Oral and maxillofacial pathology
Differential impairment of vascularization and angiogenesis in bisphosphonate-associated osteonecrosis of the jaw-related mucoperiosteal tissue

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Objectives

Impaired vascularization in the etiopathology of aminobisphosphonate-associated osteonecrosis of the jaw (BONJ) is assumed, but evidence is lacking. This immunohistochemical study differentiated vascularization and angiogenesis in BONJ-adjacent mucoperiosteal tissue.

Study design

Twenty BONJ (after zoledronate treatment) and 20 control mucoperiosteal tissue samples were processed with an autostaining-based alkaline phosphatase-antialkaline phosphatase staining kit. Vascularization was assessed by CD31 staining and angiogenesis-related neovessels by CD105 staining. The ratio of stained capillary area to total area of visible field was assessed. Statistics included Bonferroni adjustment.

Results

CD31-stained microvessels were detected in each section and CD105-stained neovessels in each control. BONJ-adjacent mucoperiosteal tissue showed significantly fewer CD105-positive vessels in capillary areas (P < .05) than control samples. CD31-stained capillary area was not significantly reduced in mucoperiosteal BONJ-samples.

Conclusions

Angiogenesis is impaired in BONJ-related mucoperiosteal tissue, but vascularization remains unaffected. Vessel remodeling and neovessel formation is delayed in BONJ, resulting in impaired tissue regeneration of bisphosphonate-exposed oral mucosa.

Section snippets

Patients and material harvesting

This study included oral mucoperiosteal specimens from 40 patients. Of these, 20 specimens were from periodontal soft tissue adjacent to clinically and histologically confirmed BONJ of 20 consecutively treated patients undergoing radical sequestrectomy. Tissue specimens were taken as part of the tissue samples provided for routine histopathologic diagnostics. The necrotic tissue itself was excluded from the analysis. This study was approved by the local Ethical Committee of the University of

Results

Capillaries were seen in BONJ-related mucoperiosteal specimens and healthy jaw connective tissue. In normal jaw mucoperiosteal tissue and in BONJ-related samples, vascularization was clearly detectable by CD31-positive capillary staining in both groups (Figs. 1, A, and 2, A). No morphologic differences regarding the capillaries were seen between BONJ-affected and nonBP-exposed mucoperiosteal tissue. Vascular endothelial cell layers in both groups showed similar shapes and thicknesses. Newly

Discussion

These results show reduced angiogenesis in BONJ-related oral mucoperiosteal tissue compared with normal tissue, as shown by the significantly (P < .05) decreased CD105-positive relative capillary area. The inhibition of angiogenesis without significant effect on vascularization in BONJ was demonstrated for the first time in this study.

Reduced angiogenesis is consistent with the clinical finding of local dentoalveolar trauma-related incidence in BONJ and prolonged mucosal healing.26, 27 Whereas

References (41)

  • F.C. Cackowski et al.

    Osteoclasts are important for bone angiogenesis

    Blood

    (2010)
  • G. Mountzios et al.

    Markers of bone remodeling and skeletal morbidity in patients with solid tumors metastatic to the skeleton receiving the biphosphonate zoledronic acid

    Transl Res

    (2010)
  • H.L. Neville-Webbe et al.

    Bisphosphonates and RANK ligand inhibitors for the treatment and prevention of metastatic bone disease

    Eur J Cancer

    (2010)
  • T. Yoneda et al.

    Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology and Japanese Society of Oral and Maxillofacial Surgeons

    J Bone Miner Metab

    (2010)
  • M.R. Allen

    Bisphosphonates and osteonecrosis of the jaw: moving from the bedside to the bench

    Cells Tissues Organs

    (2009)
  • S.L. Ruggiero et al.

    Osteonecrosis of the jaws and bisphosphonate therapy

    J Dent Res

    (2007)
  • T. Hansen et al.

    Osteonecrosis of the jaws in patients treated with bisphosphonates—histomorphologic analysis in comparison with infected osteoradionecrosis

    J Oral Pathol Med

    (2006)
  • S. Agarwala et al.

    Alendronate in the treatment of avascular necrosis of the hip

    Rheumatology (Oxford)

    (2002)
  • M.A. Matos et al.

    The effect of zoledronate on bone remodeling during the healing process

    Acta Cir Bras

    (2007)
  • N. Amanat et al.

    Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair

    J Bone Miner Res

    (2007)

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    Supported by the ELAN-Fonds of the University of Erlangen-Nuremberg.

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