I read with interest the recent paper by Steinhausen et al. (2021).
This paper reports the outcome of a retrospective review of bioactive glass
compared to autologous bone graft (ABG) in a staged surgical protocol for
treating established bone infection. The authors claim that bioglass is
equally effective as ABG in eradicating infection but acknowledge that their
evidence is weak.
The surgical treatment of chronic bone infection has been reported for well
over a century. In 1931, Jacob Kulowski published his classical series of 130
cases of osteomyelitis, treated by Orr's method (Kulowski, 1931). His
surgical debridement technique was similar to that described by Steinhausen
et al. (2021), and he achieved a recurrence rate of 24 % (mean follow-up:
19 months), in the pre-antibiotic era, with no defect fillers. In this new
series of 83 patients, the recurrence rate with bioglass was 29 % and
19 % for ABG. Clearly the addition of bioglass or bone graft has not
improved outcome.
The authors state that the longer follow-up period for the ABG group is not
a source of bias because “most complications occurred within 12 months”.
This same group previously published 50 of their 51 bioglass cases (Malat et
al., 2018) with a mean follow-up of 12.3 months and a recurrence rate of
14 %. This has increased to 29 % with a longer follow-up (mean 20.5 months). It would appear that the recurrence rate doubled in the 8 months
after the first year.
There are no large randomized trials directly comparing the use of bioglass
with other options, and the authors correctly report that outcomes of small
studies are inconclusive. However, there are two high-quality animal studies
(Xie et al., 2009; Boot et al., 2020). In a rabbit model of MRSA
osteomyelitis, Xie et al. (2009) reported that bioglass was no more
effective than debridement alone (success rate 36 % for debridement and
18 % for debridement and bioglass) but the addition of local antibiotics
to calcium sulfate or bioglass increased success to 73 % and 81 %
respectively. Boot et al. (2020) studied the effect of hydrogel and bioglass
in an infected tibial nail model. They showed that bioglass or hydrogel
without antibiotics produced no reduction in infection, but
vancomycin-loaded hydrogel could eradicate established infection.
It has been widely claimed that bioglass has the advantage of reducing the
risk of antimicrobial resistance. This paper shows that cases treated with
bioglass required significant additional systemic antimicrobial therapy
after repeated surgery or recurrence. It has been shown that repeated
surgery promotes change in bacterial cultures (Rupp et al., 2020).
Recurrent, and often suboptimal, systemic therapy drives selection pressure
and multi-drug resistance. There is no evidence that local antimicrobial
therapy contributes to this. The recent study of Bidossi et al. (2020)
demonstrated that prolonged exposure to high-dose local antibiotics in a
ceramic carrier was not associated with any adaptations in bacteria
producing antimicrobial resistance. In contrast to bioglass, the use of
local antimicrobials may allow reduced systemic therapy and better
antibiotic stewardship (Masrouha et al., 2018; Dudareva et al., 2019).
Steinhausen et al. (2021) also claim that “The tolerability of BAG is even
described as superior when compared to other bone substitutes”. We cannot
find any evidence for this statement in their paper. When comparing to the
paper they quote as evidence (McNally et al., 2016), the claim is not
supported. If we compare recurrence rate, reoperation rate, failure of bone
healing and amputation rate between the two papers, they report 29 %,
47 %, 23 % and 6 % respectively. In our study of 100 cases, the
figures were 4 %, 3 %, 13 % and 0 %. We believe these outcomes would
be more tolerable for patients.
Perhaps the most important conclusion from this paper is that serial
debridement, followed by defect filling without local antimicrobials, is
not a very effective treatment. We would not recommend use of a hip or knee
prosthesis with a 29 % failure rate within 2 years. This problem was
identified in the 1970s and prompted the use of antibiotic-loaded PMMA
beads by Klemm and Buchholz (Klemm, 1993). There is now encouraging evidence
around the use of single-stage surgery, facilitated by modern local
antibiotic carriers, with few complications and high infection eradication
rates, even in the most complex cases (Masrouha et al., 2018; McNally et
al., 2016; Ferguson et al., 2014; Lam et al., 2019; Pincher et al., 2019;
Lorentzen et al., 2020; Drampalos et al., 2018; Jiang et al., 2020; Pesch et
al., 2020; Hutting et al., 2021; Mifsud et al., 2020; Zhou et al., 2021).
Code and data availability
All data pertaining to this letter is included in the text.
Competing interests
Martin McNally is an associate editor of this journal.
ReferencesBidossi, A., Bottagisio, M., Logoluso, N., and de Vecchi, E.: In vitro evaluation of
gentamicin or vancomycin containing bone graft substitute in the prevention
of orthopedic implant-related infections, Int. J. Mol. Sci., 21, 9250,
10.3390/ijms2139250, 2020.Boot, W., Vogely, H., Nikkels, P., Pouran, B., van Rijen, M., and Ekkelenkamp, M.:
Prophylaxis of implant-related infections by local release of vancomycin
from a hydrogel in rabbits, Eur. Cells Mater., 39, 108–120, 2020.Drampalos, E., Mohammad, H. R., Kosmidis, C., Balal, M., Wong, J., and Pillai, A.:
Single stage treatment of diabetic calcaneal osteomyelitis with an
absorbable gentamicin-loaded calcium sulphate/hydroxyapatite biocomposite:
The Silo technique, Foot, 34, 40–44, 2018.Dudareva, M., Kümin, M., Vach, W., Kaier, K., Ferguson, J., McNally, M.,
and Scarborough, M.: Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): A
randomised controlled open-label non-inferiority trial of duration of
systemic antibiotics in adults with orthopaedic infection treated
operatively with local antibiotic therapy, Trials, 20, 693, 10.1186/s13063-019-3832-3, 2019.Ferguson, J. Y., Dudareva, M., Riley, N. D., Stubbs, D., Atkins, B. L., and McNally, M. A.:
The use of a biodegradable antibiotic-loaded calcium sulphate carrier
containing tobramycin for the treatment of chronic osteomyelitis, Bone Joint
J., 96, 829–836, 2014.Hutting, K. H., aan de Stegge, W. B., van Netten, J. J., ten Cate, W. A., Smeets, L.,
Welten, G. M. J. M., Scharn, D. M., de Vries, J.-P. P. M., and van Baal, J. G.: Surgical
Treatment of Diabetic Foot Ulcers Complicated by Osteomyelitis with
Gentamicin-Loaded Calcium Sulphate-Hydroxyapatite Biocomposite, J. Clin.
