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Tsuyoshi Ohishi,1 Yukihiro Matsuyama2 1Department of Orthopaedic Surgery, Enshu Hospital, Hamamatsu, Shizuoka, Japan; 2Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan Abstract: Minodronate is a third-generation bisphosphonate that was developed and approved for clinical use in osteoporosis therapy in Japan. The mechanism of action for suppressing bone resorption is the inhibition of farnesyl pyrophosphate synthase, a key enzyme in the mevalonic acid metabolic pathway of osteoclasts, to induce apoptosis of the cells. Minodronate is the strongest inhibitor of bone resorption among the currently available oral bisphosphonates. Large randomized, placebo-controlled, double-blind clinical trials have revealed an increase in bone mineral density of both the lumbar spine and femoral neck over 3 years of daily minodronate therapy and risk reduction in vertebral fractures over 2 years of therapy. The increase in bone mass and the prevention of vertebral fractures are similar to those with alendronate or risedronate. The incidence of adverse events, especially gastrointestinal disturbance, is the same as or less than that with weekly or daily alendronate or risedronate. The unique mechanism of action of minodronate via the inhibition of the P2X(2/3) receptor compared with other bisphosphonates may be an advantage in reducing low back pain in patients with osteoporosis. The monthly regimen of minodronate, introduced in 2011, is expected to have better patient adherence and longer persistence. In experimental animal models, minodronate preserved, or even ameliorated, bone microarchitectures, including microcracks and perforation of the trabeculae in the short term. The lowest incidence of bisphosphonate-related osteonecrosis of the jaw among all bisphosphonates and the lack of atypical femoral fractures attributed to its use to date, however, are partly because only a smaller population used minodronate than those using other bisphosphonates. To date, minodronate is available only in Japan. Hip fracture risk reduction has not been verified yet. More clinical studies on minodronate and its use in osteoporosis treatment, with a large number of subjects, should be conducted to verify hip fracture risk reduction and long-term results. Keywords: bisphosphonate, bone mineral density, fracture, minodronate, osteoporosis, farnesyl pyrophosphate synthase, zoledronate, bone marker, bone quality, clinical trial, long-term therapy, pain reduction

Toshiko Kaitani,1 Gojiro Nakagami,2 Junko Sugama,3 Masahiro Tachi,4 Yutaka Matsuyama,5 Yoshiki Miyachi,6 Takashi Nagase,2 Yukie Takemura,7 Hiromi Sanada2 1School of Nursing, Sapporo City University, Hokkaido, Japan; 2Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 3Department of Clinical Nursing, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; 4Department of Plastic Surgery, Tohoku University Graduate School of Medicine, Miyagi, Japan; 5Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 6Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; 7Department of Nursing, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Aims and objectives: We investigated the effectiveness and safety of an advanced pressure ulcer (PU) management protocol comprising 1) ultrasonography to assess the deep tissue, 2) use of a non-contact thermometer to detect critical colonization, 3) conservative sharp debridement, 4) dressing selection, 5) negative pressure wound therapy, and 6) vibration therapy in comparison with those of a conventional approach. Each protocol was followed by trained wound, ostomy, and continence nurses (WOCNs). Background: At present, there is no systematic PU management protocol for nurses that includes appropriate assessment and intervention techniques for deep tissue injury and critical colonization. In Japan, there is no such protocol that the nurses can follow without a physician’s orders. Design and methods: This was a prospective non-randomized controlled trial. Over a 3-week period, we evaluated the effectiveness of an advanced protocol by comparing the PU severity and healing on the basis of the DESIGN-R scale and presence of patients' discomfort. We recruited ten WOCNs to follow the advanced protocol and 19 others as controls. Statistical analysis included a linear mixed-effects model and a logistic regression model. Results: In week 0–1, the advanced protocol was significantly associated with prevention of PU deterioration. Using the linear mixed-effects model, we observed a greater decrease in the DESIGN-R score (healing) in the advanced protocol group. There were no reports of excessive bleeding, pain or infection with the advanced protocol. Conclusion: Using the advanced protocol, WOCNs detected PU severity, assessed PUs, and treated PUs safely. This protocol prevented PU deterioration and/or facilitated wound healing. Relevance to clinical practice: With proper training, WOCNs can assess and treat PUs safer and quicker than when a physician's assessment is required, leading to an improvement in wound healing and prevention of PU deterioration. Keywords: pressure ulcers, WOCN, interventions, protocols, deep tissue injury

