Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

Yu, Youcheng; Lieu, Shirley; Hu, Diane; Miclau, Theodore; Colnot, Céline

doi:10.1371/journal.pone.0031771

Cited by 41 publications

(25 citation statements)

References 48 publications

(62 reference statements)

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“…Regarding the potency of BPs, it is known that ZA is one of the most potent BP in clinical use [14]. Interestingly, in our study three patients receiving this drug developed uncomplicated BRONJ.…”

Section: Discussionsupporting

confidence: 48%

Bisphosphonate-Related Osteonecrosis of the Jaws and Its Array of Manifestations

Rabelo

Assunção

Chavassieux

et al. 2014

J. Maxillofac. Oral Surg.

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Purpose Bisphosphonate (BP) therapy in the treatment of bone diseases and malignancy may induce a major side effect known as bisphosphonate-related osteonecrosis of the jaws (BRONJ). A particular view of this condition is reported in this case series investigating eight patients. The aim of the study was to evaluate the BRONJ lesions concerning their aspects and progression. Also, identify if it is possible to predict the degree of severity in these cases. Methods Patients were evaluated by their condition and systemic health. The lesions were evaluated in clinical and radiographic aspects. The patients were followed-up for 2 years. Results The patients presented with specific peculiarities, and the BRONJ lesions varied in several characteristics. The BRONJ lesions ranged from simple to severe conditions, and the complicated cases presented with major pain, swelling, secondary infection and an extensive necrotic area, classified with high grade of severity. Conclusions The patients presented here confirm the existence of a relation between multiple features and BRONJ and to understand the whole process of aggravation, all systemic and local information have to be taken into account, together with all data related to the BP utilized. Regardless of the low incidence of this side effect in relation to osteoporosis treatment, in some cases, the BRONJ may become a severe condition and compromise the patient's quality of life.

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Section: Discussionsupporting

confidence: 48%

Bisphosphonate-Related Osteonecrosis of the Jaws and Its Array of Manifestations

Rabelo

Assunção

Chavassieux

et al. 2014

J. Maxillofac. Oral Surg.

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“…The site-specific effects of BPs on osteocytes observed in our study could be explained by some differences in the biology of jaw vs peripheral osteoblasts, which have various embryonic origins: in the long bones the osteoblast lineage derives from the trunk lateral plate mesoderm, whereas in the mandible it derives from the paraxial mesoderm [59]. It could also be explained by the different remodeling rate between these skeletal sites, which is higher in the jaw [60], potentially facilitating the accumulation of BPs in the bone matrix [61], [62]. However, after a single infusion of Zol in dogs, drug concentration in jaw and teeth was not higher than in tibia and actually lower than in pelvis or vertebrae [63].…”

Section: Discussionmentioning

confidence: 63%

Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

et al. 2013

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Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 µg/kg/month) and Zol 1W (100 µg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn+/+ and Postn−/− (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn−/−. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn−/− and Postn+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn−/− vs Postn+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn−/− and Postn+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn−/−, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn−/− mice, zoledronate is not sufficient to induce bone necrosis.

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“…This effect was more pronounced in mandible fracture healing than tibia fracture healing in their study [20]. It must be note though that this is in stark contrast to studies in rabbits, in which use of zoledronic acid was observed to accelerate mandible fracture healing.…”

Section: Resultsmentioning

confidence: 74%

How do bisphosphonates affect fracture healing?

Kates

Ackert‐Bicknell

2016

Injury

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Bisphosphonates (BPs) have been in use for many years for the treatment of osteoporosis, multiple myeloma, Paget's disease, as well as a variety of other diseases in which there is reduced bone mineral density. Given that bisphosphonates inhibit bone resorption, an important stage of fracture healing; this class of compounds has been widely studied in preclinical models regarding their influence on fracture healing. In animal models, bisphosphonate treatment is associated with a larger fracture callus, coincident with a delay in remodeling from primary woven bone to lamellar bone, but there is no delay in formation of the fracture callus. In humans, de novo use of bisphosphonate therapy after fracture does not appear to have a significant effect on fracture healing. Rarely, patients with long term use of Bisphosphonates may develop an atypical fracture and delay in fracture healing has been observed. In summary, bisphosphonates appear safe for use in the setting of acute fracture management in the upper and lower extremity in humans. While much remains unknown about the effects on healing of long-term bisphosphonates, use prior to “typical” fracture, in the special case of atypical fracture, evidence suggests that bisphosphonates negatively influence healing.

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Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

Cited by 41 publications

References 48 publications

Bisphosphonate-Related Osteonecrosis of the Jaws and Its Array of Manifestations

Bisphosphonate-Related Osteonecrosis of the Jaws and Its Array of Manifestations

Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

How do bisphosphonates affect fracture healing?

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