Chemotherapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer. MATERIALS AND METHODS: This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6 months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. RESULTS: Eighteen women were included in the study (median age: 57 years; range: 55-62 years). At 6 months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01; -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09; -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline. CONCLUSION: Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6 months after chemotherapy.

Incidence and characteristics of aspiration pneumonia in the Nagasaki Prefecture from 2005 to 2019.

BACKGROUND: Aspiration pneumoniae remains a major health concern, particularly in the older population and has poor prognosis; however, the concept itself remains vague worldwide. This study aimed to determine the actual situation and characteristics of aspiration pneumonia from 2005 to 2019 in Nagasaki Prefecture, Japan. METHODS: Cases of aspiration pneumonia that occurred in the Nagasaki Prefecture between 2005 and 2019 were analyzed using emergency transportation records. The number of occurrences and incidence were analyzed according to age, sex, month, day of the week, and recognition time to clarify the actual situation of aspiration pneumonia. RESULTS: The total number of new aspiration pneumonia cases was 8,321, and the mean age of the patients was 83.0 years. Annual incidence per 100,000 population increased from 12.4 in 2005 to 65.1 in 2019, with the most prominent increase in the ≥ 80-year-old stratum. Males (55.1%) were more commonly affected than females (44.9%), and 82.2% of the cases involved patients aged ≥ 70 years. No significant correlations were observed between the incidence of aspiration pneumonia and season, month, or day of the week. Aspiration pneumonia occurred frequently in houses (39.8%) and facilities for elderly individuals (40.8%). At 7 days after admission, 80.9% of patients were still hospitalized and 6.5% had died. CONCLUSIONS: The incidence of aspiration pneumonia with risks of severity and mortality is increasing among elderly individuals. Valid preventive measures are urgently needed based on the findings that the disease occurs in both household and elderly care facility settings, regardless of the season.

Comparison of short-term clinical outcomes between open-wedge high tibial osteotomy and tibial condylar valgus osteotomy.

BACKGROUND: This study aimed to compare radiological features and short-term clinical outcomes between open-wedge high tibial osteotomy (OWHTO) and tibial condylar valgus osteotomy (TCVO), to provide information facilitating decision-making regarding those two procedures. METHODS: Twenty-seven cases involving 30 knees that had undergone OWHTO (HTO group) and eighteen cases involving 19 knees that had undergone TCVO (TCVO group) for medial compartment knee osteoarthritis (OA) were retrospectively evaluated. Patient characteristics, severity of knee OA, lower limb alignment, joint congruity and instability were measured from standing full-length leg and knee radiographs obtained before and 1 year after surgery. Range of motion in the knee joint was measured and Knee Injury and Osteoarthritis Outcome Score (KOOS) was obtained to evaluate clinical results preoperatively and 1 year postoperatively. RESULTS: Mean age was significantly higher in the TCVO group than in the HTO group. Radiological features in the TCVO group included greater frequencies of advanced knee OA, varus lower limb malalignment, higher joint line convergence angle, and varus-valgus joint instability compared to the HTO group before surgery. However, alignment of the lower limb and joint instability improved to comparable levels after surgery in both groups. Maximum flexion angles were significantly lower in the TCVO group than in the HTO group both pre- and postoperatively. Mean values in all KOOS subscales recovered similarly after surgery in both groups, although postoperative scores on three subscales (Symptom, Pain, and ADL) were lower in the TCVO group (Symptom: HTO, 79.0; TCVO, 67.5; Pain: HTO, 80.5; TCVO, 71.1; ADL: HTO, 86.9; TCVO, 78.0). CONCLUSIONS: Both osteotomy procedures improved short-term clinical outcomes postoperatively. TCVO appears preferable in cases of advanced knee OA with incongruity and high varus-valgus joint instability. An appropriate choice of osteotomy procedure is important to obtain favorable clinical outcomes.

Association of denosumab with serum cytokines, chemokines, and bone-related factors in patients with rheumatoid arthritis: A post hoc analysis of a multicentre, open-label, randomised, parallel-group study.

