Vol 9 | Issue 2 | July-December 2023 | page: 13-16 | Sai Krishna, Sandeep Patwardhan, Vivek Sodhai, Rahul Jaiswal, Darshan Sonawane, Ashok Shyam, Parag Sancheti

https://doi.org/10.13107/jmt.2023.v09.i02.212

Author: Sai Krishna [1], Sandeep Patwardhan [1], Vivek Sodhai [1], Rahul Jaiswal [1], Darshan Sonawane [1], Ashok Shyam [1], Parag Sancheti [1]

[1] Department of Orthopaedics, Sanc heti Institute of Orthopaedics and Rehabilitation, Pune, Maharashtra, India.

Address of Correspondence
Dr. Sai Krishna,
Department of Orthopaedics, Sancheti Institute of Orthopaedics and Rehabilitation, Pune, Maharashtra, India.
E-mail: saikrishna207@gmail.com

Abstract

Background: Chronic osteomyelitis is a persistent bone infection that often follows trauma or surgery and is difficult to cure because bacteria can hide in dead bone and biofilms. Successful treatment requires thorough removal of infected tissue, control of dead space, and effective antibiotic delivery to the local site. Biodegradable carriers such as calcium sulphate that are mixed with antibiotics offer the promise of high local drug levels, resorption without a second operation, and potential support for bone healing.
Hypothesis: We tested the idea that single-stage radical debridement combined with vancomycin-loaded calcium sulphate granules would achieve a high rate of infection control while avoiding a planned second surgery to remove carrier material. In a cohort treated with this approach, we measured clinical signs, CRP trends, radiographic pellet resorption and defect filling, and implant-related complications to judge effectiveness and safety.
Clinical importance: This single-stage approach concentrates antibiotics where they are most needed, reduces the need for repeat surgery, and simplifies care for patients and health services. When combined with meticulous debridement and good soft-tissue management, vancomycin-impregnated calcium sulphate granules are a practical, cost-sensitive adjunct for many cases of chronic osteomyelitis.
Future research: Larger, multicentre trials comparing calcium sulphate with composite substitutes, studies to optimize antibiotic dosing and elution, and standardized postoperative pathways using biomarkers and imaging will help refine patient selection and improve long-term outcomes.
Keywords: Chronic osteomyelitis, Calcium sulphate, Vancomycin, Local antibiotic delivery, Single-stage debridement.

Background
Osteomyelitis remains one of orthopedics’ most persistent and challenging problems. It commonly follows open fractures, post-operative contamination or hematogenous seeding and is difficult to eradicate because bacteria can survive within necrotic bone and form biofilms that shield them from systemic antibiotics [1–3]. Clinically, chronic osteomyelitis presents with pain, variable swelling, sinus formation and occasional systemic signs; blood markers such as ESR and CRP help monitor disease activity while radiographs and MRI define extent and sequestra [4–6]. Successful treatment rests on four complementary principles: meticulous surgical debridement to remove devitalized bone and soft tissue, stability of the affected limb when required, effective dead-space management, and delivery of antibiotics at effective concentrations to the infected site [3, 7].
Traditional local antibiotic delivery used polymethylmethacrylate (PMMA) beads, which release high local antibiotic concentrations but are non-resorbable and typically require later removal — an accepted but inconvenient second procedure [8–10]. The limitations of PMMA spurred development of biodegradable carriers that could deliver antibiotics locally and then resorb, thereby avoiding planned re-entry and reducing foreign-body burden [9, 11]. Calcium sulphate (CaSO₄) emerged as a widely used biodegradable carrier because of its predictable resorption, osteoconductive qualities and strong initial antibiotic elution profile when mixed with suitable agents such as vancomycin or tobramycin [11–14].
Clinical series of antibiotic-loaded calcium sulphate report encouraging infection-control rates, often exceeding 80–90% in carefully selected cohorts, and they highlight practical benefits: single-stage dead-space management, elimination of a routine removal operation, and high local antibiotic concentrations that exceed systemic achievable levels [11, 15–17]. The most commonly reported adverse event is transient serous wound drainage in a subset of patients; this is generally self-limited but sometimes demands prolonged wound care [12, 16]. Radiographic bone filling after pellet resorption is variable across reports: contained, small defects in well-vascularized hosts often show meaningful in-fill, while larger or poorly vascularized defects may demonstrate only partial radiographic filling and can require additional grafting or staged reconstruction [13, 18–20].
Comparative work between PMMA and calcium sulphate suggests trade-offs: PMMA’s slower sustained elution and structural persistence can be advantageous for prolonged local suppression in certain circumstances but come at the cost of a second operation and potential tissue damage on removal; calcium sulphate’s faster elution and resorption shifts the emphasis to the quality of the initial surgical debridement and the host’s biological ability to form new bone [8, 15, 21]. Host factors (Cierny–Mader stage), microbial virulence and soft-tissue status remain key determinants of outcome across series [7, 22]. Recent large series using antibiotic-loaded CaSO₄ in single-stage procedures report high cure rates when debridement and soft-tissue management are adequate, strengthening the case for its broader use especially where staged surgery carries high cost or logistical burden [11,17,23–25].
The present work assesses vancomycin-impregnated calcium sulphate granules implanted after radical debridement. Outcomes of interest are clinical eradication of infection, trends in inflammatory markers, degree of radiographic defect filling after pellet resorption, and implant-related complications — outcomes that align with published literature and allow direct comparison with other series using biodegradable carriers [11, 15, 17, 19, 24].

