
(95% CI 59–82%), 70% (95% CI 57–81%), 57% (95%
CI 50–64%), and 57% (95% CI 49–65%).
GRADE Quality Assessment
As no new RCTs are included in this updated systematic
review, an updated GRADE evidence profile is not pre-
sented, but GRADE judgments are described narratively.
The evidence from these two RCTs was downgraded
from “high quality” because of the risk of bias in the
form of selective outcome reporting and the inability to
blind participants effectively. The possibility of publica-
tion bias was also considered, given that the majority of
studies have been industry funded [3,7,11,12]; how-
ever, two recently performed independent studies have
shown similar results [1,5]. According to GRADE, there
is moderate-quality evidence that intraosseous BVN RFA
effectively reduces LBP and related disability in those
with vertebrogenic LBP, compared with sham RFA [7]
and continued standard care treatment [11].
Publication Bias and Sensitivity Analysis
According to Egger’s tests, there was no evidence of seri-
ous publication bias in the meta-analysis on the propor-
tions of patients reporting 15-point ODI improvement
at 6 months or 12 months (P¼0.802 and 0.756, respec-
tively) or on the proportions of patients reporting 50%
NRS/VAS improvement at 6 months or 12 months
(P¼0.409 and 0.369, respectively). The sensitivity anal-
ysis showed that the point estimate and CI of the pooled
ES from all meta-analyses did not change substantially
after exclusion of any individual study. Omitting the
study by Fischgrund (2018) for the analysis on 15-point
ODI improvement at 6 months and 12 months would
have resulted in the pooled ESs of 0.78 (original
ES ¼0.75) and 0.79 (original ES ¼0.75), respectively.
Likewise, omitting the study by Macadaeg (2020) at
6 months and 12 months would have resulted in the
pooled ESs of 0.70 (original ES ¼0.75) and 0.71 (original
ES ¼0.75), respectively. However, all of the recalculated
95% CIs for the pooled ES largely overlapped with each
other. In terms of the analysis for 50% NRS/VAS im-
provement, all of the recalculated point estimates of the
ESs (after omission of any individual study) were very
close to the original ESs of 0.65 and 0.64 at 6 months
and 12 months, respectively, with substantial overlap of
CIs.
At 6 months
Fischgrund 2018†
Smuck 2021 (BVN RFA Arm)†
Smuck 2021 (crossover cohort)
Macadaeg 2020†
Becker 2017†
De Vivo 2021†
Fishchenko 2021
Subtotal
At 12 months
Fischgrund 2018†
Smuck 2021 (BVN RFA Arm)
Macadaeg 2020
Becker 2017†
De Vivo 2021†
Fishchenko 2021
Subtotal
Study
0.46 (0.37, 0.55)
0.62 (0.48, 0.74)
0.66 (0.52, 0.78)
0.67 (0.52, 0.80)
0.38 (0.15, 0.65)
0.88 (0.76, 0.96)
0.84 (0.60, 0.97)
0.65 (0.51, 0.78)
0.41 (0.32, 0.50)
0.64 (0.51, 0.76)
0.69 (0.53, 0.82)
0.25 (0.07, 0.52)
0.90 (0.79, 0.97)
0.84 (0.60, 0.97)
0.64 (0.43, 0.82)
ES (95% CI)
0.46 (0.37, 0.55)
0.62 (0.48, 0.74)
0.66 (0.52, 0.78)
0.67 (0.52, 0.80)
0.38 (0.15, 0.65)
0.88 (0.76, 0.96)
0.84 (0.60, 0.97)
0.65 (0.51, 0.78)
0.41 (0.32, 0.50)
0.64 (0.51, 0.76)
0.69 (0.53, 0.82)
0.25 (0.07, 0.52)
0.90 (0.79, 0.97)
0.84 (0.60, 0.97)
0.64 (0.43, 0.82)
ES (95% CI)
0.25 .5 .75 1
Pro
p
ortion
Proportions of patients reporting ≥50% NRS/VAS improvement at six and 12 months
Figure 2. Proportions of patients reporting 50% NRS/VAS improvement at 6 and 12 months. †Exact threshold unpublished, data
requested and obtained from the study investigators.
Basivertebral Nerve Ablation Systematic Review S57
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Discussion
This updated systematic review identified several new
publications that reported on the long-term effectiveness
of BVN RFA. No new randomized trials were identified;
however, substantially more data are now available to
describe the short-, medium-, and long-term success rates
At 6 months
Fischgrund 2018†
Smuck 2021 (BVN RFA Arm)
Smuck 2021 (crossover cohort)
Macadaeg 2020
Becker 2017†
De Vivo 2021†
Fishchenko 2021†
Subtotal
At 12 months
Fischgrund 2018†
Smuck 2021 (BVN RFA Arm)
Macadaeg 2020
Becker 2017†
De Vivo 2021†
Fishchenko 2021†
Subtotal
Study
0.57 (0.48, 0.66)
0.67 (0.54, 0.79)
0.72 (0.59, 0.83)
0.96 (0.85, 0.99)
0.75 (0.48, 0.93)
0.73 (0.58, 0.84)
0.84 (0.60, 0.97)
0.75 (0.63, 0.86)
0.58 (0.49, 0.67)
0.69 (0.56, 0.80)
0.89 (0.76, 0.96)
0.63 (0.35, 0.85)
0.82 (0.69, 0.92)
0.84 (0.60, 0.97)
0.75 (0.63, 0.85)
ES (95% CI)
0.25 .5 .75 1
Pro
p
ortion
Proportions of patients reporting ≥15 point ODI improvement at six and 12 months
Figure 3. Proportions of patients reporting 15-point ODI improvement at 6 and 12months. †Exact threshold unpublished, data
requested and obtained from the study investigators.
