Journal of Orthopaedic Surgery 2016;24(2):222-7
Bioceramic bone graft substitute for treatment
of unicameral bone cysts
Yale A Fillingham, Gregory L Cvetanovich, Bryan D Haughom, Brandon J Erickson, Steven Gitelis
Rush University Medical Center, United States
ABSTRACT
Purpose. To review the outcome of 12 patients who
underwent debridement and injection of bioceramic
for unicameral bone cyst (UBC). The resorption rate
of the bioceramic was estimated by both traditional
and novel methods.
Methods. Records of 10 males and 2 females aged 6 to
34 years who underwent debridement and injection
of bioceramic for UBC and were followed up for a
mean of 41 (range, 26–57) months were reviewed.
Functional outcome was assessed using the selfcompleted Musculoskeletal Tumor Society (MSTS)
questionnaire. Radiological outcome was assessed
using both original and modified Neer Outcome
Rating System. The resorption rate of the bioceramic
was estimated using both traditional and novel
(ImageJ) methods.
Results. The mean MSTS score was 29.7 (range,
28–30) indicating excellent functional outcome. Of
the 12 patients, 9 achieved complete healing and
3 had a residual cyst of 1%, 11%, and 52%. The last
was considered a local recurrence, and the patient
underwent repeat percutaneous injection of the
bioceramic 1.5 years later and remained disease-free
4 years later. The mean resorption rate was 29% faster
when estimated using the traditional rather than the
ImageJ method (0.47 vs. 0.33 cm3/day, p=0.02). In the
patient with recurrence, the resorption rate was faster
than the average (0.68 vs. 0.33 cm3/day).
Conclusion. A single percutaneous injection of the
bioceramic for UBC achieved good functional and
radiological outcome while avoiding donor-site
morbidity.
Key words: bone cysts; calcium phosphate; calcium
sulfate
INTRODUCTION
Unicameral bone cyst (UBC) is a benign tumour,
accounting for approximately 3% of all biopsied
bone tumours.1 Its treatment has evolved from
diaphysectomy to open/percutaneous curettage and
bone grafting.2 Nonetheless, there is no consensus on
Address correspondence and reprint requests to: Yale A Fillingham, Rush University Medical Center, United States. Email:
[email protected]
Vol. 24 No. 2, August 2016
Bioceramic bone graft substitute for treatment of unicameral bone cysts 223
the use of corticosteroids, allografts, autografts, bone
substitutes, or their combination. The recurrence rate
of UBC has been reported to be 11% to 77%.3–11 In
56 patients who underwent curettage and injection
of bioceramic for benign bone tumours, the mean
Musculoskeletal Tumor Society (MSTS) functional
score was 29 after a mean follow-up of 42 months.12
Autogenous bone grafts are widely used and
remain the gold standard for grafting.12 Owing to
its limited supply and donor-site morbidity, the
use of bone substitutes is increasingly popular.13,14
Calcium sulfate (CaSO4) and calcium phosphate
(CaPO4) are osteoconductive and biodegradable,15,16
and have been used to treat benign bone lesions.15,17
An injectable composite of CaSO4 and CaPO4
takes advantage of their different resorption and
mechanical profiles to improve the compressive
strength and intermediate resorption profile when
compared with CaSO4 pellets.12,16 The bioceramic is
composed of a matrix of surgical grade 75% CaSO4
and 25% dicalcium phosphate dihydrate (DCPD)
and β-tricalcium phosphate (β-TCP) granules, which
provide a triphasic resorption profile and good
biocompatibility.16 Under simple dissolution, the
CaSO4 resorbs thereby creating a porous scaffold
of CaPO4 that provides a surface for early vascular
infiltration and deposition of osteoblasts and
osteoclasts. The resulting scaffold surface of DCPD
and β-TCP forms interconnecting pores, which is
capable of binding growth factors such as vascular
endothelial growth factor and bone morphogenic
proteins to help recruit osteoblasts. The remaining
CaPO4 undergoes osteoclastic resorption with the
DCPD creating an intermediate profile and β-TCP
as the final phase of resorption. Based on a canine
model with a humeral osseous defect, the composite
(a)
(b)
(c)
of CaSO4 and CaPO4 was clinically superior to CaSO4
and had equivalent properties to normal bone.16
This study reviewed the outcome of 12 patients
who underwent debridement and injection of
bioceramic for UBC (Fig. 1). The resorption rate of
the bioceramic was estimated by both traditional and
novel methods.
