Examination of Risk Factors and Expression Patterns of Atypical Femoral Fractures Using the Japanese Adverse Drug Event Report Database: A Retrospective Pharmacovigilance Study.

Atypical femoral fracture (AFF) is a rare complication related to the use of bisphosphonates (BPs). Herein, we analyzed the risk factors and onset patterns of AFF using the Japanese Adverse Drug Event Report database and reported the findings. First, the independent risk factors for AFF were gender (female), high body mass index, and medical history of osteoporosis, arthritis, and systemic lupus erythematosus (SLE). Drug-related risk factors for AFF included BPs (i.e., alendronic acid, ibandronic acid, etidronic acid, zoledronic acid, minodronic acid, risedronic acid), denosumab, prednisolone, lansoprazole, rabeprazole, exemestane, letrozole, eldecalcitol, and menatetrenone. Therefore, it appears that AFF is influenced by a combination of patient backgrounds and drugs, and that the risk of developing AFF is particularly high in patients with fragile bones (e.g., osteoporosis, arthritis, and SLE). Second, in the analysis of AFF onset patterns, the onset of AFF from BPs and denosumab took a long time (>1 year) to develop. Analysis using a Weibull distribution showed wear-out failure-type AFF onset for BPs and denosumab, and both osteoporosis and cancer patients with long-term administration of these drugs showed a tendency to have an increased risk of onset. AFF developed earlier in osteoporosis patients with long-term administration of BPs and denosumab than in cancer patients.

Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database.

Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms.

[Psoriasis and Psoriatic Arthritis Induced by Nivolumab in a Patient with Advanced Non-Small-Cell Lung Cancer].

BACKGROUND: Immune checkpoint-blocking antibodies may induce specific side effects known as immune-relatedad verse events. CASE PRESENTATION: A 66-year-oldman without any history of autoimmune disease was referredto our hospital for treatment of lung cancer in the right upper lobe. The tumor was diagnosed as Stage III A non-small-cell lung cancer by using bronchoscopic biopsy, computedtomography, andFDG -PET. After a single course of cisplatin andpemetrexed , the tumor size increasedremarkably andthe regimen was changedto nivolumab(3mg/kg every 2 weeks). Psoriasis andpsoriatic arthritis were observed after 4 courses of nivolumab. Nivolumab treatment continued, and the oral administration of predni- solone(20mg/day)couldimprove psoriasis andpsoriatic arthritis. However, the lung cancer showedprogressive disease after the 11th course of nivolumab. CONCLUSION: Psoriasis andpsoriatic arthritis were inducedby nivolumab in the patient without any history of autoimmune disease. It is unclear how prednisolone affected nivolumab for the treatment of lung cancer.

Bone resorption and inflammatory inhibition efficacy of intermittent cyclical etidronate therapy in rheumatoid arthritis.

OBJECTIVE: Osteoclast activation or cartilage and bone destruction are developed in patients with rheumatoid arthritis (RA). The efficacy of etidronate with respect to osteoporosis, inhibition of bone resorption and destruction, and antiinflammation in RA was examined for 72 weeks. METHODS: Sixty-three patients with RA (56 women, 7 men) were divided into a group that received intermittent cyclical etidronate therapy (ICET) (31 patients) and a non-ICET group (32 patients). Over a 72 week followup period, the urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), bone mineral density (BMD), Larsen damage score, Lansbury activity index, and concentrations of serum C-reactive protein (CRP) and serum interleukin 6 (IL-6) of the 2 groups were compared. RESULTS: In the non-ICET group, a significant decrease in BMD and a significant increase in the Larsen damage score were observed. In the ICET group, the level of DPD started to decrease 12 weeks after etidronate administration and progression of the Larsen damage score was significantly inhibited. IL-6 concentration was significantly decreased 72 weeks after etidronate administration. Concentrations of BAP and CRP and the Lansbury activity index were not significantly different between the ICET and the non-ICET groups. A significant correlation between the IL-6 and DPD concentrations was observed. CONCLUSION: Etidronate was effective at inhibiting bone resorption and destruction in study patients with RA, while not increasing BAP concentrations; and a correlation was observed between the concentration of DPD and IL-6, indicating the antiinflammatory effect of etidronate.