0.40 0.50 0.60 0.70 0.80 0.90 1.00
Proportion
6 12 24 60
Months
N=376 N=317 N=162 N=100
Proportion of patients reporting ≥50% NRS/VAS improvement over time
Figure 4. Proportion of patients reporting 50% NRS/VAS improvement over time.
S58 Conger et al.
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of treatment with BVN RFA. Single-arm meta-analysis of
these studies demonstrated that approximately 65% and
75% of patients report clinically significant pain and
functional improvement at 6 and 12 months after BVN
RFA (Figures 2 and 3). The calculated proportions of res-
ponders remained remarkably stable at 24 and
60 months, with less than 5% variance in the estimated
VAS/ODI responder proportions (see Figures 4 and 5).
According to GRADE, the evidence quality was deter-
mined to be “moderate.” The designation of “moderate
quality” suggests that future research will likely improve
our understanding of the effectiveness of BVN RFA for
vertebrogenic pain [37].
In addition to safety, careful transpedicular access is
required to achieve targeting success with BVN RFA.
In studies that analyzed post-ablation lesion geometry
on MRI, targeting success appeared slightly higher
when the BVN was targeted at a point 30–50% from
the posterior wall [3,8,11] compared with earlier tar-
geting in SMART (40–60% from the posterior wall)
[7], though the targeting success rate remained above
90% in all studies (Table 1). DeVivo et al. reported
100% targeting success with the use of CT guidance
and an alternative device to that used in other studies
[1]. Given that studies after SMART have reported tar-
geting success rates greater than 95%, it appears that
successful neurotomy of the BVN is achieved fre-
quently with established techniques.
Because the BVN contains many unmyelinated fibers
[14,15,38,39], appropriately targeted thermal ablation
can produce a long-lasting neurotomy and durable symp-
tom improvement in those with significant pain and dis-
ability due to vertebrogenic LBP. This appears to be
supported by the existing literature, in which the vast
majority of study participants observed to initially bene-
fit from BVN RFA continued to report significant pain
and functional improvement at 1, 2, and 5 years
(Figures 2–5). This pattern appears to be the same in
industry-funded [3,7–10,36] and independently per-
formed studies [1,5]. Along with robust improvements
in pain and function, healthcare utilization appears to de-
crease substantially after BVN RFA. In published studies,
individuals treated with BVN RFA have seldom required
further interventional or surgical treatment. Of the par-
ticipants who were followed in the SMART trial, only
3% had received a lumbosacral facet joint RFA treatment
or spinal injection in the year preceding the 5-year data
collection time point [9]. Similarly, 5% of participants
from INTRACEPT received an epidural steroid injection
at a treated level by the 2-year data collection time point
[36]. In both of these studies, a minority of participants
progressed to a fusion surgery (8% and 4.5%, respec-
tively). Opioid utilization decreased in participants over
time after BVN RFA in most studies but did not differ
significantly from the sham or standard-of-care groups at
3–12 months [4,8,10]. Despite the lack of significant dif-
ference between control arms in the RCTs at 3 months,
the 5-year observational data from SMART (which in-
cluded crossover of sham patients to active treatment)
suggested that only 8% of participants were taking
opioids at long-term follow-up (compared with 30% at
baseline) [9].
No delayed complications were noted in any study re-
port. The most common reported adverse event remains
transient leg pain, which is thought to be secondary to
pedicle breach (see Table 1). Investigators reported an
11% rate (n ¼14) of pedicle breach resulting in “non-
serious” leg pain in the 127 participants treated with
0.40 0.50 0.60 0.70 0.80 0.90 1.00
Proportion
6 12 24 60
Months
N=377 N=317 N=163 N=100
Proportion of patients reporting ≥15 point ODI improvement over time
Figure 5. Proportion of patients reporting 15-point ODI improvement over time.
Basivertebral Nerve Ablation Systematic Review S59
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BVN RFA from the INTRACEPT study [36]. The median
time to resolution for these symptoms was 48.5 days, and
most were successfully treated with a single course of
oral steroids. Similar transient leg symptoms were ob-
served in the SMART population [7]. Two cases of retro-
peritoneal hemorrhage have been reported, which may
be due to excessive lateral positioning resulting in viola-
tion of the lumbar segmental artery [5,7].