MATERIALS AND METHODS
This study was approved by the institutional review
board of our hospital. Records of a consecutive series
of 19 patients with a UBC treated with debridement
and injection of a bioceramic—Pro-Dense (Wright
Medical Technology, Arlington [TN], USA)—from
2006 to 2009 by a single surgeon were retrospectively
reviewed. Of them, 5 had inadequate radiographs,
one was lost to follow-up, and one had hardware
obstructing the view of the entire graft. The remaining
10 males and 2 females aged 6 to 34 years were
followed up for a mean of 41 (range, 26–57) months.
A period of 12 months is adequate to evaluate
recurrence or fracture of a UBC after treatment.4,14,18,19
A percutaneous 2-needle technique was used. A
small incision was made, followed by blunt dissection
of the overlying cortex. A small cortical window was
opened using a high-speed bur to allow aspiration
of the cyst fluid and curettage of the fibrous lining
for biopsy. The diagnosis was confirmed by frozen
section. A second cortical window was opened
under fluoroscopic guidance. The UBC was debrided
through two 4-mm cannulas and then copiously
lavaged with the second cortical window as an
outlet. The bioceramic was prepared by mixing the
powdered graft materials with aqueous diluents. It
(d)
Figure 1 Serial radiographs showing graft resorption and subsequent bone repair after percutaneous injection of Pro-Dense
for a UBC of the proximal humerus: (a) before treatment and (b) one week, (c) 10 months, and (d) 5 years after treatment.
Journal of Orthopaedic Surgery
224 YA Fillingham et al.
Table 1
Modified Neer Outcome Rating System
Rating
Area of cyst
Cortical thickness
Clinical outcome
Healed
Partially healed
Persistent
Recurrence
Complete obliteration
<50% remains
>50% remains
No change or enlargement
Increased
Increased
Unchanged or thinned (<0.3 mm)
Thinned (<0.3 mm)
Success
Success
Failure
Failure
was injected into the cavity under fluoroscopy, with
the second cortical window as a vent.
Postoperatively, patients with a lower-limb lesion
were instructed to have protected weight-bearing
using crutches for 8 weeks, and those with an upperlimb lesion were instructed to avoid lifting objects for
8 weeks. Patients were followed up weekly and then
at 1, 6, 12, and 18 months.
Functional outcome was assessed using the
self-completed MSTS questionnaire.20 For lower
limbs, items include emotional acceptance, walking
supports (including brace, prosthesis, cane, or
crutches), walking ability, and gait. For upper limbs,
items include function, emotional acceptance, hand
positioning, dexterity, and lifting ability. Score for
each item ranges from 0 to 5; the maximum total score
is 30.
Radiological outcome was assessed at the
final follow-up by 2 independent assessors using
both original and modified Neer Outcome Rating
System.4,18,21,22 For the former, outcome was considered
‘excellent’ when the UBC was completely obliterated,
as ‘residual defect’ when there was single or multiple
persistent cystic residua but with good bone
strength, as ‘reoperation’ when the UBC recurred
necessitating further operative intervention. For the
latter, ‘persistent’ and ‘recurrence’ were considered
a failure, whereas ‘partially healed’ and ‘healed’ was
considered a success so long as there was good bone
strength (Table 1).
The resorption rate of the bioceramic was
estimated using both traditional and novel (ImageJ)
methods (Fig. 2). For the former, the graft volume was
estimated based on the dimension (length and width)
of a rectangular prism on 2 orthogonal radiographs,23
but this does not account for irregular shapes. For the
latter, the graft volume was estimated based on the
length, width, and irregular shapes calibrated with a
known distance marker on 2 orthogonal radiographs
using the ImageJ.24 The resorption rates estimated
by the 2 methods were compared using the paired
t-test. A p value of <0.05 was considered statistically
significant.