Mitsuru Hanada, Hiroshi Koyama, Masaaki Takahashi, Yukihiro MatsuyamaDepartment of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanBackground: Osgood–Schlatter disease (OSD) is one of the common causes of knee pain in active adolescents who play sports. The common age for boys to have OSD is between 12 and 15 years and for girls, between 8 and 12 years. Radiographic studies are helpful in diagnosis and treatment of OSD.Purpose: We examine the age at onset of OSD in detail and investigate the relationship between clinical findings, radiographic bone morphology, and the severity of OSD in adolescents.Results: The average age at onset of knee pain was 12 years and 6 months – 12 years and 9 months in boys, and 12 years and 1 month in girls. Boys were significantly older than girls at onset. In addition, there were significant relationships between duration from first onset to visit to the clinic, radiographic bone stage, body morphology, and radiographic severity. The patients who delayed their visit to the clinic from the first onset of pain and who were older showed a later bone stage and more radiographic severity grade of OSD. There was significant differences concerning weight and body mass index between severity grade I and III. Conclusion: For the age at the onset of OSD, the mean age of boys was significantly older than that of girls. The patients at a later bony stage had a higher severity grade. The boys and girls with OSD who had less weight or body mass index showed less severity.Keywords: Osgood–Schlatter disease, radiographic classification, tibial tuberosity, body morphology

Psychosocial properties of oral health have been reported. The present study aimed to investigate the causal effect of complete loss of natural teeth on loneliness by using fixed-effects analysis to control for confounding factors, including unmeasured time-invariant factors. Data from older adults participating in at least 2 consecutive waves of the English Longitudinal Study of Ageing in waves 3 (2006/2007), 5 (2010/2011), and 7 (2014/2015) were analyzed (N = 18,682 observations from 7,298 individuals). The association between complete loss of natural teeth and loneliness score (ranging from 3 to 9) was examined using fixed-effect linear regression analysis adjusting for time-varying confounders, including sociodemographic and health characteristics. The prevalence of complete tooth loss was 12.7%, 12.8%, and 10.6% in waves 3, 5, and 7, respectively. Individuals who transitioned to complete tooth loss during any 2 consecutive waves had an increase in loneliness score by 0.27 (95% confidence interval [CI] 0.03, 0.52), which was greater than those who maintained natural teeth (−0.03; 95% CI −0.05, −0.01). Fixed-effects analysis adjusting for time-varying confounders revealed a significant association between complete loss of natural teeth and an increase in loneliness score by 0.31 (95% CI 0.17, 0.46). Complete loss of natural teeth among older adults in England was associated with loneliness, even after accounting for measured time-varying and (un)measured time-invariant confounders. Retaining natural teeth may reduce the risk of loneliness. [ABSTRACT FROM AUTHOR]

Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: −0.14; 95% confidence interval, −0.18 to −0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = −0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively. [ABSTRACT FROM AUTHOR]

Many studies suggest associations between oral health and cardiovascular diseases, but there is a lack of causal evidence. Exploiting exogenous variation in tooth loss in US adults due to differential childhood exposure to fluoridated water, this study investigated the causal effect of tooth loss on cardiovascular diseases. A total of 722,519 participants in the Behavioral Risk Factor Surveillance System (BRFSS) waves 2006, 2008, or 2010 (birth years 1940–1978) were included in the analytical sample. To identify the effect of tooth loss on having a history of coronary heart disease (CHD) or stroke, instrumental variable analysis exploited childhood exposure to drinking water fluoride as an instrument. The weighted prevalence of CHD and stroke histories was 5.1% and 2.1%, respectively. First-stage regression indicated that childhood exposure to drinking water fluoride was a strong instrument for the number of lost teeth in adulthood (coefficient −0.61; 95% confidence interval [CI] −0.80, −0.41; F = 37.47). The probability of CHD was significantly higher by 1.04 percentage points (95% CI 0.57, 1.50) per lost tooth. The effect of tooth loss on stroke was significant only for people aged ≥60 y (coefficient 0.93 percentage points; 95% CI 0.14, 1.71). These findings are supportive of a causal effect of tooth loss on cardiovascular diseases among US adults, particularly in older age. [ABSTRACT FROM AUTHOR]

To characterize the 'portal signal' in a nonsteady hyperglycemic state, the kinetic relationship between net hepatic glucose balance (NHGB) and either hepatic glucose load (HGL) or plasma insulin level was determined during glucose infusion using a catheter technique in 36 conscious dogs. Glucose was infused intraportally (Po group) and peripherally (Pe group) at 39, 56, and 83 [micro] mol * [kg.sup.-1] * [min.sup.-1] over 2 h. There was a linear relationship between mean NHGB and either mean HGL or plasma insulin levels at each rate in either delivery (HGL: Po r = 0.99, Pe r = 0.95; insulin: Po r = 99, Per = 0.79). The threshold levels for net hepatic glucose uptake were 3.8 and 11.7 mmol/1 for plasma glucose and 65 and 392 pmol/1 for plasma insulin, respectively. The slope of the regression line against the abscissa was four times larger in portal than in peripheral delivery (HGL: Po 0.20 vs. Pe 0.05, P < 0.05; insulin: Po 0.19 vs. Pe 0.04, P < 0.05). These results suggest that the portal signal overrules the threshold of glucose for hepatic uptake by increasing hepatic extraction rate in a nonsteady hyperglycemic state. glucose delivery route; hepatic glucose load; insulin dependency; hepatic glucose uptake