Suppurative osteomyelitis, bisphosphonate induced osteonecrosis, osteoradionecrosis: a blinded histopathologic comparison and its implications for the mechanism of each disease

Abstract

Statistically, significant numbers of central bone specimens of suppurative osteomyelitis of the jaws (SOJ), bisphosphonate induced osteonecrosis of the jaws (BIONJ), and osteoradionecrosis of the jaws (ORNJ) were compared. All three evidenced the common finding of necrotic bone with empty osteocytic lacunae, Haversian and Volkmann canals, but each showed a distinctive histopathologic pattern indicating a different disease mechanism and treatment options. Suppurative osteomyelitis was characterized by intense marrow inflammation and marrow vessel thrombosis with retention of viable osteoclasts and periosteum. Bisphosphonate induced osteonecrosis was characterized by an empty marrow space with empty Howship’s lacunae and an absence of osteoclasts but viable periosteum. Osteoradionecrosis was characterized by a collagenous hypocellular, hypovascular marrow space and nonviable periosteum. Histologic evidence in SOJ indicates a microorganism provoked intense inflammation and marrow vascular thrombosis creating an environment conducive to continual bacterial proliferation. BIONJ is seen as a non-inflammatory drug toxicity to bone by osteoclastic death leading to over suppression of bone renewal, and ORN as another non-inflammatory condition caused by a high linear energy transfer that impairs or kills numerous cell types in the field of radiation including periosteum, bone, and all soft tissue.

Suppurative osteomyelitis of the jaws (SOJ), bisphosphonate induced osteonecrosis of the jaws (BIONJ), and osteoradionecrosis of the jaws (ORNJ) have necrotic bone in common, but each represents a separate clinical disease and requires a different treatment approach. These diseases may be confused clinically due to similar symptoms and radiographic findings. BIONJ and ORNJ can become secondarily infected obscuring the true aetiology of the disease.

The purpose of this study was to compare the histopathologies of these three diseases in a blinded fashion using central bone specimens resected from each disease entity and correlate it to the current theories concerning the mechanism of each disease.

Materials and methods

Debrided or resected block bone specimens were obtained from 23 cases of SOJ, 37 cases of BIONJ, and 45 cases of ORNJ from 1 January 2005 to 30 December 2010. Materials were exempt from institutional review board approval as names and medical record were redacted from the study materials. Criteria for the diagnosis of SOJ were an absence of radiotherapy and bisphosphonate use; an identified source of infection; and the presence of pus, or radiographic evidence of osteolysis. Criteria for the diagnosis of BIONJ were the presence of exposed bone in the maxilla or mandible that persisted for at least 8 weeks with the use of a systemic bisphosphonate in the absence of local radiation . Criteria for the diagnosis of ORNJ were the presence of exposed bone in the maxilla or mandible that persisted for at least 8 weeks in a patient who received at least 6000 cGy of local radiotherapy and who did not receive a bisphosphonate . All specimens were processed with a slow decalcification process in 5% formic acid prior to embedding in paraffin. Histopathology slides were cut in 6 μm sections and stained with haematoxylin and eosin (H–E). Each specimen was examined using three cuts through the paraffin embedded block.

Results

Suppurative osteomyelitis

All 23 cases (100%) of SOJ identified necrotic bone as evidenced by empty osteocytic lacunae, absence of osteoblastic rimming, and empty Haversian canals. All 23 cases (100%) identified inflammatory cells in the marrow space judged to be heavy 13/23 (57%), moderate 7/23 (30%), and slight 3/23 (13%). The inflammatory cells were a mixture of neutrophils, plasma cells, some histiocytes, and lymphocytes with no pattern or predominance consistently noted ( Fig. 1 ). Osteoclasts were noted to be present in 22/23 (96%) of cases. The osteoclasts were noted to be small with 2–4 nuclei and were actively resorbing necrotic bone ( Fig. 2 ). Although the mineralized portion of bone lacked blood vessels in the Haversian and Volkmann canals, capillaries, arterioles, and venules were noted in the marrow space. 21/23 (91%) specimens identified hyperemia or thrombosis in these marrow space vessels ( Fig. 3 ). Microorganisms were seen in 8/23 (33%) of cases. Reactive viable bone was noted in 17/23 of cases (74%) at the surface.

Fig. 1
Necrotic trabecular bone with acute and chronic inflammatory cells within the marrow space of suppurative osteomyelitis.