(a)
(b)
Figure 2 Radiographs of the humerus at (a) week 1 and (b)
week 6 showing the traditional method to measure the length
and width of the graft volume (white lines) and the novel
(ImageJ) method to include irregular shapes (yellow outline)
for estimation of graft resorption.
RESULTS
The mean MSTS functional score was 29.7 (range, 28–
30) for all patients, 29.3 for those with a lower-limb
lesion, and 29.8 for those with an upper-limb lesion
(Table 2). According to the Neer Outcome Rating
System, the outcome was excellent in 9, residual defect
in 2, and reoperation in one patient. According to the
Modified Neer Outcome Rating System, the outcome
was healed in 9, partially healed in 2, persistent in
one, and recurrence in none. For the 3 patients with a
residual cyst, the volume was 1%, 11%, and 52%. The
last was a 9-year-old boy with a UBC in the proximal
humerus who had a local recurrence 1.5 years later
(Fig. 3). He underwent repeat percutaneous injection
of the bioceramic and remained disease-free 4 years
later. No patient had postoperative fractures or
wound complications.
The mean resorption rate was 29% faster when
estimated using the traditional rather than ImageJ
Vol. 24 No. 2, August 2016
Bioceramic bone graft substitute for treatment of unicameral bone cysts 225
Table 2
Patient characteristics and outcome
Sex/age
(years)
M/7
M/16
M/9
M/12
F/34
M/6
M/18
M/11
M/13
M/15
F/13
M/12
(a)
Tumour
site
Humerus
Humerus
Humerus
Humerus
Humerus
Metatarsal
Tibia
Humerus
Femur
Humerus
Humerus
Humerus
Follow- Musculoskeletal Neer Outcome Modified Neer Resorption (cm3/day)
up
Tumor Society Rating System
Outcome
Traditional
ImageJ
(months)
score
Rating System
method
method
51.2
41.0
53.7
52.0
36.0
45.3
54.8
47.6
57.3
31.5
26.1
32.6
28
30
30
30
30
30
30
30
28
30
30
30
Residual defect Partially healed
Excellent
Healed
Reoperation
Persistent
Excellent
Healed
Excellent
Healed
Excellent
Healed
Excellent
Healed
Excellent
Healed
Excellent
Healed
Excellent
Healed
Residual defect Partially healed
Excellent
Healed
0.472
0.629
0.720
0.493
1.207
0.028
0.412
0.461
0.287
0.217
0.491
0.193
0.395
0.527
0.679
0.441
0.578
0.017
0.280
0.330
0.193
0.064
0.357
0.158
Comments
11% residual cyst
52% residual cyst
1% residual cyst
-
method (0.47 [range, 0.03–1.21] vs. 0.33 [range, 0.02–
0.68] cm3/day, p=0.02). In the patient with recurrence,
the resorption rate was faster than the average (0.68
vs. 0.33 cm3/day).
(b)
DISCUSSION
Figure 3 Based on the ImageJ method, (a) preoperative
and (b) 1.5-year postoperative radiographs of the proximal
humerus showing the size of the unicameral bone cyst as 132
cm3 and resolution of the proximal portion but persistence of
the distal portion (69 cm3).
(a)
(b)
Figure 4 (a) Radiography and (b) computed tomography
showing complete graft resorption and bone repair of a
healed cyst at 10 months.
