Mark A. Reynolds

Background:Intra‐oral minocycline staining of alveolar bone and teeth is well‐described in the literature. Minocycline‐induced discoloration of oral soft tissues is less common and has been often attributed to staining of the underlying bone.Aim:This report documents the clinical and histopathologic features of a case of actual oral soft tissue minocycline‐induced pigmentation. The patient, a 45‐year‐old Caucasian female, presented with pigmentation of the gingiva, lips, and nail beds of recent onset. The past medical history revealed initiation of minocycline therapy 6 months earlier for dermatological concerns. Histopathologic examination of biopsy specimens from the gingiva and lip showed evidence of increased melanin/melanocytes in the epithelium and melanin/melanophages in the connective tissue. A working diagnosis of drug‐associated pigmentation was determined and the patient discontinued immediately minocycline therapy. Nine months after cessation of minocycline the patient exhibited a marked reduction in pigmentation.Conclusion:Systemic minocycline treatment has the potential to induce significant and esthetically objectionable discoloration of the gingiva and oral mucosa. A brief review of the literature is presented to help understand this uncommon finding that should be included in the differential diagnosis of spontaneous discoloration of intra‐oral soft tissues.

Alterations in sex steroids during pregnancy are associated with the development and exacerbation of reactive lesions involving the gingiva. Currently, few experimental animal models similar to humans are available to examine regulatory pathways involving sex steroids and the periodontium. In the present study, we used the baboon as a novel experimental model for the study of the regulatory actions of estrogen on the periodontium during pregnancy. Pregnant baboons (N = 5) were administered the potent, highly specific aromatase inhibitor CGS 20267 (2 mg/day subcutaneously) daily on days 60 through 165 of gestation (term = 184). Untreated females (N = 10) and females (5) concomitantly administered aromatase inhibitor and estradiol benzoate (2.0 mg/day each subcutaneously) served as controls. Gingival biopsies were taken between days 145 and 165 of gestation. Administration of CGS 20267 in all females suppressed maternal serum concentrations of estradiol by 95% and induced the development of an exuberant papillomatous enlargement of the gingiva by gestational day 110, with the most prominent development involving the labial aspects of the anterior sextants. None of the untreated pregnant controls or females concomitantly administered aromatase inhibitor and estradiol benzoate developed gingival overgrowth. Thus, estradiol alone prevented the onset of gingival overgrowth induced by estrogen suppression. In all baboons, discontinuation of the aromatase inhibitor at time of cesarean section resulted in spontaneous regression and resolution of the papillomatous hyperplasia within 4 to 6 weeks. Clinically, the gingival papillary overgrowth was erythematous and edematous, with a propensity toward spontaneous subgingival hemorrhage. Histologically, the biopsy specimens demonstrated hyperplasia of the epithelium typified by mild hyperkeratosis, acanthosis, and elongation and isolated anastamoses of rete ridges. Subjacent to the intact epithelium was a loose connective tissue stroma with isolated areas of inflammatory cell infiltrate. Special stains verified the presence of isolated bacterial biofilms; however, no evidence of fungal filaments was present. Histological features suggestive of viral infection were notably absent in the epithelium. No evidence of viral particles or capsids was identified using transmission electron microscopy. Reverse transcription polymerase chain reaction analysis, using a panel of degenerate primers, was negative for papilloma family viruses. These results are consistent with a significant role for estrogen during primate pregnancy in the regulation of cellular proliferation and differentiation within the gingiva. The baboon represents an important experimental model for studying the regulatory actions of estrogen on the periodontium during pregnancy.

Background: Bone replacement grafts (BRG) are widely used in the treatment of periodontal osseous defects; however, the clinical benefits of this therapeutic practice require further clarification through a systematic review of randomized controlled studies. Rationale: The purpose of this systematic review is to access the efficacy of bone replacement grafts in proving demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone. Focused Question: What is the effect of bone replacement grafts compared to other interventions on clinical, radiographic, adverse, and patient‐centered outcomes in patients with periodontal osseous defects? Search Protocol: The computerized bibliographical databases MEDLINE and EMBASE were searched from 1966 and 1974, respectively, to October 2002 for randomized controlled studies in which bone replacement grafts were compared to other surgical interventions in the treatment of periodontal osseous defects. The search strategy included screening of review articles and reference lists of retrieved articles as well as hand searches of selected journals. Inclusion criteria: All searches were limited to human studies in English language publications. Exclusion criteria: Non‐randomized observational studies (e.g., case reports, case series), publications providing summary statistics without variance estimates or data to permit computation, and studies without BRG intervention alone were excluded. Data Collection and Analysis: The therapeutic endpoints examined included changes in bone level, clinical attachment level, probing depth, gingival recession, and crestal resorbtion. For purposes of meta‐analysis, change in bone level (bone fill) was used as the primary outcome measure, measured upon surgical re‐entry or transgingival probing (sounding). Main Results: Forty‐nine controlled studies met eligibility criteria and provided clinical outcome data on intrabony defects following grafting procedures. Seventeen studies provided clinical outcome data on BRG materials for the treatment of furcation defects Reviewers' Conclusions: With respect to the treatment of intrabony defects, the results of meta‐analysis supported the following conclusions: 1) bone grafts increase bone level, reduce crestal bone loss, increase clinical attachment level, and reduce probing depth compared to open flap debridement (OFD) procedures; 2) No differences in clinical outcome measures emerge between particulate bone allograft and calcium phosphate (hydroxyapatite) ceramic grafts; and 3) bone grafts in combination with barrier membranes increase clinical attachment level and reduce probing depth compared to graft alone. With respect to the treatment of furcation defects, 15 controlled studies provided data on clinical outcomes. Insufficient studies of comparable design were available to submit data to meta‐analysis. Nonetheless, outcome data from these studies generally indicated positive clinical benefits with the use of grafts in the treatment of Class II furcations. With respect to histological outcome parameters, 2 randomized controlled studies provide evidence that demineralized freeze‐dried bone allograft (DFDBA) supports the formation of a new attachment apparatus in intrabony defects, whereas OFD results in periodontal repair characterized primarily by the formation of a long junctional epithelial attachment. Multiple observational studies provide consistent histological evidence that autogenous and demineralized allogeneic bone grafts support the formation of new attachment. Limited data also suggest that xenogenic bone grafts can support the formation of a new attachment apparatus. In contrast, essentially all available data indicate that alloplastic grafts support periodontal repair rather than regeneration. The results of this systematic review indicate that bone replacement grafts provide demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone. Ann Periodontol 2003;8:227‐265.