Objective: Clinical trials are designed to clarify the dose-dependency of drugs.  However, the dose-dependency of adverse drug reactions (ADR), especially in the subtherapeutic range, often remains unclear.  Whether decreasing a drug’s dose would reduce the risk of ADR is of interest to both clinicians and regulators.  This study aimed to clarify the dose-dependency of ADR during subtherapeutic exposure to non-steroidal anti-inflammatory drugs, immunosuppressants, β-adrenoceptor antagonists, or corticosteroids.
Methods: Data about the ADR risk profiles and the area under the concentration curve (AUC) values of the examined drugs during their subtherapeutic administration, e.g., after their topical or low-dose oral administration, were collected from the literature and compared with data obtained during the therapeutic administration of the drugs; i.e., at the standard oral dosage.
Results: The drugs that exhibited AUC of ≥20% during their therapeutic administration continued to cause significant systemic ADR during their subtherapeutic administration.  Whilst the drugs that demonstrated AUC of 3-20% during their therapeutic administration continued to cause systemic ADR during their subtherapeutic administration, the ADR tended to be less frequent.
Conclusion: The dose-dependency of ADR can be estimated by comparing the AUC and ADR risk profile data for a drug obtained during its topical, parenteral, or low-dose oral administration with that obtained during its oral administration at the standard dose.  However, some studies have detected high ADR frequencies even during reduced systemic exposure, suggesting that factors affecting the risk of ADR, e.g., patients’ background data, should be carefully matched between the datasets being compared.

Shichimotsukokato is composed of shimotsuto with chotoko, ogi, obaku, and this formula has been frequently used for the treatment of hypertension, eye-fundal hemorrhage and headaches. Here we describe three cases of chronic dermatitis with hypertension and dry skin of legs, which were successfully treated with shichimotsukokato. Case 1 was a 67-year-old man whose chief complaint was pruritus and skin eruption on his chest. He also had dry skin accompanied with pruritus on his legs, and hypertension. Case 2 was a 59-year-old man who had skin eruption accompanied with pruritus on his trunk and extremities. He also showed diastolic hypertension and renal insufficiency due to the side effect of an immunosuppressant. Case 3 was a 64-year-old man who had dry skin with eruption on the upper trunk. Furthermore, his blood pressure fluctuated within the high normal range. After medication with shichimotsukokato, both the hypertension and dermatitis improved in all three cases.
According to these observations, shichimotsukokato may alleviate dermatitis along with dry skin of legs and hypertension, and it may be worth noting that shichimotsukokato is an option for the treatment of skin lesion.

Objectives: To investigate effects of romosozumab treatment on disease activity and bone mineral density (BMD) in patients with rheumatoid arthritis (RA) and severe osteoporosis in comparison with effects of denosumab treatment. Methods: A total of 50 women were enrolled in this study. The subjects were randomized equally into 2 groups: the romosozumab group or the denosumab group. Disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and BMD at lumbar spine were evaluated. Results: The percent changes (Δ) in the BMD values at 3 and 6 months for the lumbar spine were as follows: romosozumab; 4.9% and 5.2%, denosumab: 2.3% and 3.2%. The ΔBMD for the lumbar spine at 3 months was significantly higher in the romosozumab group than in the denosumab group (P = 0.044). The DAS28-ESR at baseline, 3 and 6 months in the romosozumab group were 2.88, 2.60 (P = 0.427) and 2.58 (P = 0.588), respectively. The change from baseline in DAS28-ESR did not differ significantly between these 2 groups at any time point. Conclusions The present study revealed that romosozumab treatment is more effective than denosumab treatment in increasing BMD of the lumbar spine at 3 months. Furthermore, the present study suggested that romosozumab treatment has no effects on the disease activity of RA in patients with RA and severe osteoporosis for 6 months.

