Periodontal regeneration (rhFGF-2 + DBBM): what long-term stability?

The combined use of recombinant human fibroblast growth factor-2 (rhFGF-2) and deproteinized bovine bone mineral (DBBM) currently constitutes a cutting-edge therapeutic approach for the treatment of intrabony defects. While this synergy between a potent biological agent and a mineral matrix is recognized for its favorable and predictable clinical results, scientific perspective on late complications and very long-term biological interactions remains fragmentary.

This clinical case report specifically addresses this lack of data by documenting the extensive follow-up of a 40-year-old female patient suffering from stage III, grade C generalized periodontology. The intervention focused on a one-wall intrabony defect located on the mandibular left first molar (#19), treated with the combination of rhFGF-2 and DBBM.

The objective of this presentation is to evaluate the long-term stability of the regeneration achieved and to highlight the clinical challenges that may arise several years after the surgical procedure. The authors explore the hypothesis that the prolonged persistence of DBBM particles, although volume-stabilising, could induce a specific cellular response — mediated by macrophage or osteoclast lineages — likely to alter the interface between the biomaterial and the adjacent root surface. This long-term follow-up aims to refine our understanding of biomaterial-tissue interactions to secure our future therapeutic choices.

Case report methodology

This case report documents the clinical management and long-term follow-up of a single 40-year-old female patient diagnosed with generalized periodontitis stage III, grade C. The intervention focused specifically on the treatment of a one-wall intrabony defect located on the mandibular left first molar (tooth #19).

The regenerative periodontology therapy protocol was based on the combined use of two biological and biosynthetic agents:

• rhFGF-2: Recombinant human fibroblast growth factor-2.
• DBBM: Deproteinized Bovine Bone Mineral.

Post-operative clinical follow-up was conducted continuously over a total period of 6 years and 2 months, allowing for the identification of different evolutionary phases:

• Initial follow-up (0 to 4 years): Monitoring of healing and stability of periodontal tissues.
• Intermediate evaluation (5 years and 2 months): Detection of a gradual increase in probing depth.
• Final evaluation (6 years and 2 months): Diagnosis of pulpal complications and root lesions.

The analysis methods included the systematic recording of probing depths, clinical examination of pulpal symptoms, as well as radiographic and physical evaluation to identify the agglomeration of DBBM particles and the presence of palpable external root resorption lesions.

Clinical evolution and long-term observations

The post-operative follow-up of this 40-year-old patient, treated for generalized stage III grade C periodontology, revealed a healing dynamic in two distinct phases. The one-wall intrabony defect on tooth #19 (left mandibular first molar) initially responded positively to the combined therapy (rhFGF-2 + DBBM).

Qualitative observations and failure diagnosis

The clinical investigation conducted upon the recurrence of symptoms at 6 years and 2 months identified major structural complications:

• Biomaterial persistence: Presence of an agglomerate of DBBM (Deproteinized Bovine Bone Mineral) particles at the treated site.
• External root resorption (ERR): Evidence of a palpable external root resorption lesion on the adjacent root surface.
• Endodontic involvement: Diagnosis of irreversible pulpal involvement related to the progression of resorption.

The clinical outcome was the extraction of tooth #19, rendered inevitable by the extent of root damage and pulpal involvement, despite an initial period of therapeutic success of 48 months. The authors associate this late resorptive pathology with the prolonged persistence of DBBM particles and a complex cellular response (macrophage/osteoclast lineage) at the root-biomaterial interface.

Analysis of a late failure: when regeneration turns against the root

This clinical case highlights a frustrating reality: a brilliant initial success at 4 years does not guarantee long-term durability. Clinically, the evolution of this 40-year-old patient suggests that the interaction between rhFGF-2 and DBBM can, in rare cases, induce a delayed resorptive pathology. The prolonged persistence of the bone substitute particles and their partial separation seem to have triggered a cellular response (macrophage or osteoclast lineage) deleterious to the adjacent root surface, leading to palpable external root resorption (ERR).

The primary interest of this report lies in the timing of the complication. While the rhFGF-2/DBBM combination is recognized for its favorable results on intrabony defects, the onset of pulpal symptoms and an increase in probing depth after 5 years is atypical. This demonstrates that DBBM remains a material whose prolonged presence can interfere with root homeostasis. The main limitation of this observation is its unique nature (n=1), which does not allow for a statistical quantification of this risk.

Nevertheless, the clinical implication is immediate: the practitioner must maintain constant vigilance. This case proves that an agglomerate of graft particles can become the focus of late inflammation. Beyond immediate surgical success, radiographic and clinical monitoring beyond the 5-year mark is imperative to detect these silent complications before they necessitate extraction.

In concrete terms, for the practitioner:

• Extend vigilance: Maintain rigorous clinical and radiographic follow-up well beyond the usual 2-year mark, as major resorptive complications can occur very late (more than 5 years post-op).
• Monitor biomaterials: In one-wall defects, the prolonged persistence of DBBM and its interaction with rhFGF-2 could induce a deleterious osteoclastic response on the adjacent root surface.
• Inform about the risk: Include the risk of late external root resorption in your informed consent, even if combined regenerative therapy shows excellent initial clinical efficacy.

Technical lexicon of the study

rhFGF-2 (Recombinant human fibroblast growth factor-2): Synthetic growth factor used in regenerative periodontology therapy to stimulate the proliferation of mesenchymal cells and the formation of new supporting tissue.

DBBM (Deproteinized Bovine Bone Mineral): Bone substitute of natural origin (bovine) from which the organic phase has been removed, used as an osteoconductive scaffold to stabilize the clot and maintain space in infra-bony defects.

One-wall infra-osseous defect: Type of periodontal lesion characterized by the loss of three of the four alveolar bone walls surrounding the tooth, representing a major clinical challenge for regeneration due to the low stability of the graft.

External root resorption: Pathological process leading to the loss of cementum and dentin on the external root surface, induced here late by a cellular reaction (macrophages/osteoclasts) in contact with biomaterials.

Stage III grade C periodontitis: Clinical classification describing severe periodontitis with risk of tooth loss (stage III) and rapid progression or severity disproportionate to plaque deposits (grade C).

Osteoclast-lineage cells: Specialized cells in the resorption of mineralized tissues, suspected in this case of being activated by the prolonged persistence or separation of DBBM particles, leading to the degradation of the adjacent root.

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