For treatment of simple bone cysts, percutaneous
injection of bone marrow or methylprednisone
achieves comparable Activity Scale for Kids score
and Oucher pain score.11 The recurrence rate has
been reported to be 11% to 77% after a single
injection of materials (corticosteroids, allograft
bone, autograft bone, bone graft substitutes, or a
combination of these).3–11,25 The success rate has
been reported to be 77% after autogenous grafting
and 69% after homogenous grafting.22 One study
reported an overall success rate of 86.7% and 92.0%
following percutaneous injection of steroid and
autogenous bone marrow, respectively, but the mean
number of procedures performed was 2.19 and 1.57,
respectively.5 One study reported a success rate of
84.6% after a single percutaneous injection of apatitic
calcium phosphate.18 Compared with calcium sulfate
pellets, Pro-Dense results in a higher percentage of
bone formation, greater ultimate compressive stress,
and an elastic modulus that more closely resembles
normal bone.16 Curettage and grafting with calcium
sulfate pellets results in a recurrence rate of 17% to
26% and a complication rate of 0% to 8%.26–28 In our
series, the recurrence rate was 8% and the success
rate was 92% after a single percutaneous injection of
bioceramic.
Graft resorption can be measured based on the
Journal of Orthopaedic Surgery
226 YA Fillingham et al.
percentage of opacification29 or the length and width
of a rectangular prism on 2 radiographs,17,23,30 but
these methods do not accurately account for irregular
shapes. This can be overcome with use of the ImageJ
that is calibrated using a known distance marker. In
our series, the traditional method overestimated the
resorption rate by 29%. The accuracy of the Image J
method could have been validated by comparing the
intra-operative amount of bioceramic injected with
the estimated volume on an immediate postoperative
radiograph, but this would have exposed the patient
to unnecessary radiation.
This study had limitations. The study was
retrospective in nature, and the sample size was
small, but given the rarity of UBC the sample size
was consistent with other studies. Graft resorption
was not measured histologically to correlate with
radiographic findings. Nonetheless, a bone biopsy is
impractical. In one patient evaluated with computed
tomography prior to returning to high-level
contact sports, the results correlated with those by
radiography (Fig. 4).
CONCLUSION
A single percutaneous injection of the bioceramic
for UBC achieved good functional and radiological
outcome while avoiding donor-site morbidity.
DISCLOSURE
No conflicts of interest were declared by the authors.
REFERENCES
1. Wilkins RM. Unicameral bone cysts. J Am Acad Orthop Surg 2000;8:217–24.
2. McKay DW, Nason SS. Treatment of unicameral bone cysts by subtotal resection without grafts. J Bone Joint Surg Am
1977;59:515–9.
3. Capanna R, Dal Monte A, Gitelis S, Campanacci M. The natural history of unicameral bone cyst after steroid injection. Clin
Orthop Relat Res 1982;166:204–11.
4. Chang CH, Stanton RP, Glutting J. Unicameral bone cysts treated by injection of bone marrow or methylprednisolone. J
Bone Joint Surg Br 2002;84:407–12.
5. Cho HS, Oh JH, Kim HS, Kang HG, Lee SH. Unicameral bone cysts: a comparison of injection of steroid and grafting with
autologous bone marrow. J Bone Joint Surg Br 2007;89:222–6.
6. Docquier PL, Delloye C. Treatment of aneurysmal bone cysts by introduction of demineralized bone and autogenous bone
marrow. J Bone Joint Surg Am 2005;87:2253–8.
7. Kanellopoulos AD, Yiannakopoulos CK, Soucacos PN. Percutaneous reaming of simple bone cysts in children followed by
injection of demineralized bone matrix and autologous bone marrow. J Pediatr Orthop 2005;25:671–5.
8. Killian JT, Wilkinson L, White S, Brassard M. Treatment of unicameral bone cyst with demineralized bone matrix. J Pediatr
Orthop 1998;18:621–4.
9. Rougraff BT, Kling TJ. Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix
and autogenous bone marrow. J Bone Joint Surg Am 2002;84:921–9.
10. Sung AD, Anderson ME, Zurakowski D, Hornicek FJ, Gebhardt MC. Unicameral bone cyst: a retrospective study of three
surgical treatments. Clin Orthop Relat Res 2008;466:2519–26.
11. Wright JG, Yandow S, Donaldson S, Marley L; Simple Bone Cyst Trial Group. A randomized clinical trial comparing
intralesional bone marrow and steroid injections for simple bone cysts. J Bone Joint Surg Am 2008;90:722–30.