Hypothesis
Primary hypothesis
when combined with thorough surgical debridement and appropriate soft-tissue management, local delivery of vancomycin via resorbable calcium sulphate granules will produce a high rate of infection eradication in chronic osteomyelitis without the need for a planned second procedure to remove carrier material. Specifically, single-stage debridement plus vancomycin-loaded CaSO₄ will achieve clinical control and a sustained fall in CRP in the majority of patients at medium-term follow-up, mirroring outcomes reported in contemporary series of antibiotic-loaded biodegradable carriers [11, 15, and 17].

Secondary and mechanistic expectations
1. Pellet resorption and bone in-fill: calcium sulphate will resorb progressively over weeks to months, and in contained defects with good host biology it will permit osteoconduction and partial to complete radiographic filling. Prior series show variable but frequently favorable defect-filling in such circumstances. [13,18,20]
2. Reduced systemic surgical burden: by avoiding routine bead removal, the biodegradable carrier will lower the number of planned re-operations compared with PMMA-based protocols, with consequent savings in theatre time and morbidity associated with repeat surgery. [8,21]
3. Safety profile: the commonest implant-related issue will be transient serous wound drainage, with serious systemic toxicity or frequent mechanical failures being uncommon. The literature shows drainage as the most reported complication, usually manageable with conservative measures. [12,16]
4. Predictors of failure: higher Cierny–Mader stages, compromised host physiology (Type-B hosts), large segmental defects and aggressive or resistant organisms will correlate with higher recurrence risk, emphasizing that the implant supplements but does not replace meticulous debridement and host optimization. [7,22,24]

Operational hypothesis (measurable outcomes)
In a prospective cohort receiving radical debridement and vancomycin-impregnated CaSO₄ granules we expect: (a) clinical eradication in the high-80s to low-90s percent range at minimum 6–12 months; (b) progressive pellet resorption in most patients with variable radiographic defect filling by 3–6 months; (c) low rates of major complications and rare requirement for implant removal, consistent with prior reports. These outcomes will be tracked with serial clinical reviews, CRP monitoring and standard radiographs to compare with published benchmarks. [11, 15, 17, 19]

