This document discusses the use of bone morphogenetic protein (BMP) in spinal fusions. It provides background on BMP and details several complications that have been reported with its use, including soft tissue swelling, ectopic bone formation, osteolysis, and inadvertent fusions. It also references studies that found higher than reported complication rates associated with BMP and suggests the minimally effective dose has not been determined. Case studies are presented of patients who experienced issues like psoas calcification, seromas, and retrograde ejaculation following procedures using BMP.

1. BMP
BMP in spinal fusions
December 22, 2020
Spine Conference

2. 7/7/17
84 year old woman LBP B
Sciatica
HPI: years of pain, non-
operative due to
Age ad complexity of surgery
PMH: htn, L nephrectomy
1996,
SH: lives alone assisted living
5’5” 112 lb

3. 12/20/16

4. T12L1 L1L2 L2L3
L3L4 L4L5 L5S1
12/10/16

5. 7/11/17

6. 3
L3L4 L4L5
L1L2 L2L3
7/11/17
Why are roots clumped together and on the right side of canal?

7. Problem list:
1. Mid Octogenarian alert
and healthy but frail
2. Severe stenosis L2L3
3. Severe stenosis L3L4
4. L3L4 listhesis
5. Apex curve at L2L3
6. Unable to walk
7. L L1L4 scoliosis

10. 9/18/17

11. 11/30/17

12. 10/20/20
3 years later no pain
Walks 30 min/day
Recently referred a friend

14. Bone Graft
 Iliac crest
 Local
 Allograft: structural, morselized
 BMP
 DBM
 Ceramic: tricalcium phosphate and corraline
hydroxyapatitie

15. ILIAC CREST

17. CANCELLOUS ALLOGRAFT

18. Marshall Urist
made the key
discovery that
demineralized,
lyophilized segments
of bone induced new
bone formation
when implanted in
muscle pouches in
rabbits
^ Urist, Marshall R. (1965). "Bone: formation by
autoinduction". Science 12:150 (698): 893–
899. doi:10.1126/science.150.3698.893. PMID 5319761

19. INFUSE rhBMP-2
impregnated absorbable collagen sponges
• FDA approval 7/2/02 for the
treatment of L4S1 ALIF for
DDD after 6 month of nonop
treatment can include grade 1
spondylolisthesis.Lumbar
tapered Fusion device.
• FDA approval 12-4-15 for
interbody devices PEEK lumbar
up to grade 1 sponylolisthesis
(Clydesdale Oblique Lateral IF)
• Stryker Biotch OP-1/rhBMP-7
in 2003

20. INFUSE rh_BMP-2
• FDA approved
4/30/04 for
acute open
tibial fractures
treated with IM
nailing within 14
days of injury
J Bone Joint Surg Am. 2002 Dec;84-A(12):2123-34.
Recombinant human bone morphogenetic protein-2 for
treatment of open tibial fractures: a prospective,
controlled, randomized study of four hundred and fifty
patients

21. BMP complications list
• Delayed wound healing
• Infection
• Hematoma
• Seroma
• Radiculitis
• Neck swelling
• Heterotopic calcification
• Retrograde ejaculation
• Antibody formation
• Vertebral osteolysis
• Epidural hematoma/seroma
• New onset of cancer

22. By 2007, more than 50% of primary ALIF, 43%
of
PLIF/transforaminal lumbar interbody fusion
(TLIF), and
30% of PLF were reported to use rhBMP-2 [
Spinal sales were $3.5B in 2010 with a 50%
US market share, sales of infuse were $700M
2020: $2.5B spine revenues currently $152B
market cap company, Ireland, Infuse sales not
broken out in annual report or quarter
conference all

24. COST: $5k case

25. Soft Tissue swelling s/p acdf with fibular allograft

26. Adverse swelling associated with use of rh-BMP-2
in anterior cervical discectomy and fusion: a case study
Brian Perri, DO*, Martin Cooper, MD, Carl Lauryssen, MD, Neel Anand, MD
The Spine Journal 2007

27. ORTHOPEDIC AND DENTAL INDUSTRY
NEWS COMPLETE ARCHIVE »
FDA Issues Warning Regarding Off-Label
Use of rhBMPBY LAUREN UZDIENSKI,
JULY 7, 2008
Last week the FDA released a public
health notification regarding the off-
label use of of rhBMP (InFuse, OP-1)
in the cervical spine. The agency says
that over the past four years there
have been at least 38 reports of
complications associated with using
BMP in unapproved cervical fusion
cases, ranging from difficulty
swallowing, breathing or speaking to
severe dysphagia.
Most reported complications occurred
between two and 14 days following
surgery. Treatments included
respiratory support with intubation,
anti-inflammatory medication,
tracheotomy and most commonly
second surgeries to drain the surgical
site. The seriousness of the
complications was correlated with the
anatomical proximity of the cervical
spine to airway structures. The FDA
adds, "The mechanism of action is
unknown, and characteristics of
patients at increased risk have not
been identified."