Fig. 2
Small osteoclasts with 2–4 nuclei were seen to resorb necrotic bone in suppurative osteomyelitis.

Fig. 3
Hyperemia and thrombosis of marrow blood vessels were seen along with inflammation in suppurative osteomyelitis.

Bisphosphonate induced osteonecrosis

All 37 cases (100%) of BIONJ identified necrotic bone as evidenced by empty osteocytic lacunae, an absence of osteoblastic rimming and empty Haversian systems and Volkmann canals. No cases (0%) showed inflammatory cells or blood vessels in the marrow space. The entire marrow space was found to be acellular in all specimens and devoid of extracellular collagen or cellular products ( Fig. 4 ). In 9 of the 37 specimens, various amounts of cellular debris were noted. There were frequent scalloped bone edges representing empty Howship’s lacunae, the size and depth of which varied. Microorganisms were seen only on the surface of the bone in 28 of 37 (76%) specimens ( Fig. 5 ). There was reactive bone in 30/37 (81%) specimens and viable periosteum could be seen on 10/10 (100%) specimens in which the periosteum was still preserved ( Fig. 6 ).

Fig. 4
Necrotic bone and empty marrow spaces, devoid of inflammatory cells or fibrosis were seen in all specimens of bisphosphonate induced osteonecrosis. Also noted was scalloping of bone edges suggestive of interrupted Howship’s lacunae.

Fig. 5
Surface colony of actinomyces is seen together with empty marrow spaces without microorganisms in a bisphosphonate induced osteonecrosis specimen.

Fig. 6
In areas where mucosa remains attached to the necrotic bone in bisphosphonate induced osteonecrosis there remains viable periosteum.

Osteoradionecrosis

All 45 specimens (100%) identified necrotic bone as evidenced by empty osteocytic lacunae, an absence of osteoblastic rimming, and empty Haversian systems and Volkmann canals. There was a notable absence of inflammatory cells and normal marrow elements or fat cells throughout the marrow. Instead, the marrow mainly consisted of acellular collagen with only a rare cell nuclei noted ( Fig. 7 ). There was also an absence of functioning blood vessels in all specimens (100%). Remnants of old blood vessels could be seen as devoid of endothelial and adventitial cells leaving only a ring of basal lamina ( Fig. 8 ). Microorganisms were seen only on the surface of the bone in 26 of the 45 specimens (58%). Periosteum was preserved in 22/45 specimens (49%). In all of these 22 specimens, the periosteum was seen to be acellular and avascular. Surface debris was noted in 18/45 specimens (40%).

Fig. 7
Necrotic bone with prominent marrow fibrosis was seen in all cases of osteoradionecrosis. Note the absence of the scalloping at bone edges that is seen in specimens of bisphosphonate induced osteonecrosis.

Fig. 8
Empty remnant of a blood vessel with absence of endothelial cells but residual basal lamina is seen in cases of osteoradionecrosis. This radiotherapy effect is similar to the marrow fibrosis where long gone fibroblasts have left residual collagen.

Results

Suppurative osteomyelitis

All 23 cases (100%) of SOJ identified necrotic bone as evidenced by empty osteocytic lacunae, absence of osteoblastic rimming, and empty Haversian canals. All 23 cases (100%) identified inflammatory cells in the marrow space judged to be heavy 13/23 (57%), moderate 7/23 (30%), and slight 3/23 (13%). The inflammatory cells were a mixture of neutrophils, plasma cells, some histiocytes, and lymphocytes with no pattern or predominance consistently noted ( Fig. 1 ). Osteoclasts were noted to be present in 22/23 (96%) of cases. The osteoclasts were noted to be small with 2–4 nuclei and were actively resorbing necrotic bone ( Fig. 2 ). Although the mineralized portion of bone lacked blood vessels in the Haversian and Volkmann canals, capillaries, arterioles, and venules were noted in the marrow space. 21/23 (91%) specimens identified hyperemia or thrombosis in these marrow space vessels ( Fig. 3 ). Microorganisms were seen in 8/23 (33%) of cases. Reactive viable bone was noted in 17/23 of cases (74%) at the surface.

Jan 26, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Suppurative osteomyelitis, bisphosphonate induced osteonecrosis, osteoradionecrosis: a blinded histopathologic comparison and its implications for the mechanism of each disease
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