Teriparatide Promotes Bone Healing in Medication-Related Osteonecrosis of the Jaw: A Placebo-Controlled, Randomized Trial

Abstract

<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it. </jats:p></jats:sec>

Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches

“…There is also an opinion that teriparatide shows its efficacy by activating WNT signaling and suppressing sclerostin production [ 133 ]. The osteoanabolic effect of teriparatide was confirmed in the craniofacial area [ 3 , 16 ], and in the field of dentistry, it was also found to promote bone growth and healing in patients with chronic periodontitis [ 137 ]. Due to this tangible osteoanabolic effect, expectations for the application of teriparatide for the management of MRONJ are increasing.…”

“…Since the bone turnover rate of the alveolar bone is more than ten times faster than that of the long bone, it seems to be related to the ability to contain much more bisphosphonates in the alveolar bone compared to the bones in other sites [ 12 ]. Although there are objections that bone turnover is not reduced in osteonecrosis lesions [ 13 ], and active bone resorption occurs due to the presence of osteoclasts in the osteonecrotic areas [ 14 , 15 ], this hypothesis is further strengthened by the favorable results of teriparatide, which stimulates the osteoclast activity [ 3 , 16 ].…”

“…At present, studies on molecular and cellular approaches targeted to hypotheses that are presumed to be the mechanism of MRONJ are being conducted. Among them, teriparatide has recently been proven effective through a randomized controlled trial [ 3 ], showing the possibility as a promising therapeutic agent in the future. Furthermore, bone morphogenetic protein (BMP) and autologous platelet concentrates (APC) are applied in clinical and research environments as adjunctive agents.…”

Cell therapy for medication-related osteonecrosis of the jaw: update on treatment strategies

“…The working hypothesis was that this would counteract the difficulties in reconstructive surgery caused by NBPs. Previous studies have investigated novel approaches for MRONJ treatment, including hyperbaric oxygen therapy (Freiberger et al, 2012), platelet-rich plasma (Adornato et al, 2007;Curi et al, 2011), low-intensity laser irradiation (Favia et al, 2018;Scoletta et al, 2010), parathyroid hormones (Cheung and Seeman, 2010;Sim et al, 2020), bone morphogenetic proteins (Park et al, 2017), plasma rich in growth factors (Mozzati et al, 2012), pentoxifylline and tocopherol (Heifetz- Li et al, 2019), and cell therapy (Tables 2 and 3). Of these, no treatment modality is widely accepted (De Souza Tolentino et al, 2019).…”

“…Of these, no treatment modality is widely accepted (De Souza Tolentino et al, 2019). Sim et al (2020) demonstrated the promising therapeutic effects of teriparatide, which is a parathyroid hormone, against MRONJ in a randomized controlled clinical trial. However, the use of teriparatide in MRONJ patients is challenging, because its administration is difficult in cancer patients, and the duration of administration is limited to 24 months.…”