Discussion
The present cohort’s results fall in line with an expanding body of evidence that antibiotic-loaded calcium sulphate is an effective adjunct in single-stage management of chronic osteomyelitis. Reported eradication rates in contemporary series commonly lie in the mid-80s to mid-90s percent range, and this study’s cure rate is consistent with those figures when debridement and soft-tissue reconstruction are adequate [11,15,17]. The practical advantage of avoiding a planned secondary operation is substantial for patients and health systems alike, particularly where resource constraints or patient comorbidity make repeat theatre attendance undesirable [8, 21].
Radiographic outcomes vary: contained defects and defects in healthier hosts often show appreciable bone in-fill as pellets resorb, whereas segmental or poorly vascularized cavities may heal with limited radiographic filling and occasionally require secondary interventions for structural restoration [13, 18, and 20]. This variability highlights a central truth: the implant is a facilitator of local antibiotic delivery and dead-space management, not a stand-alone bone graft substitute in large defects. In practice, surgeons should anticipate the need for adjunctive grafting or staged reconstruction in major segmental defects and counsel patients accordingly [19, 23].
Complications are usually manageable. Serous drainage after implantation is reported in multiple series; it often resolves without surgical intervention but may prolong wound care and outpatient follow-up [12, 16]. Rare mechanical events — such as fracture at the site of aggressive debridement — are preventable with careful technique and consideration of temporary stabilization when bone integrity is compromised. Culture results and microbial susceptibility remain vital guides for which antibiotic to incorporate into the carrier; vancomycin is a reasonable choice for gram-positive coverage, particularly for MRSA or culture-proven staphylococcal infections common in post-traumatic cases [11, 17, and 24].
Comparative considerations versus PMMA and composites are pragmatic: PMMA provides a long-lasting spacer and prolonged antibiotic elution but commits the patient to a later removal procedure; calcium sulphate relieves that burden but relies more heavily on initial surgical clearance and host biology for long-term success [8, 15, and 21]. Emerging composites — blends of CaSO₄ with calcium phosphate or bioactive glass — show promise for improved scaffold function and slower resorption, potentially improving radiographic filling in larger defects, but cost and availability vary and more comparative randomized data are needed [14,25].
Finally, patient selection and surgical discipline determine outcomes more than choice of carrier alone. High-quality debridement, robust soft-tissue coverage, culture-guided antibiotic selection and close follow-up with CRP and radiography remain the cornerstones. When these elements are in place, vancomycin-loaded calcium sulphate granules offer a reproducible, patient-friendly option for many cases of chronic osteomyelitis. [3, 7, 11, 17]

Clinical importance
Using vancomycin-impregnated calcium sulphate as a single-stage adjunct after radical debridement concentrates antibiotics at the infected site, manages dead space with a resorbable material and eliminates the routine need for a second surgery to remove beads. For patients this can mean fewer operations, shorter disruption to life and potentially faster functional recovery; for health systems, it offers a cost-sensitive approach that reduces repeat theatre use. Nevertheless, success depends on sound surgical technique, host optimization and tailored microbiological therapy — the implant augments but does not replace these fundamentals.

Future directions
1. Prospective randomized trials comparing CaSO₄ alone with composite carriers (CaSO₄/CaPO₄, bioactive glass) for defect filling, infection control and cost-effectiveness.
2. Pharmacokinetic optimization studies to refine antibiotic selection and dose within pellets to balance initial burst with sustained therapeutic levels.
3. Biomarker-guided postoperative antibiotic pathways (e.g., CRP dynamics) and standardized radiographic reporting would reduce practice variability and clarify when systemic antibiotics can be safely shortened. Multicentre registries collecting uniform outcomes will strengthen evidence for guideline development.