12. Fillingham YA, Lenart BA, Gitelis S. Function after injection of benign bone lesions with a bioceramic. Clin Orthop Relat
Res 2012;470:2014–20.
13. Goulet JA, Senunas LE, DeSilva GL, Greenfield ML. Autogenous iliac crest bone graft. Complications and functional
assessment. Clin Orthop Relat Res 1997;339:76–81.
14. Hashemi-Nejad A, Cole WG. Incomplete healing of simple bone cysts after steroid injections. J Bone Joint Surg Br
1997;79:727–30.
15. Matsumine A, Kusuzaki K, Matsubara T, Okamura A, Okuyama N, Miyazaki S, et al. Calcium phosphate cement in
musculoskeletal tumor surgery. J Surg Oncol 2006;93:212–20.
16. Urban RM, Turner TM, Hall DJ, Inoue N, Gitelis S. Increased bone formation using calcium sulfate-calcium phosphate
composite graft. Clin Orthop Relat Res 2007;459:110–7.
17. Kelly CM, Wilkins RM, Gitelis S, Hartjen C, Watson JT, Kim PT. The use of a surgical grade calcium sulfate as a bone graft
substitute: results of a multicenter trial. Clin Orthop Relat Res 2001;382:42–50.
18. Thawrani D, Thai CC, Welch RD, Copley L, Johnston CE. Successful treatment of unicameral bone cyst by single percutaneous
injection of alpha-BSM. J Pediatr Orthop 2009;29:511–7.
19. Lokiec F, Ezra E, Khermosh O, Wientroub S. Simple bone cysts treated by percutaneous autologous marrow grafting. A
preliminary report. J Bone Joint Surg Br 1996;78:934–7.
20. Enneking WF, Dunham W, Gebhardt MC, Malawar M, Pritchard DJ. A system for the functional evaluation of reconstructive
Vol. 24 No. 2, August 2016
Bioceramic bone graft substitute for treatment of unicameral bone cysts 227
procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop Relat Res 1993;286:241–6.
21. Neer CS, Francis KC, Johnston AD, Kiernan HA Jr. Current concepts on the treatment of solitary unicameral bone cyst. Clin
Orthop Relat Res 1973;97:40–51.
22. Neer CS 2nd, Francis KC, Marcove RC, Terz J, Carbonara PN. Treatment of unicameral bone cyst. A follow-up study of one
hundred seventy-five cases. J Bone Joint Surg Am 1966;48:731–45.
23. Hirata M, Murata H, Takeshita H, Sakabe T, Tsuji Y, Kubo T. Use of purified beta-tricalcium phosphate for filling defects after
curettage of benign bone tumours. Int Orthop 2006;30:510–3.
24. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012;9:671–5.
25. Kose N, Gokturk E, Turgut A, Gunal I, Seber S. Percutaneous autologous bone marrow grafting for simple bone cysts. Bull
Hosp Jt Dis 1999;58:105–10.
26. Hou HY, Wu K, Wang CT, Chang SM, Lin WH, Yang RS. Treatment of unicameral bone cyst: a comparative study of selected
techniques. J Bone Joint Surg Am 2010;92:855–62.
27. Mik G, Arkader A, Manteghi A, Dormans JP. Results of a minimally invasive technique for treatment of unicameral bone
cysts. Clin Orthop Relat Res 2009;467:2949–54.
28. Peltier LF, Jones RH. Treatment of unicameral bone cysts by curettage and packing with plaster-of-Paris pellets. J Bone Joint
Surg Am 1978;60:820–2.
29. Dormans JP, Sankar WN, Moroz L, Erol B. Percutaneous intramedullary decompression, curettage, and grafting with
medical-grade calcium sulfate pellets for unicameral bone cysts in children: a new minimally invasive technique. J Pediatr
Orthop 2005;25:804–11.
30. Anker CJ, Holdridge SP, Baird B, Cohen H, Damron TA. Ultraporous beta-tricalcium phosphate is well incorporated in
small cavitary defects. Clin Orthop Relat Res 2005;434:251–7.