Four-year treatment continuation rates of osteoporosis drugs with different dosing intervals throughout Japan.

INTRODUCTION: There are approximately 13 million patients with osteoporosis in Japan; however, only 20% of them receive treatment. This study compared the 4-year continuation rates of osteoporosis drugs at different dosing intervals across throughout Japan. MATERIALS AND METHODS: Receipt data were analyzed to determine the continuation of osteoporosis medication in patients who began treatment at 210 hospitals throughout Japan between October 2016 and September 2017. Continuation rates were compared using Kaplan-Meier curves and log-rank tests. RESULTS: The 4-year continuation rates of daily, weekly, monthly, semi-annual, and yearly medications nationwide were 8.6%, 16.5%, 13.5%, 31.0%, and 26.0%, respectively. The 4-year continuation rates for semi-annual and yearly drugs were significantly higher than daily, weekly, monthly drugs. CONCLUSION: Throughout Japan, the 4-year treatment continuation rates of daily, weekly, monthly, semi-annual, and yearly osteoporosis drugs all decreased over time. However, the continuation rates of semi-annual and yearly drugs in the fourth year were significantly higher than those for the other dosing regimens. Therefore, injectable drugs with dosing intervals ≥6 months may improve continuation rates of osteoporosis drugs. Geriatr Gerontol Int 2023; 23: 665-670.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.

BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Zoledronic acid significantly enhances radiation­induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling.

Zoledronic acid (ZOL), a third-generation bisphosphonate, inhibits bone resorption, as well as exhibiting direct antitumor activity. To date, however, the combined effects of ZOL and ionizing radiation (IR) have not been assessed in patients with soft tissue sarcoma. We have, therefore, assessed the combined effects of ZOL and IR in fibrosarcoma cells. HT1080 fibrosarcoma cells were treated with ZOL and/or IR, together or sequentially and the antitumor effects were assessed. We found that ZOL significantly enhanced IR-induced apoptosis, especially when cells were treated with ZOL followed by IR. We, therefore, assessed the detailed mechanism of sequential treatment with ZOL and IR. Cells in G2 and M phases, the most radiosensitive phases of the cell cycle, were not increased by low concentrations of ZOL. However, the levels of expression of Akt, ERK1/2 and NF-κB proteins, all of which are related to radioadaptive resistance, were increased within a short time after irradiation with 3 Gy, and this expression was inhibited by a low concentration of ZOL, which blocked the prenylation of small GTPases. This sequential treatment also increased the generation of reactive oxygen species (ROS). These results suggest that the combination of ZOL with IR may be beneficial in treating patients with soft tissue sarcoma.

Chondrosarcoma from the sternum: reconstruction with titanium mesh and a transverse rectus abdominis myocutaneous flap after subtotal sternal excision.

BACKGROUND: Chondrosarcoma arising from the sternum is extremely rare and is often untreatable. Removal of the sternum for malignant tumor results in large defects in bone and soft tissue, causing deformity and paradoxical movement of the chest wall and making subsequent repair of the thorax very important. We report a very rare patient with a chondrosarcoma of the sternum who underwent case chest wall resection, followed by reconstruction using a titanium mesh covered with a transverse rectus abdominis myocutaneous (TRAM) flap. CASE REPORT: A 63-year-old man was referred to our hospital with progressively enlarged swelling of his anterior chest wall. Physical examination showed a 2.5×2.0 cm mass fixed to the sternum, which was diagnosed as a chondrosarcoma based on clinical findings, imaging characteristics and incision biopsy results. The patient underwent a subtotal sternal and chest wall resection to remove the tumor, followed by reconstruction with a titanium mesh and a TRAM flap. There were no complications associated with surgery. CONCLUSIONS: We report an extremely rare case of a patient who underwent subtotal sternal resection, followed by reconstruction, for a large chondrosarcoma. The elasticity and rigidity provided by the titanium mesh and the complete coverage of the surgical wound by a TRAM flap suggest that these procedures may be useful in reconstructing large defects in the chest wall.

Combined effects of bisphosphonate and radiation on osteosarcoma cells.

UNLABELLED: Antitumour effects of third-generation bisphosphonates (BPs), such as zoledronic acid (ZOL), and the combined effects of ZOL with other anticancer agents against osteosarcoma cells have been reported previously. The aim of this study was to identify further combined antitumour effects using BPs and radiation in osteosarcoma cell lines. MATERIALS AND METHODS: Cell proliferation, cell cycle analysis, and nuclear morphology were examined in each osteosarcoma cell line divided into three groups (ZOL alone, radiation alone and the ZOL/radiation combination). RESULTS: Combined therapy (low-concentration ZOL and low-dose radiation) had significant growth inhibitory effects compared to the use of ZOL or radiation individually. Flow cytometric analysis revealed an increase in cells in the sub-G(1) phase by combined treatment, and apoptotic cells were also observed. CONCLUSION: These findings suggest that combination therapy using BPs and radiation may be a promising therapy for osteosarcoma, producing fewer side effects and complications in the near future.

Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents.

Third-generation bisphosphonates are known to inhibit bone resorption and also appear to exhibit direct anti-tumour activity. We previously reported that third-generation bisphosphonates such as zoledronic acid (ZOL) have a direct antitumour effect, and synergistically augment the effects of antitumor agents in osteosarcoma cells. There has been no report on the antitumor effect of ZOL against soft tissue sarcoma. The aim of this study was to evaluate the antitumor effect of this drug on a human fibrosarcoma cell line, in terms of proliferation and apoptosis, and, moreover, to evaluate the combined effects of ZOL with other antitumor drugs against the human fibrosarcoma cell line. HT1080 cells were treated with ZOL at various concentrations up to 10 microM, and then cell proliferation, cell cycle, nuclear morphology, and Western blot analyses were performed to study the antitumor effects of ZOL alone, and, moreover, HT1080 cells were treated with ZOL and other anticancer drugs such as paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, cisplatin, or methotrexate to investigate the combined effects using proliferation and cell cycle analyses. We found that ZOL strongly inhibited in vitro proliferation, arrested the cell cycle between S and G2/M phases, and induced the apoptosis of human fibrosarcoma cells. Moreover, ZOL augmented the effect of antitumor agents when administered concurrently with paclitaxel, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, and cisplatin in human fibrosarcoma cells. The treatment of fibrosarcoma with ordinary antitumor drugs is not fully effective. These findings suggest that ZOL directly affects the proliferation and survival of fibrosarcoma cells, and that the combined administration of ZOL with other antitumor agents may improve the efficacy of fibrosarcoma treatment. These results support the possibility that their combined use could be beneficial in the treatment of patients not only with various types of cancer or osteosarcoma, but also with soft tissue sarcoma.

Characteristic appearance of large subcutaneous gouty tophi in magnetic resonance imaging.

The development of multiple large tophi in patients with gout is rare. We report magnetic resonance (MR) and histological features of large subcutaneous tophi in a 32-year-old male patient with no known arthritis. His subcutaneous lesions were confused with a neoplastic process, evaluated by MR imaging, and surgically excised after biopsy. The honeycomb-like appearance on the gadolinium-enhanced images may reflect the characteristic multilobular structure of the tophi composed of avascular urate deposits and surrounding vascularized granulation tissue.