Med., 10, 371, 10.3390/jcm10020371, 2021.Jiang, N., Zhao, X., Wang, L., Lin, Q., Hu, Y., and Yu, B.: Single-stage debridement
with implantation of antibiotic-loaded calcium sulphate in 34 cases of
localized calcaneal osteomyelitis, Acta Orthop., 91, 353–359, 2020.Klemm, K.: Antibiotic bead chains, Clin. Orthop. Relat. Res., 295, 63–76,
1993.Kulowski, J.: The Orr treatment of osteomyelitis and allied suppurative
processes, J. Bone Joint Surg. Am., 13, 538–562, 1931.Lam, A., Richardson, S. S., Buksbaum, J., Markowitz, J., Henry, M. W., Miller, A. O.,
Rozbruch, S. R., and Fragomen, A. T.: Chronic Osteomyelitis of the tibia and ankle
treated with Limb Salvage Reconstruction, J. Bone Joint Infect., 4,
306–313, 10.7150/jbji.40337, 2019.Lorentzen, A. K., Engel, L., Gottlieb, H., Obinah, M. P. B.: One-stage treatment of
chronic osteomyelitis with an antibiotic-loaded biocomposite and a local or
free flap, Eur. J. Plast. Surg., 44,
367–374, 10.1007/s00238-020-01754-5, 2020.Malat, T., Glombitza, M., Dahmen, J., Hax, P.-M., and Steinhausen, E.: The Use of
Bioactive Glass S53P4 as Bone Graft Substitute in the Treatment of Chronic
Osteomyelitis and Infected Non-Unions – a Retrospective Study of 50
Patients, Z. Orthop. Unfallchir., 156,
152–159, 2018.Masrouha, K. Z., Raad, M. E., and Saghieh, S. S.: A novel treatment approach to
infected nonunion of long bones without systemic antibiotics, Strategies in
Trauma and Limb Reconstruction, 13, 13–18, 2018.McNally, M. A., Ferguson, J. Y., Lau, A. C. K., Diefenbeck, M., Scarborough, M., Ramsden, A. J., and Atkins, B. L.: Single-stage treatment of chronic osteomyelitis
with a new absorbable, gentamicin-loaded, calcium sulphate/ hydroxyapatite
biocomposite: a prospective series of 100 cases, Bone Joint J., 98-B,
1289–1296, 2016.Mifsud, M., Ferguson, J. Y., Stubbs, D. A., Ramsden, A. J., and McNally, M. A.:
Simultaneous debridement, Ilizarov reconstruction and free muscle flaps in
the management of complex tibial infection, J. Bone Joint Infect., 6,
63–72, 10.5194/jbji-6-63-2020, 2020.Pesch, S., Hanschen, M., Greve, F., Zyskowski, M., Seidl, F., and Kirchhoff, C.:
Treatment of fracture-related infection of the lower extremity with
antibiotic-eluting ceramic bone substitutes: case series of 35 patients and
literature review, Infection, 48, 333–344, 2020.Pincher, B., Fenton, C., Jeyapalan, R., Barlow, G., and Sharma, H. K.: A systematic
review of the single-stage treatment of chronic osteomyelitis, J. Ortho.
Surg. Res., 14, 393, 10.1186/s13018-019-1388-2, 2019.Rupp, M., Kern, S., Weber, T., Menges, T. D., Schnettler, R., Heiß, C., and Alt, V.:
Polymicrobial infections and microbial patterns in infected nonunions – A
descriptive analysis of 42 cases, BMC Infect. Dis., 20, 667, 10.1186/s12879-020-05386-9, 2020.Steinhausen, E., Lefering, R., Glombitza, M., Brinkmann, N., Vogel, C., Mester, B., and Dudda, M.: Bioactive glass S53P4 vs. autologous bone graft for filling defects in patients with chronic osteomyelitis and infected non-unions – a single center experience, J. Bone Joint Infect., 6, 73–83, 10.5194/jbji-6-73-2021, 2021.
Xie, Z., Liu, X., Jia, W., Zhang, C., Huang, W., and Wang, J.: Treatment of
osteomyelitis and repair of bone defect by degradable bioactive borate glass
releasing vancomycin, J. Control. Release., 139, 118–126,
2009.Zhou, C.-H., Ren, Y., Song, H.-J., Ali, A. A., Meng, X.-Q., and Xu, L.: One-stage
debridement and bone transport versus first-stage debridement and
second-stage bone transport for the management of lower limb post-traumatic
osteomyelitis, Journal of Orthopaedic Translation, 28, 21–27, 2021.