Over the years, many interventional treatments have
been used for those with chronic “discogenic” LBP, with
varying success. Notable examples have included biacu-
loplasty, intradiscal RFA, methylene blue, and intradiscal
steroid injection [40–45]. More recently, case series of
patients treated with extraosseous, epiduroscopic BVN/
sinuvertebral nerve (SVN) laser ablation and bipolar
RFA have reported positive results [46–48].
Orthobiological treatments are also being adapted to
treat vertebrogenic LBP; a technique for intraosseous de-
livery of plasma-rich growth factor (PRGF-Endoret) has
been proposed [49]. Additionally, two recent RCTs in-
vestigating the effectiveness of intradiscal steroid in
patients with MC1 have been published, but they found
only short-term benefit at 1 month compared with intra-
discal saline or anesthetic [41,42]. Although there are no
head-to-head trials comparing BVN RFA with any of
these interventions in an appropriate population, there
are now multiple studies and 5-year outcomes to support
the use of BVN RFA for the treatment of vertebrogenic
pain. This is not the case for any of these other
treatments.
Although the outcomes of BVN RFA reported in the
published literature are robust, there could be opportuni-
ties to further refine patient selection. Until recently, the
characteristic pain patterns for those with vertebrogenic
LBP were not directly described; however, analysis of re-
sponder characteristics from a large population of
patients treated with BVN RFA has been reported [50].
Those with vertebrogenic pain experience predominantly
midline LBP without lower leg symptoms, but they also
indicated pain in the paramidline and buttock region.
Notably, these descriptions are based on a case definition
of significant pain relief or functional improvement after
BVN RFA (for lack of a superior gold standard of “true”
vertebrogenic pain). This is perhaps not surprising given
the substantial overlap in the known pain referral pat-
terns from other spinal structures, including the disc, sa-
croiliac joint, and zygapophyseal facet joint [51–53].
Given the widespread use of diagnostic/prognostic
blocks in interventional pain medicine, clinicians might
hope for a similar tool to help select patients for BVN
RFA. However, although directly anesthetizing the intra-
osseous BVN seems attractive as a diagnostic test at face
value, there are several major issues with this approach.
Anesthetic placed at the periosteum of the pedicle before
access would almost certainly anesthetize the lumbar me-
dial branch, potentially introducing confounding from
relief of lumbar zygapophyseal joint pain. Because of the
vascular nature of trabecular bone, local anesthetic injec-
tion within the vertebral body might not produce a con-
sistent blockade of the BVN, leading to false-negative
tests. Significant procedural pain after transpedicular ac-
cess might also be a source of false-negative results.
Given these challenges, clinicians are encouraged to care-
fully select patients for BVN RFA on the basis of the clin-
ical and imaging paradigm described in studies published
to date.
There are important limitations to this review and for
the existing literature related to BVN RFA. RCTs, al-
though not without their own limitations [54,55], con-
tinue to represent the gold-standard study design in
medical research [56]. Despite the growing interest in the
treatment of vertebrogenic LBP, the present updated re-
view found no new RCTs examining BVN RFA com-
pared with sham or any other treatment. The majority of
studies that met the inclusion criteria were supported by
industry funding. When the evidence for treatment comes
entirely from industry-funded studies, there is an in-
creased risk for bias given the inherent conflict of inter-
est, limiting the publication of negative results [57,58].
However, it is notable that results from two indepen-
dently performed studies show similarly high proportions
of patients reporting clinically significant pain relief and
functional improvement up to 12 months after BVN RFA
[1,5]. The present review was supported by an
investigator-initiated research grant from Relievant
Medsystems, which produces a device frequently used for
BVN RFA. However, the sponsor had no role in the de-
sign or conduct of the review or approval of the final
manuscript. The protocol, search, data extraction, and
statistical analysis were all developed and performed in-
dependently without input or oversight from the sponsor.
This review has several strengths. The review was
designed, executed, and reported in accordance with qual-
ity guidelines for systematic reviews [27,59]. Although
already performed in our prior work, abstract review, full-
text review, and data extraction were again performed in
duplicate to ensure accuracy. When data considered critical
to the review’s research question were missing, the authors
of included studies were contacted to obtain this informa-
tion. The single-arm meta-analysis presented provides clini-
cians with a useful estimate of the effectiveness of BVN
RFA when patients are selected on the basis of the pub-
lished inclusion and exclusion criteria used to date.
Conclusion
According to GRADE, there continues to be
“moderate”-quality evidence that BVN RFA effectively
reduces chronic LBP and associated disability in individu-
als with chronic vertebrogenic LBP associated with MC1
and MC2 in the L3 to S1 vertebral bodies. Between 65%
and 75% of such patients report clinically significant
pain and functional improvement at 6 and 12 months af-
ter BVN RFA, with similar success rates up to 5 years.
S60 Conger et al.
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Further high-quality studies will likely improve our un-
derstanding of the effectiveness of this procedure.
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