OBJECTIVES: To clarify changes in serum cytokines, chemokines, and bone-related factors during denosumab treatment in rheumatoid arthritis (RA) patients. METHODS: This was a post hoc analysis of a multicentre, open-label, randomised, parallel-group study. Patients were randomly assigned to continue treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) plus receive treatment with denosumab (csDMARDs plus denosumab group) or to continue treatment with csDMARD therapy alone for 12 months. Serum biomarker levels were measured at baseline and at 6 and 12 months. RESULTS: Baseline and 6-month data from the csDMARDs plus denosumab (n = 22) and csDMARD therapy alone (n = 22) groups were analysed. Statistically significant changes from baseline were seen: Dickkopf-related protein 1 decreased at 6 and 12 months (both groups); osteopontin decreased at 6 months in the csDMARDs plus denosumab group; osteopontin and soluble CD40 ligand increased at 6 and 12 months in the csDMARD therapy alone group; osteocalcin decreased at 6 and 12 months, epidermal growth factor decreased at 12 months, and macrophage-derived chemokine decreased at 6 months in the csDMARDs plus denosumab group; and interferon gamma-induced protein-10 increased at 12 months in the csDMARD therapy alone group. CONCLUSIONS: Denosumab may inhibit bone destruction by suppressing bone-related factors/chemokines.

A Randomized Controlled Trial on the Effect of Luseogliflozin on Bone Microarchitecture Evaluated Using HR-pQCT in Elderly Type 2 Diabetes.

INTRODUCTION: Bone fragility is a critical issue in the treatment of elderly people with type 2 diabetes (T2D). In the Canagliflozin Cardiovascular Assessment Study, the subjects with T2D who were treated with canagliflozin showed a significant increase in fracture events compared to a placebo group as early as 12 weeks post-initiation. In addition, it has been unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitors promote bone fragility. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to prospectively evaluate the short-term effect of the SGLT2 inhibitor luseogliflozin on bone strength and microarchitecture in elderly people with T2D. METHODS: This was a single-center, randomized, open-label, active-controlled pilot trial for ≥ 60-year-old Japanese individuals with T2D without osteoporosis. A total of 22 subjects (seven women and 15 men) were randomly assigned to a Lusefi group (added luseogliflozin 2.5 mg) or a control group (added metformin 500 mg) and treated for 48 weeks. We used the second-generation HR-pQCT (Xtreme CT II®, Scanco Medical, Brüttisellen, Switzerland) before and 48 weeks after the treatment to evaluate the subjects' bone microarchitecture and estimate their bone strength. RESULTS: Twenty subjects (Lusefi group, n = 9; control group, n = 11) completed the study, with no fracture events. As the primary outcome, the 48-week changes in the bone strength (stiffness and failure load) estimated by micro-finite element analysis were not significantly different between the groups. As the secondary outcome, the changes in all of the cortical/trabecular microarchitectural parameters at the radius and tibia from baseline to 48 weeks were not significantly different between the groups. CONCLUSIONS: In the pilot trial, we observed no negative effect of 48-week luseogliflozin treatment on bone microarchitecture or bone strength in elderly people with T2D. TRIAL REGISTRATION: UMIN-CTR no. 000036202 and jRCT 071180061.

Association between physical performance and bone mass in community-dwelling postmenopausal Japanese women: The Unzen study.

BACKGROUND: Low bone mass is an independent risk factor for osteoporotic fractures. We examined the association between physical performance and bone mass using quantitative ultrasound in community-dwelling postmenopausal Japanese women. METHODS: We conducted a cross-sectional study on 524 community-dwelling postmenopausal Japanese women who were not being administered osteoporosis medications. Physical performance was assessed on the basis of grip strength, chair stand time, and functional reach. The stiffness index was measured as a quantitative ultrasound parameter for heel bone mass. RESULTS: Physical performance, assessed by grip strength, chair stand time, and functional reach, and the stiffness index significantly decreased with age (both p<0.001). The multiple linear regression analysis showed that grip strength (p = 0.001), chair stand time (p = 0.004), and functional reach (p = 0.048) were significantly associated with the stiffness index after adjusting for age, body mass index, smoking, drinking, and exercise. CONCLUSIONS: Physical performance was significantly associated with heel bone mass in community-dwelling postmenopausal Japanese women.

Effects of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate on cortical and trabecular bone of vertebra and proximal femur in postmenopausal women with fragility fracture: Sub-analysis by quantitative computed tomography from the TERABIT study.

PURPOSE: The effects of daily teriparatide (D-PTH, 20 µg/day), weekly high-dose teriparatide (W-PTH, 56.5 µg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT). METHODS: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment. RESULTS: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %). CONCLUSIONS: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.