Objectives: To investigate effects of romosozumab treatment on disease activity and bone mineral density (BMD) in patients with rheumatoid arthritis (RA) and severe osteoporosis in comparison with effects of denosumab treatment. Methods: A total of 50 women were enrolled in this study. The subjects were randomized equally into 2 groups: the romosozumab group or the denosumab group. Disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and BMD at lumbar spine were evaluated. Results: The percent changes (Δ) in the BMD values at 3 and 6 months for the lumbar spine were as follows: romosozumab; 4.9% and 5.2%, denosumab: 2.3% and 3.2%. The ΔBMD for the lumbar spine at 3 months was significantly higher in the romosozumab group than in the denosumab group (P = 0.044). The DAS28-ESR at baseline, 3 and 6 months in the romosozumab group were 2.88, 2.60 (P = 0.427) and 2.58 (P = 0.588), respectively. The change from baseline in DAS28-ESR did not differ significantly between these 2 groups at any time point. Conclusions The present study revealed that romosozumab treatment is more effective than denosumab treatment in increasing BMD of the lumbar spine at 3 months. Furthermore, the present study suggested that romosozumab treatment has no effects on the disease activity of RA in patients with RA and severe osteoporosis for 6 months.

Objectives: This study aims to examine the 2-year outcomes of zoledronic acid (ZOL) with or without eldecalcitol (ELD) on bone mineral density (BMD) and fracture in Japanese patients with osteoporosis. Methods: The subjects were 98 patients who were randomly (1:1) assigned to treatment with ZOL combined with ELD (ZOL + ELD group; n = 51) and ZOL alone (ZOL group; n = 47). Treatment efficacy was examined based on a comparison of changes in BMD from baseline (DBMD) in the lumbar spine, total hip, and femoral neck in the 2 groups. Results: The percent change from baseline in BMD values for the lumbar spine, total hip, and femoral neck at 24 months were 10.8% ± 6.1%, 6.0% ± 6.6%, and 5.1% ± 5.1%, respectively, in the ZOL + ELD group, and 7.7% ± 6.2%, 5.1% ± 5.6%, and 2.9% ± 8.3%, respectively, in the ZOL group. The percent change from baseline BMD for the lumbar spine at 24 months differed significantly between the 2 groups. Conclusions The effect of a combination of ZOL + ELD on BMD for 24 months was more favorable than that of ZOL alone. This drug combination is promising for the treatment of drug-naïve Japanese patients with primary osteoporosis.

Background: The long-term effects of daily teriparatide (D-TPTD) and twice-weekly TPTD (W-TPTD) injections are compared among postmenopausal women with severe osteoporosis. Methods: A total of 102 patients were enrolled and randomly allocated into two groups for the administration of either D-TPTD or W-TPTD. Treatment efficacy was measured as the percentage change in bone mineral density (ΔBMD) from baseline in the lumbar spine, total hip, and femoral neck. The findings were compared between the two groups. Results: At 24 months after treatment, the persistence rates and medication possession ratios in the D-TPTD and W-TPTD groups were 68.6% and 56.9%, and 87.8% and 92.0%, respectively. The ΔBMD in the lumbar spine, total hip, and femoral neck were 15.6%±10.2%, 5.3%± 6.3%, and 5.5%±6.2%, respectively, in the D-TPTD group; and 9.5%±7.9%, 2.3%±6.2%, and 3.1%±7.4%, respectively, in the W-TPTD group following 24 months of treatment. The ΔBMD of the lumbar spine (p=0.008) at 24 months and total hip (p=0.024) at 18 months differed significantly between the two groups. Conclusions D-TPTD administration resulted in a significantly higher BMD in the lumbar spine and total hip, supporting this therapeutic regimen for postmenopausal women with severe osteoporosis.

Purpose: In Japan, the data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers after the booster dose of the coronavirus disease 2019 (COVID-19) vaccine are insufficient. The aim of this study is to evaluate changes in SARS-CoV-2 antibody titers before, 1, 3, and 6 months after the booster dose of the BNT162b2 COVID-19 vaccine among health care workers. Materials and Methods: A total of 268 participants who received the booster dose of the BNT162b2 vaccine were analyzed. SARS-CoV-2 antibody titers were measured before (baseline) and at 1, 3, and 6 months after the booster dose. Factors associated with changes in SARS-CoV-2 antibody titers at 1, 3, and 6 months were analyzed. Cutoff values at baseline were calculated to prevent infection of the omicron variant of COVID-19. Results: The SARS-CoV-2 antibody titers at baseline, and 1, 3, and 6 months were 1,018.3 AU/mL, 21,396.5 AU/mL, 13,704.6 AU/mL, and 8,155.6 AU/mL, respectively. Factors associated with changes in SARS-CoV-2 antibody titers at 1 month were age and SARS-CoV-2 antibody titers at baseline, whereas changes in SARS-CoV-2 antibody titers at 3 and 6 months were associated with the SARS-CoV-2 antibody titers at 1 month. The cutoff values of the SARS-CoV-2 antibody titers at baseline were 515.4 AU/mL and 13,602.7 AU/mL at baseline and 1 month after the booster dose, respectively. Conclusion This study showed that SARS-CoV-2 antibody titers increase rapidly at 1 month after the booster dose of the BNT162b2 vaccine and begin to decrease from 1 to 6 months. Hence, another booster may be needed as soon as possible to prevent infection.

