Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing

Abstract

SummaryAdministration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen.IntroductionOsteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. Our objective was to determine the effect of intermittent PTH administration on early osseous healing in the jaw and long bones of rats receiving bisphosphonate and steroid treatment.MethodsOvariectomized rats received the combination therapy of alendronate and dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and tibia. PTH was administered intermittently and healing at 2 weeks post-op was compared between the jaw and tibia by microcomputed tomography and histomorphometric analyses.ResultsALN/DEX treatment was associated with necrotic open wounds in the jaw but had no negative effects on healing and promoted bone fill in tibial defects. PTH therapy prevented the development of necrotic lesions in the jaw and promoted healing of the tibial defects. PTH therapy was associated with the promotion of osteocyte survival in osseous wounds both in the jaw and tibia.ConclusionsWound healing was impaired in the jaw in rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued necrotic lesions. These findings suggest that PTH therapy could be utilized to prevent ONJ from occurring in patients on combination antiresorptive and steroid therapy.

Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study

“…Bashutski et al 33 reported that teriparatide exerted positive effects on healing bone defects in the oral cavity. Teriparatide was reported to be effective in the healing of necrotic wounds in rats administered BPs and steroids by Kuroshima et al 34 In other studies, Kuroshima et al 35 reported that teriparatide promotes healing of the tooth extraction socket. Kuroshima et al 34 in a study associated with BPs and steroids reported that osteoblasts were considerably increased and osteoclasts and necrotic bone were decreased by teriparatide after BP and steroid use.…”

The effect of laser therapy on the expression of osteocalcin and osteopontin after tooth extraction in rats treated with zoledronate and dexamethasone

“…Lopez-Jornet et al found that perioperative antibiotics reduced BRONJ incidence after tooth extractions in rats treated with dexamethasone and pamidronate [38]. Three independent studies demonstrated the preventive role of teriparatide, a synthetic recombinant analogue of parathyroid hormone [18,39,40]. Other authors reported the positive effect of the socket mucoperiosteal coverage and of an atraumatic surgical procedure [41,42].…”

Surgical treatment of bisphosphonate-associated osteonecrosis: Prognostic score and long-term results

“…While in general the focus of osteoprotective therapy to date has been antiresorptive treatment, future perspectives portend an improvement of local bone quality (J€ ager et al, 2010;Yamada et al, 2014) as well as an osteoanabolic strategy using a recombinant fragment of the parathyroid hormone teriparatide (Ohbayashi et al, 2013;Kuroshima et al, 2014).…”