Calcif Tissue Int (2014) 95:94–96 DOI 10.1007/s00223-014-9858-3

CASE REPORTS

Teriparatide Therapy for Denosumab-Induced Osteonecrosis of the Jaw in a Male Osteoporotic Patient Audrey Neuprez • E. Rompen • J. M. Crielaard Jean-Yves Reginster



Received: 10 March 2014 / Accepted: 1 April 2014 / Published online: 8 May 2014 Ó Springer Science+Business Media New York 2014

Abstract We report the first case of teriparatide adjuvant role in the management of a denosumab-induced osteonecrosis of the jaw in a male subject with idiopathic osteoporosis. Clinical benefits and CT healing were obtained within 2 months of teriparatide initiation and denosumab withdrawal. Increase in bone turnover previously described, when denosumab treatment is removed, might have a synergistic effect to the stimulating effect of teriparatide on bone remodeling to promptly heal osteonecrosis of the jaw.

J.-Y. Reginster received consulting fees or was on paid advisory boards for Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed-Takeda, NPS, IBSAGenevrier, Theramex, UCB, Asahi Kasei, and Endocyte. Lecture fees when speaking at the invitation of a commercial sponsor were received from Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Merckle, Teijin, Teva, Analis, Theramex, Nycomed, NovoNordisk, Ebewee Pharma, Zodiac, Danone, Will Pharma, and Amgen. Grant support from industry was received from Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Roche, Amgen, Lilly, Novartis, GlaxoSmithKline, Servier, Pfizer, Theramex, Danone, Organon, Therabel, Boehringer, Chiltern, and Galapagos. A. Neuprez: Grants were received from Amgen and Servier. E. Rompen and J. M. Crielaard report that they have no conflict of interest. A. Neuprez (&)  J.-Y. Reginster Belgium and Bone and Cartilage Metabolism Unit, Department of Public Health, Epidemiology and Health Economics , University of Lie`ge, CHU, Lie`ge, Belgium e-mail: [email protected] A. Neuprez  J. M. Crielaard  J.-Y. Reginster Motricity Sciences Department, CHU, Lie`ge, Belgium E. Rompen Stomatology Department, CHU, Lie`ge, Belgium

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Keywords Treatment

Denosumab  Osteonecrosis  Teriparatide 

Osteonecrosis of the jaw (ONJ) is a clinical condition that presents as exposed bone in the mandible, maxilla, or both that persists for at least 8 weeks in the absence of previous irradiation or metastases in the jaw. A positive relationship was described between ONJ occurrence and the use of inhibitors of bone resorption in patients with multiple myeloma, metastatic breast cancer, Paget disease, osteoporosis (OP), and other skeletal disorders [1]. We previously reported the development of ONJ in a 58-year-old white man diagnosed with idiopathic predominantly trabecular OP within 4 months of the initiation of an off-label prescription of denosumab for the management of his OP [2]. CT scan of the right mandible revealed an extensive osteolysis with a sequestrum in the medullary cavity surrounded by a periosteal thickening, confirming the ONJ subsequent to a mandibular osteomyelitis [2]. Treatment included antibiotic therapy, removal of necrotic bone, and treatment with a bone anabolic agent (teriparatide [TPD], 20 lg/d subcutaneously) with the maintenance of daily supplementation with calcium and vitamin D. Denosumab was withdrawn at the time of ONJ diagnosis. Oral pain promptly disappeared, and CT of the right mandible performed 65 days after TPD initiation revealed a significant reduction in the size of the necrotic area. After 130 days of TPD treatment (Fig. 1), healing was almost completed. Whereas ONJ was predominantly reported as an adverse event linked to bisphosphonates use [3], cases of ONJ were also described in postmenopausal women receiving denosumab treatment for OP [4]. Our previous report was, however, the first description of ONJ in a male patient treated for idiopathic OP with denosumab [2].

A. Neuprez et al.: Teriparatide Therapy for Osteonecrosis

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Fig. 1 CT scan of the right mandibule showing a significant reduction in the size of the necrotic area and an almost completed healing (after 130 days of teriparatide treatment)

The management of ONJ is considered to be difficult in many cases because it often does not respond to conservative treatment [5]. Peptides from the parathyroid hormone family, including TPD, are used in the management of postmenopausal OP as well as OP in male subjects because their intermittent administration (e.g., through daily subcutaneous injections) results in an increase of the number and activity of osteoblasts, leading to an increase in bone mass and then improvement in skeletal architecture at both the trabecular and cortical skeleton [6]. TPD was suggested to be an effective adjuvant therapy in bisphosphonate-induced ONJ [5, 7], whereas other reports suggested this effect to be inconsistent [8]. Here we report what to our knowledge is the first case of denosumabinduced ONJ healing after the course of subcutaneous TPD. An interesting feature of our case report is the prompt healing of the ONJ cavity after denosumab discontinuation and TPD initiation. One of the proposed mechanisms for ONJ suggests that the disease can be caused by druginduced low bone turnover, which leads to decreased blood flow, bone cells necrosis, and apoptosis [1]. Discontinuation of denosumab in OP patients appears to result in a substantial bone loss and in an increase in bone markers, reflecting a transient increase in bone turnover [9]. This can be a potentially worrisome scenario if one accepts the current paradigm that rapid bone loss and sustained increase in bone turnover are independently associated with increased fracture risk [10]. However, this might also have beneficial effects for ONJ healing, in contrast to the long-term inhibition of bone turnover induced by bisphosphonate, even after treatment withdrawal. The increase in bone turnover that occurs when the drug is removed might have a synergistic effect to TPD to stimulate bone remodeling and help heal ONJ lesions. In conclusion, we report here the first case of TPD’s adjuvant role in the treatment of denosumab-induced ONJ

in a male osteoporotic patient. Although further investigations are needed to better define the role of TPD in the treatment of ONJ, this medication, combined with the removal of denosumab, may provide fast relief in denosumab-induced ONJ. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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Teriparatide therapy for denosumab-induced osteonecrosis of the jaw in a male osteoporotic patient.

We report the first case of teriparatide adjuvant role in the management of a denosumab-induced osteonecrosis of the jaw in a male subject with idiopa...
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