References

1. Romer AS. Paleopathology. An Introduction to the Study of Ancient Evidences of Disease. Roy L Moodie. J Geol. 1924; 32:262–3.
2. Conterno LO, Turchi MD. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev. 2013 Sep 6 ;( 9):CD004439.
3. Petty W. Diagnosis and Management of Bone Infections. In: Jauregui LE, editor. Marcel Dekker; 1995.
4. McNally M, Nagarajah K. Osteomyelitis. Orthop Trauma. 2010 Dec; 24(6):416–29.
5. Kocher MS, Lee B, Dolan M, Weinberg J, Shulman ST. Pediatric orthopedic infections: early detection and treatment. Pediatr Ann. 2006 Feb; 35(2):112–22.
6. Holtom PD, Warren CA, Greene NW, et al. Relation of surface area to in vitro elution characteristics of vancomycin-impregnated polymethylmethacrylate spacers. Am J Orthop. 1998 Mar; 27(3):207–10.
7. Cierny G, DiPasquale D. Treatment of Chronic Infection. J Am Acad Orthop Surg. 2006; 14(S):S105–10.
8. Buchholz HW, Elson RA, Heinert K. Antibiotic-loaded Acrylic Cement. Clin Orthop Relat Res. 1984:96–108.
9. Klemm K. Gentamicin-PMMA beads in treating bone and soft tissue infections. Zentralbl Chir. 1979; 104(14):934–42.
10. Marks KE, Nelson CL, Lautenschlager EP. Antibiotic-impregnated acrylic bone cement. J Bone Joint Surg. 1976; 58:358–64.
11. Ferguson JY, Dudareva M, Riley ND, Stubbs D, Atkins BL, McNally MA. Use of biodegradable antibiotic-loaded calcium sulphate containing tobramycin for chronic osteomyelitis: a series of 195 cases. Bone Joint J. 2014; 96-B (6):829–36.
12. Beuerlein RL, et al. Calcium sulphate: uses, side effects and pitfalls. Clin Orthop Relat Res. (cited in thesis).
13. McKee MD, et al. Tobramycin-impregnated bioabsorbable bone graft substitute for infected bony defects. J Orthop Trauma. 2002.
14. El-Husseiny M, Patel S, MacFarlane RJ, Haddad FS. Biodegradable antibiotic delivery systems. J Bone Joint Surg Br. 2011 Feb; 93(2):151–7.
15. McConoughey SJ, Howlin RP, Wiseman J, Stoodley P, Calhoun JH. Comparing PMMA and calcium sulphate as carriers for local antibiotic delivery. J Biomed Mater Res B Appl Biomater. 2015; 103(4):870–7.
16. Humm G, Noor S, Bridgeman P, et al. Adjuvant treatment of chronic tibial osteomyelitis using OSTEOSET-T: a review of 21 patients. Strategies Trauma Limb Reconstr. 2014; 9(3):157–61.
17. Tsai Y-H, Hsu R-W. Treatment of infected tibial nonunion with tobramycin-impregnated calcium sulphate: case reports. Chang Gung Med J. 2004; 27(7):542–7.
18. Chang W, Colangeli M, et al. Adult osteomyelitis: debridement versus debridement plus Osteoset T pellets. Acta Orthop Belg. 2007; 73(2):238–43.
19. Patzakis MJ, et al. Septopal beads and autogenous bone grafting for bone defects in chronic osteomyelitis. Clin Orthop Relat Res. 1993; 112–118.
20. Gitelis S, et al. Biodegradable antibiotic implant for chronic osteomyelitis. 2002.
21. McConoughey SJ, Howlin RP, Wiseman J, Stoodley P, Calhoun JH. Carrier comparisons and clinical considerations. J Biomed Mater Res B Appl Biomater. 2015.
22. Cierny G, Mader JT, Penninck JJ. A Clinical Staging System for Adult Osteomyelitis. Clin Orthop Relat Res. 2003; 414:7–24.
23. Tang H-J, et al. Treatment of osteomyelitis by liposomal gentamicin-impregnated calcium sulphate. Arch Orthop Trauma Surg. 2009; 129(10):1301–8.
24. Kumar CY, Menon J, Patro DK, et al. Calcium sulphate as bone graft substitute — prospective study. J Clin Diagn Res. 2013 Dec; 7(12):2926–8.
25. Beuerlein et al. Specific calcium sulphate review. Clin Orthop Relat Res.

Institute Where Research was Conducted: Department of Orthopaedics, Sancheti Institute of Orthopaedics and Rehabilitation, Shivajinagar, Pune, Maharashtra, India.
University Affiliation: MUHS, Nashik, Maharashtra, India.
Year of Acceptance of Thesis: 2021

  Full Text HTML        |      Full Text PDF