Resumen de Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy
Background: Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies.
Methods: Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting.
Results: Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition.
Conclusion: Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss.
Nearly one of four females and one of eight males aged >50 years are diagnosed with osteoporosis in the United States.1,2 Patients with osteoporosis are typically treated with either bisphosphonate or teriparatide (recombinant human parathyroid hormone [1-34]) therapy. Bisphosphonates are antiresorptives widely used for the management of osteoporosis. More than 150 million prescriptions were written for oral bisphosphonates from 2005 to 2009.3 Conversely, teriparatide, a recombinant human parathyroid hormone (PTH), is a bone anabolic agent used for the treatment of osteoporosis. More than 1 million patients around the world have received teriparatide therapy since 2002.4 Hence, a large elderly population is currently on either bisphosphonate or teriparatide therapy for osteoporosis. Because tooth extractions are common dental procedures in the elderly,5,6 more patients on bisphosphonate or teriparatide therapy are likely to receive tooth extractions and subsequent implant therapy. Therefore, it is crucial for dentists to understand the effect of these therapies on tooth-extraction wound healing to establish better informed consent and postextraction care. Currently, how these drugs influence tooth-extraction wound healing is not clearly defined.
Tooth extractions cause tissue injuries, such as mechanical damage in bony socket walls and soft-tissue lacerations.7 Extraction wounds are typically left exposed to the oral cavity in which many microorganisms reside. Accordingly, intense inflammatory responses occur after tooth extractions.8 Mechanical damage-induced osteocyte death in bony socket walls manifests as necrotic bone that prompts osteoclastic bone resorption for repair. If this process does not occur, necrotic bone is retained and the healing is incomplete. In rats, osteoclasts emerge in the crestal portion of socket walls to resorb damaged bone at 2 days after extractions, resulting in a reduction of inflammatory responses.9 The resolution of inflammation is indeed necessary to advance wound healing and subsequent bone formation. In a previous study in which osteopetrotic rats received tooth extractions, more than one third of the rats developed infections in tooth-extraction wounds and, even in non-infected extraction wounds, bone fill was considerably compromised compared with control rats.10 Although mutant rats were used in the study, the findings suggest that osteoclastic bone resorption plays a pivotal role during healing of tooth-extraction sockets.
Bisphosphonates suppress bone remodeling and resorption by targeting osteoclasts.11 Because osteoclastic resorption of damaged bone is an essential step in tooth-extraction socket healing, it is theorized that bisphosphonate therapy would alter the normal osseous healing process in tooth-extraction sockets. However, the incidence of healing complications, such as infection and osteonecrosis of the jaw (ONJ) after tooth extractions among patients on oral bisphosphonates is low.12 In the case of ONJ, the incidence is estimated at �0.02%.13 Therefore, the majority of tooth-extraction wounds heal successfully and uneventfully in patients on oral bisphosphonates, although osteoclasts are suppressed in these patients. Teriparatide (PTH) therapy increases bone mass by promoting bone remodeling in favor of bone formation versus resorption.14 The bone anabolic effect of PTH therapy appears to be enhanced when applied to osseous tissues in which bone metabolism is active, such as fracture sites15 and rapidly growing bones.16 In the craniofacial region, PTH therapy improves the outcome of periodontal surgeries17 and grafting procedures in rat tooth-extraction sockets.18 Because bisphosphonate therapy suppresses and PTH therapy enhances bone remodeling, the healing pattern of tooth-extraction sockets would be distinct between hosts on bisphosphonate or PTH therapy.
In the present study, the effect of bisphosphonate and PTH therapies on tooth-extraction wound healing is investigated. The objectives are as follows: 1) to characterize, contrast, and compare how bisphosphonate and PTH therapies affect the soft-tissue healing process; and 2) to determine the advantages and disadvantages of each therapy on tooth-extraction wound healing.
