Autopsy-Based Assessment of Extent and Type of Osteomyelitis in Advanced-Grade Sacral Decubitus Ulcers: A Histopathologic Study

Decubitus ulcers constitute a serious medical problem that is most commonly encountered in elderly people, often in association with hospitalization or institutionalization in senior citizens' or nursing homes.1–4 Patients with decubitus ulcers have a markedly increased risk of dying.5 This risk is due to potentially fatal complications, such as protein loss, volume depletion, or systemic inflammatory response (sepsis). In many cases, however, the development of advanced-grade decubitus ulcers, and thus their potentially fatal complications, are preventable.6 

One potentially life-threatening complication of advanced-grade decubitus ulcers is the development of sepsis.7,8 Septic manifestations resulting from decubitus ulcers have been associated with a mortality rate of up to 50%.7 Systemic inflammatory complications have been reported to originate not only from soft tissue infection, but also from osteomyelitis due to involvement of bone tissue in the ulcerous lesions.1,2,7,8 However, it is difficult to differentiate between soft tissue infection alone and accompanying bone infection as the source of sepsis by clinical diagnostic means.9,10 Furthermore, the available imaging techniques are not sufficient to distinguish between infectious and pressure-induced osseous changes, such as fibrosis and reactive bone formation.11 Because the presence and extent of decubitus ulcer–associated osteomyelitis affect the extent of both surgical management and antibiotic treatment, the establishment of a correct diagnosis is of major importance in instituting the most effective treatment. Earlier clinicopathologic studies have investigated the histopathologic features of decubitus ulcer–associated cutaneous, subcutaneous, and osseous changes.11–14 However, a systematic approach toward the osteopathology of advanced-grade decubitus ulcers using human autopsy specimens is, to the best of our knowledge, missing in the literature. The purposes of the present study were to fill this gap and to provide new insights into the extent and type of osteomyelitis in advanced-grade decubitus ulcers.

A total of 28 cases of advanced-grade decubitus ulcers found in individuals subjected to medicolegal autopsies at the Institute of Legal Medicine, University Hospital of Hamburg, Hamburg, Germany, were investigated. Only grade IV decubitus ulcers (as defined by Shea15) with visible bone tissue in the depth of the lesion were included in the study. The 28 cases included deceased patients (20 women, 8 men; age range, 57–96 years; mean age, 83.3 years) with grade IV decubitus ulcers localized in the coccygeal area. Cone-shaped specimens of the affected part of the os sacrum, measuring 2.5 × 1.5 cm, were prepared. The undecalcified preparation after plastic embedding, as described by Hahn et al,16 was used to allow artifact-free preparation of spongy and cortical bone tissue, as well as cellular structures. In brief, after fixation, dehydration, and fat removal, the specimens were submerged in methylmethacrylate for 24 hours. Polymerization was carried out for 24 to 48 hours at 36°C in gelatin capsules, using a mixture of methylmethacrylate, nonylphenolpolyglocoletheracetate as a softener and benzoyl peroxide as the polymerization starter. After polymerization, capsules and methylmethacrylate were removed, and the blocks were cut while moist to avoid compression artifacts. After mounting and deplastination, the sections were stained using Goldner stain, toluidine blue, and a modification of Kossa and Giemsa stains.

The causes of death were pneumonia in 12 patients, heart failure in 10, advanced-stage tumors in 3, sepsis due to gangrene of the leg in 1 patient, and pancreatic failure and urosepsis in 1 case each. Sepsis complicating an advanced-grade decubitus ulcer leading to fatal outcome was considered a potential differential diagnosis in 1 case only.

Due to the relatively advanced age of the patients included in our study, marked rarefaction of the spongy bone tissue was present, but signs of metabolic bone disease, that is, osteomalacia, were not found in any of the cases. In most cases (n = 15), no osteomyelitic changes could be detected. Chronic inflammation was found in all cases with osteomyelitis. In addition, acute inflammatory cells were present in 7 cases. The pathomorphologic changes in the direct vicinity of the decubitus ulcers were divided into 4 groups. Group 4, in which osteomyelitis was present, was further divided into 2 subgroups, depending on the type of osteomyelitis (exclusively chronic or a combination of acute and chronic osteomyelitic changes). The 4 groups were defined as described in the follow sections.

In this group, the cortical layer of the os sacrum was intact, and bone tissue was not involved in decubitus ulcer formation. The ulcer region showed full-thickness destruction of all skin layers with obliterated cellular details, as described by Witkowski and Parish,14 but no signs of inflammation could be detected. Trabeculae in the spongy bone were irregular, and edema of the medullary cavity was frequently present.

In this group, the cortex of the os sacrum was destroyed and had a spongelike rather than compact appearance. In the spongy bone, granulation tissue and increased osteoclast activity, as well as sites of reactive new bone formation, were seen. Microcallus formation was frequently present (Figure 1). Edema of the medullary cavity was also frequently observed. In isolated cases, parts of the medullary cavity were necrotic.

Bone tissue was involved in decubitus ulcer formation in only 1 of the cases investigated, but no osteomyelitic changes were detectable despite extensive acute suppurative soft tissue inflammation (Figure 2). Bone tissue alterations were as described for group 2.