30. Dr. Ed Carragee Stanford
A critical review of BMP FDA trial literature
versus data obtained after it is on the
market
Carragee, EL Hurwitz… - The Spine Journal,
2011
Overreported complication rates for ICBG
Underreported complication rates for BMP
(10-50 times)
40% ACDF
Ectopic bone formation, subsidence of
grafts, radiculitis, osteolysis, seroma,
infections, inadvertent fusions, RE

32. 45 woman infection one year out

33. Adjacent level
inadvertent
fusion of facet

35. Retrograde ejaculation ALIF
• The underlying mechanism of the dysfunction is the
inability of the internal vesical sphincter to contract
during ejaculation, resulting in retrograde flow of
semen to the urinary bladder.[13] As the muscle is
innervated by the superior hypogastric plexus, i.e., a
thin, retroperitoneal plexus of nerves overlying the
lumbosacral junction, damage to the plexus during (or
after) ALIF can denervate the bladder neck
sphincterRetrograde Ejaculation after ALIF with rh-BMP
• 7% versus 0.5%
• Retrograde ejaculation after anterior lumbar interbody
fusion using rhBMP-2: a cohort controlled study
• Eugene J. Carragee, MD The Spine Journal 2011

36. POSTOPERATIVE SEROMA
• Postoperative Cervical Myelopathy and Cord
Compression Associated with the Use of rh-
BMP-2 in Posterior Cervical Decompression,
Instrumentation, and Arthrodesis: A report of
two cases; Anderson DW, Burton DC, Jackson RS;
Spine (Jan 2011)

37. 774 man with postoperative
seroma POD #8 I&D bedside

38. 66 YEAR OLD
WOMAN S/P L4L5
PSF ADMITTED FOR
LBP POD #18

40. 26 studies pooled on 184k patients; U of basel, Harvard
78% increased complication rate; HO in the neural foramen

41. Psoas calcification
• Brower RS, Vickrov NM. A case of psoas ossification from the use of BMP-2 for
posterolateral fusion at L4-L5. Spine 2008;33:E653-55.
• Rob D Dickerman, Ashley S Reynolds, Matthew Bennett in Spine (2009)

42. 77 year old woman with cc: LBP B buttock pain PMH: type 2 DM, HTN,

43. L3L4

44. LEFT PSOAS

46. COMPLAINTS OF LEFT GROIN AND THIGH PAIN PROMPTED CT OF THE
ABDOMEN AND HIP POD #32 WHICH REVEALED CALCIFICATIONS AND
SWELLING OF THE LEFT PSOAS MUSCLE

47. MRI 9/24/09 which was 7 weeks postop revealed evolving calcification
of the psoas c/w myositis ossificans

48. Retrospective cohort study Washington State Data Bases, spinal fusions 2002-2010, matched control each surgery with 3 patients
age/sex/year through the end of 2015
16,914 patients with 4,246 receiving BMP; cancer rate was 11.2/1000 person years for BMP, 10.4 for control
Patients with a dx of cancer were excluded,
BMP invitro has been shown to promote tumor growth, therefore it is contraindicated to apply in the vicinity of tumor, for patients with
any known active malignancy, or thorse receiving treatment for a malignancy;

49. Dosage and placement, determine MED minimally effective dose, metaanalysis,
complications of osteolysis, HO, radiculitis, ca; locations: interbody cage, posterolateral
gutter PLG, cage and interspace, interspace and PLG;
Doses were 1.28-12 mg/level;mild increase in osteolysis with cage; fusion rates did not
differ;
Unable to find MED

50. 60 WOMAN CC: L SCIATICA S/P L3L5 POSTERIOR DECOMPRESSION WITH L4L5
INSTRUMENT FUSION ON 9/29/08 INTIALLY DID WELL BUT HAD RECURRENT SCIATICA
IN MARCH 2011. REPEAT MRI SCAN REVEILED A L L5S1 LATERAL RECESS COMPRESSIVE
PROCESS FROM THE L L5S1 FACET/DISC SPACE,BUT ALSO OVERGROWTH OF THE L4L5
FACET FUSION PROCESS WHERE BMP WAS PLACED

52. THANKS!