Short-term teriparatide therapy as an adjunctive modality for bisphosphonate-related osteonecrosis of the jaws

“…5 Although development of osteosarcoma was not reported in humans, there is no longterm information, thus TP treatment for more than 2 years is not recommended. 37 In the previously reported case reports, TP was injected for 1-6 months in BRONJ treatment and is considered to be a short-term treatment. 37 TP, which is indicated in osteoporosis prevention and treatment, is also indicated in osteoporotic BRONJ patients.…”

Section: Discussionmentioning

confidence: 99%

“…37 In the previously reported case reports, TP was injected for 1-6 months in BRONJ treatment and is considered to be a short-term treatment. 37 TP, which is indicated in osteoporosis prevention and treatment, is also indicated in osteoporotic BRONJ patients. Although TP is contraindicated in patients who have malignant bone diseases and developed BRONJ, 28 studies on the suitability of short-term TP therapy in these patients are needed.…”

Section: Discussionmentioning

confidence: 99%

Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model

Ersan¹,

Ruijven²,

Bronckers³

et al. 2014

Dentomaxillofacial Radiology

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Objectives: The objectives of this study were to establish a bisphosphonate-related osteonecrosis of the jaw (BRONJ) rat model and to analyse the effects of teriparatide (TP) on this model. Methods: Sprague-Dawley rats were divided into three groups: I-zoledronic acid (ZA, n 5 10); II-ZA and teriparatide (ZA 1 TP, n 5 10); III-control (n 5 10). Osteonecrosis was induced by administering zoledronic acid to groups ZA and ZA 1 TP. A week after the injections, rats underwent extraction of the first left mandibular molar. Following a four week period, TP was administered to the ZA 1 TP group for 28 days. Upon killing, extraction sockets were examined clinically, radiologically and histopathologically. Results: Clinical examination revealed necrotic bone exposure in none of the animals. MicroCT (mCT) examination showed that bone mineral density of the newly formed bone in the extraction socket was lower in the ZA group than in the ZA 1 TP group (p , 0.05). Histopathological examination revealed that only the ZA and ZA 1 TP groups developed osteonecrosis, and the osteonecrotic bone area in the ZA group was larger than that in the ZA 1 TP group (p , 0.05). Tartrate-resistant acid phosphatase (TRAcP) enzyme histochemistry revealed that the number of detached and large osteoclasts were higher in the ZA group than in other groups, whereas the number of apoptotic osteoclasts in both ZA and ZA 1 TP groups were higher than in the control group (p , 0.05). Conclusions: Our data indicate that bisphosphonate-related osteonecrosis of the jaw model used in the present study is an attractive model to investigate treatment modalities and that TP might be an effective treatment in BRONJ.

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“…Bisphosphonates exert their anti-resorptive activity by suppression of osteoclasts. A few clinical cases have reported the successful off-label use of teriparatide for treating ONJ (Harper and Fung, 2007;Lau and Adachi, 2009;Cheung and Seeman, 2010;Narongroeknawin et al , 2010;Tsai et al ., 2010;Lee et al , 2011;Kwon et al , 2012;Narvaez et al , 2012). Teriparatide increases bone remodeling and has been reported to reduce microdamage accumulation in the bone, a possible etiology of ONJ.…”

Section: Dental Implant and Implant-related Bone Augmentation Proceduresmentioning

confidence: 99%

“…Animal models with/without induced osteoporosis and gene ablation models support the impact of PTH on bone development and remodeling in the craniofacial region, thus providing a sound rationale for the use of PTH for applications in oral and maxillofacial bone regeneration (Kawane et al, 2002;Rowshan et al, 2010;Valderrama et al, 2010). Preliminary clinical studies have shown promising results with teriparatide for periodontal regeneration and the treatment of osteonecrosis of the jaw related to the use of bone antiresorptive drugs (Tsai et al, 2010;Lee et al, 2011;Kwon et al, 2012). This review will update research on the impact of PTH in the craniofacial skeletal, regeneration applications, and future prospects for clinical benefits of PTH therapy.…”

Section: Introduction Tmentioning

confidence: 99%

Parathyroid Hormone Applications in the Craniofacial Skeleton

Chan

McCauley

2012

J Dent Res

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Parathyroid hormone (PTH) is known for its ability to ‘build’ bone, with research in this area centered on its use as an osteoporosis therapeutic. Recent interest has developed regarding its potential for regenerative applications such as fracture healing and osseous defects of the oral cavity. Many years of investigation using murine gene-targeted models substantiate a role for signaling at the PTH/PTH-related protein (PTHrP) receptor (PPR) in intramembranous bone formation in the craniofacial region as well as in tooth development. Pre-clinical studies clearly support a positive role of intermittent PTH administration in craniofacial bones and in fracture healing and implant integration. A few human clinical studies have shown favorable responses with teriparatide (the biologically active fragment of PTH) administration. Favorable outcomes have emerged with teriparatide administration in patients with osteonecrosis of the jaw (ONJ). New delivery strategies are in development to optimize targeted application of PTH and to help maximize local approaches. The promising host-modulating potential of PTH requires more information to further its effectiveness for craniofacial regeneration and osseous wound-healing, including a better delineation of cellular targets, temporal effects of PTH action, and improved approaches for local/targeted delivery of PTH.

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Short-term teriparatide therapy as an adjunctive modality for bisphosphonate-related osteonecrosis of the jaws

Abstract: In terms of the multifactorial etiology of BRONJ, bone formation suppression was noticed in the patients. Based upon this finding, the short-term use of teriparatide might be beneficial to the resolution of BRONJ lesions by improving suppressed bone remodeling.

Cited by 57 publications

References 20 publications

Efficacy and safety of currently marketed anti-osteoporosis medications

Efficacy and safety of currently marketed anti-osteoporosis medications

Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model

Parathyroid Hormone Applications in the Craniofacial Skeleton

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