Apart from destruction of the cortex and presence of granulation tissue, this group was characterized by an infiltration with lymphocytes and plasma cells (Figure 3). Mild edema of the medullary cavity was present in most of these cases. Chronic osteomyelitic alterations affected only the superficial, subcortical parts of the os sacrum. Involvement of deeper parts of the medullary cavity was not seen in any of the cases.

Chronic osteomyelitic changes were as described for group 4a. In 7 cases, an accompanying acute osteomyelitis was found, as diagnosed by the presence of neutrophils. Acute osteomyelitic changes were mild and confined to small areas in all cases. No extensive suppurative inflammation with destruction of wide parts of the bone was seen.

We have, to the best of our knowledge, carried out the first autopsy-based systematic study regarding the histopathology of osseous structures involved in grade IV decubitus ulcers. Compared to clinicopathologic studies, investigations based on autopsy material allow a more precise assessment of the extent of bone involvement, as well as a clearer differentiation between the types of osteomyelitis and pressure-induced osseous lesions. Based on the histopathologic findings in our study, we were able to divide the observed osteomyelitic changes into 4 distinct groups. In more than half of the cases (n = 15), no signs of osteomyelitis were detectable (groups 1–3). In agreement with the results of Darouiche et al,11 who found chronic osteomyelitis in 17% of the cases they evaluated, but no signs of acute inflammation in their pathologic investigations of bony structures involved in advanced-grade decubitus ulcers,11 we could detect chronic inflammatory cells in all cases in which osteomyelitis was present. In addition, we found an accompanying mild acute osteomyelitis in 7 of these cases. Pressure-induced changes, namely, fibrosis, edema of the medullary cavity, or reactive bone formation, were present in all cases irrespective of the presence and type of osteomyelitis, even in cases in which the cortical bone layer was intact (group 1).

Systemic infectious complications caused by bacterial infection of grade IV pressure sores have been reported frequently, affecting the mortality rate.1,2,8,12 Especially in septic complications of advanced-grade decubitus ulcers persisting over a long period, mortality rates of up to 50% have been described in the clinical literature.7 Systemic inflammatory complications have been reported to originate from osteomyelitis in grade IV decubitus ulcers.1,2,7,8,13 Sepsis was present in only 2 cases investigated in the present study; in one of these cases, the sacral decubitus ulcer was considered a possible source of systemic inflammation. Thus, it is not possible to draw conclusions about sepsis resulting from infected grade IV decubitus ulcers. For this purpose, histopathologic studies of grade IV decubitus ulcers from deceased patients with sepsis should be performed for comparison.

Regarding the means of diagnosis in cases of suspected osteomyelitis, it is a well-established fact that osseous destruction and inflammation can easily be overestimated by clinical assessment alone. By clinical diagnostic means, even with sensitive imaging techniques, such as computed tomography or technetium 99^mTc-scintiscanning, it is impossible in most cases to distinguish between osteomyelitis and pressure-induced osseous changes in inflammatory processes confined to fat and muscle tissue.9–13 Likewise, bacteriology is not sufficient to distinguish a bona fide osteomyelitis from merely pressure-induced osseous repair response.11 Occurrence of decubitus ulcer–associated osteomyelitis has been reported with frequencies ranging from 17%10 to 58%.17 The presence of extensive osteomyelitis in grade IV decubitus ulcers strongly affects the efficiency of decubitus ulcer therapy. The complication rate and the duration of hospitalization have been shown to be much higher in patients with decubitus ulcer–associated osteomyelitis.18 Thus, analysis of bone biopsies has been recommended in cases in which clinical parameters for osteomyelitis yield negative results but suspicion of osteomyelitis remains,10 and other authors even suggest that biopsy should be performed routinely.11 For patients without sepsis, our results stand in marked contrast to this concept. We found that in more than half of the cases with grade IV decubitus ulcers, no osteomyelitic changes were present. When osteomyelitis was found, the alterations were very mild and basically confined to the superficial parts of the os sacrum. As such minor alterations do not widely affect the therapeutic strategy, and as, on the other hand, they might easily escape detection even if biopsy is performed, we propose that collection of a bone biopsy is not necessary when sepsis is not present. Whether this is also true for patients with sepsis remains to be elucidated. Likewise, in patients without sepsis, restraint should be exercised with osteotomy; even when osteomyelitis is present, only superficial parts of the bone are affected in a considerable proportion of cases.

The results of this study suggest that the incidence of severe osteomyelitis in the bone underlying grade IV sacral decubitus ulcers in patients without sepsis is low. Sections of the sacral bone in such cases commonly show bone destruction, repair response, and superficial chronic or mixed acute and chronic osteomyelitis, but no severe osteomyelitis. Whether sections of this bone in cases with sepsis show a significant incidence of severe osteomyelitis and might reveal the source of sepsis is a question worthy of study. Furthermore, our results lead to the recommendation that in cases of advanced-grade decubitus ulcers in patients without sepsis, restraint should be exercised in the collection of bone biopsies, as the observed changes are of minor consequence when establishing the therapeutic strategy.