Low-dose methotrexate in rheumatoid arthritis: a potential risk factor for bisphosphonate-induced osteonecrosis of the jaw

Abstract

Bisphosphonate-induced osteonecrosis of the jaw [BIONJ] is a relatively new pathological condition which was first described in the year 2003. The prevalence of BIONJ in patients on oral formulations is around 0.05% within the first 3 years and increases up to 0.2% after 4 years of consumption. Proven systemic risk factors like anemia, uncontrolled diabetes, corticosteroid therapy, and chemotherapy in neoplastic diseases [e.g., high doses of methotrexate up to 30 mg daily] significantly increase the chances of acquiring BIONJ. We present three patients with osteoporosis and rheumatoid arthritis [RA] who consumed oral bisphosphonates [alendronate] for less than 1 year and developed BIONJ within 2 to 5 months of undergoing a traumatic dental procedure. The patients also gave a history of consuming low doses of methotrexate [disease-modifying anti-rheumatic drugs] up to 20 mg weekly for 4 to 10 years. No history of steroid consumption was given by any of the patients. This case series highlights the possibility of rheumatoid arthritis and low-dose methotrexate being potential risk factors for BIONJ. This may be on account of the synergistic effect of methotrexate and bisphosphonates and the pro-inflammatory state created by RA which increased the risk of acquiring BIONJ.

Factors Influencing Severity of Medication-Related Osteonecrosis of the Jaw: A Retrospective Study

“…Therefore, when administered in combination with bisphosphonates, there is increased susceptibility for MRONJ. [20][21][22][23][24] It should also be noted that the indications for antiresorptive or antiangiogenic therapy (therapeutic or prophylactic) are similar to those for chemotherapy. Thus, patients with aggressive primary disease are likely to receive chemotherapy in combination with antiresorptive or antiangiogenic therapy.…”

Medication‐related osteonecrosis of the jaw: Analysing the range of implicated drugs from the Australian database of adverse event notifications

“…It has been reported to inhibit bone formation and is associated with increased bone resorption by inhibiting osteoblast proliferation and affecting osteoclast density 39 . Additionally, by suppression of the bone marrow and causing immunosuppression, there are several plausible mechanisms by which methotrexate can be associated with MRONJ 45 …”

“…39 Additionally, by suppression of the bone marrow and causing immunosuppression, there are several plausible mechanisms by which methotrexate can be associated with MRONJ. 45 Teriparatide, a human parathyroid hormone analogue, was listed in the DAEN as a suspected causative agent in 2 cases, with no other drugs listed. While this drug may have contributed to MRONJ, it is not likely to be because its mechanism of action is anabolic and is used in patients with severe osteoporosis, 46 the latter of which may predispose to ONJ and such patients are likely to have been treated…”

Arthritis and dentistry

“…There are case reports of patients suffering from osteonecrosis of the jaw following tooth extraction where both methotrexate and low dose bisphosphonates were being taken. 31 Therefore, this suggests that methotrexate may act as a risk factor for bisphosphonate related osteonecrosis of the jaw. 31 Biological therapies Biological therapies, also known as biologics, are a type of DMARD, however there is benefit in discussing these separately as they are a newer body of drugs with increasing use and importance.…”

“…31 Therefore, this suggests that methotrexate may act as a risk factor for bisphosphonate related osteonecrosis of the jaw. 31 Biological therapies Biological therapies, also known as biologics, are a type of DMARD, however there is benefit in discussing these separately as they are a newer body of drugs with increasing use and importance. These drugs are used to treat IA and are commonly prescribed after failure of conventional DMARDs.…”