Background: Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and vertebral fractures. This study aimed to investigate factors associated with vertebral fractures and treatment goals to prevent new vertebral fractures in patients with RA. Methods: The database used in this study included outpatient data of RA patients at the authors’ hospital of RA patients taken from 2018 to 2022. The patients underwent annual imaging evaluations to assess parameters, including bone mineral density of the lumbar spine (LS; L2-4), total hip, and femoral neck, as well as vertebral fractures. Vertebral fractures were evaluated using radiographic images of the T8 to L5 vertebrae. Results: The prevalence rates of new vertebral fractures in 2018–2019, 2019–2020, 2020– 2021, and 2021–2022 were 2.0%, 1.3%, 2.3%, and 2.0%, respectively. The presence of existing vertebral fractures was associated with new vertebral fractures (p=0.003; odds ratio, 0.241; 95% confidence interval, 0.093–0.624). The cut-off T-score values for the LS for new vertebral fractures in patients with or without pre-existing vertebral fractures were -0.7 (sensitivity, 40.9%; specificity, 100%) and -1.4 (sensitivity, 69.0%; specificity, 62.5%), respectively. Conclusions The presence of pre-existing vertebral fractures is an independent factor associated with new vertebral fractures. It is important to tailor treatment goals based on the presence or absence of vertebral fractures to effectively prevent new fractures.

Background: Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and vertebral fractures. This study aimed to investigate factors associated with vertebral fractures and treatment goals to prevent new vertebral fractures in patients with RA. Methods: The database used in this study included outpatient data of RA patients at the authors’ hospital of RA patients taken from 2018 to 2022. The patients underwent annual imaging evaluations to assess parameters, including bone mineral density of the lumbar spine (LS; L2-4), total hip, and femoral neck, as well as vertebral fractures. Vertebral fractures were evaluated using radiographic images of the T8 to L5 vertebrae. Results: The prevalence rates of new vertebral fractures in 2018–2019, 2019–2020, 2020– 2021, and 2021–2022 were 2.0%, 1.3%, 2.3%, and 2.0%, respectively. The presence of existing vertebral fractures was associated with new vertebral fractures (p=0.003; odds ratio, 0.241; 95% confidence interval, 0.093–0.624). The cut-off T-score values for the LS for new vertebral fractures in patients with or without pre-existing vertebral fractures were -0.7 (sensitivity, 40.9%; specificity, 100%) and -1.4 (sensitivity, 69.0%; specificity, 62.5%), respectively. Conclusions The presence of pre-existing vertebral fractures is an independent factor associated with new vertebral fractures. It is important to tailor treatment goals based on the presence or absence of vertebral fractures to effectively prevent new fractures.

Background: Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and vertebral fractures. This study aimed to investigate factors associated with vertebral fractures and treatment goals to prevent new vertebral fractures in patients with RA. Methods: The database used in this study included outpatient data of RA patients at the authors’ hospital of RA patients taken from 2018 to 2022. The patients underwent annual imaging evaluations to assess parameters, including bone mineral density of the lumbar spine (LS; L2-4), total hip, and femoral neck, as well as vertebral fractures. Vertebral fractures were evaluated using radiographic images of the T8 to L5 vertebrae. Results: The prevalence rates of new vertebral fractures in 2018–2019, 2019–2020, 2020– 2021, and 2021–2022 were 2.0%, 1.3%, 2.3%, and 2.0%, respectively. The presence of existing vertebral fractures was associated with new vertebral fractures (p=0.003; odds ratio, 0.241; 95% confidence interval, 0.093–0.624). The cut-off T-score values for the LS for new vertebral fractures in patients with or without pre-existing vertebral fractures were -0.7 (sensitivity, 40.9%; specificity, 100%) and -1.4 (sensitivity, 69.0%; specificity, 62.5%), respectively. Conclusions The presence of pre-existing vertebral fractures is an independent factor associated with new vertebral fractures. It is important to tailor treatment goals based on the presence or absence of vertebral fractures to effectively prevent new fractures.