[18F]Sodium fluoride PET-MRI detects increased metabolic bone response to whole-joint loading stress in osteoarthritic knees.

OBJECTIVE: Altered joint function is a hallmark of osteoarthritis (OA). Imaging techniques for joint function are limited, but [18F]sodium fluoride (NaF) PET-MRI may assess the acute joint response to loading stresses. [18F]NaF PET-MRI was used to study the acute joint response to exercise in OA knees, and compare relationships between regions of increased uptake after loading and structural OA progression two years later. METHODS: In this prospective study, 10 participants with knee OA (59 ± 8 years; 8 female) were scanned twice consecutively using a PET-MR system and performed a one-legged squat exercise between scans. Changes in tracer uptake measures in 9 bone regions were compared between knees that did and did not exercise with a mixed-effects model. Areas of focally large changes in uptake between scans (ROIfocal, ΔSUVmax > 3) were identified and the presence of structural MRI features was noted. Five participants returned two years later to assess structural change on MRI. RESULTS: There was a significant increase in [18F]NaF uptake in OA exercised knees (SUV P < 0.001, KiP = 0.002, K1P < 0.001) that differed by bone region. CONCLUSION: There were regional differences in the acute bone metabolic response to exercise and areas of focally large changes in the metabolic bone response that might be representative of whole-joint dysfunction.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.

Assessment of quantitative [18F]Sodium fluoride PET measures of knee subchondral bone perfusion and mineralization in osteoarthritic and healthy subjects.

OBJECTIVE: Molecular information derived from dynamic [18F]sodium fluoride ([18F]NaF) PET imaging holds promise as a quantitative marker of bone metabolism. The objective of this work was to evaluate physiological mechanisms of [18F]NaF uptake in subchondral bone of individuals with and without knee osteoarthritis (OA). METHODS: Eleven healthy volunteers and twenty OA subjects were included. Both knees of all subjects were scanned simultaneously using a 3T hybrid PET/MRI system. MRI MOAKS assessment was performed to score the presence and size of osteophytes, bone marrow lesions, and cartilage lesions. Subchondral bone kinetic parameters of bone perfusion (K1), tracer extraction fraction, and total tracer uptake into bone (Ki) were evaluated using the Hawkins 3-compartment model. Measures were compared between structurally normal-appearing bone regions and those with structural findings. RESULTS: Mean and maximum SUV and kinetic parameters Ki, K1, and extraction fraction were significantly different between Healthy subjects and subjects with OA. Between-group differences in metabolic parameters were observed both in regions where the OA group had degenerative changes as well as in regions that appeared structurally normal. CONCLUSIONS: Results suggest that bone metabolism is altered in OA subjects, including bone regions with and without structural findings, compared to healthy subjects. Kinetic parameters of [18F]NaF uptake in subchondral bone show potential to quantitatively evaluate the role of bone physiology in OA initiation and progression. Objective measures of bone metabolism from [18F]NaF PET imaging can complement assessments of structural abnormalities observed on MRI.

Prevalence of muscle dysfunction concomitant with osteoporosis in a home-dwelling Danish population aged 65-93 years - The Copenhagen Sarcopenia Study.

INTRODUCTION: As life expectancy increases, a growing percentage of older individuals with age-related diseases such as osteoporosis and sarcopenia are expected. Patients with both conditions, i.e. patient with osteosarcopenia, are suggested to have a higher risk of fall and fracture compared to individuals with either condition. AIM: To investigate the potential relationship between low bone mineral density (BMD) and muscle dysfunction in a Danish cohort of older home-dwelling individuals. Furthermore, to examine the prevalence of osteosarcopenia and alterations in prevalence depending on cut-off values chosen. METHOD: Measures of BMD, relative appendicular lean mass and hand grip strength were assessed in 529 individuals aged 65+ from the population-based cross-sectional Copenhagen Sarcopenia Study (CSS). Osteoporosis was diagnosed according to the World Health Organization guidelines. Sarcopenia was diagnosed in accordance with the guidelines from the European Working Group on Sarcopenia in Older People (EWGSOP2) with application of cut-off values from the EWGSOP2 paper compared to cut-off values derived from a local cohort (CSS). RESULTS: 19.2% had osteoporosis (66 women and 35 men), whereas 2.7% (6 women and 8 men) and 4.2% (7 women and 15 men) had sarcopenia with application of EWGSOP2 and CSS cut-off values, respectively. Using the EWGSOP2 cut-off values, 1.5% (4 women and 4 men) were diagnosed with osteosarcopenia compared to 1.4% (4 women and 3 men) using CSS cut-off values. In the osteoporosis sub-population, 8% (EWGSOP2) and 7% (CSS) had sarcopenia and within the sarcopenia sub-population, 61.5% (EWGSOP2) and 33.3% (CSS) had osteoporosis. At all sites, BMD was lower among individuals with sarcopenia and sarcopenia increased the risk of osteoporosis (odds ratios: EWGSOP2: 7.3 (p < 0.001) and CSS: 2.2 (ns)). CONCLUSION: Osteosarcopenia was present in 1.5% of a group of healthy home-dwelling older individuals. Notably, individuals with sarcopenia had lower BMD and a higher risk of osteoporosis, whereas the opposite (prevalence of sarcopenia in individuals with osteoporosis) was not as frequent. Our data indicate that screening for sarcopenia and osteoporosis should be performed simultaneously in older individuals at high risk of falls and fractures. However, further studies with outcome-related results are needed to identify optimal measures of osteosarcopenia and cut-off values for sarcopenia.

The effect of hormone replacement therapy and exercise on cardiovascular disease risk factors in postmenopausal women.

Following menopause, women show an increased risk of heart disease to a level equal that of men. This elevated risk is thought to be due, at least partly, to changes in blood lipid and fibrinogen levels. The purpose of this article is to review the published research on the relationship between both exercise and hormone replacement with regards to common cardiovascular disease (CVD) risk factors and the relative importance of each. Menopause is associated with increased total serum cholesterol, triglycerides and fibrinogen, and a decrease in high density lipoprotein (HDL) cholesterol levels. The major reason for these changes following menopause is believed to be a result of fluctuations in hormonal status, primarily a deficiency in estrogen. Intervention may be justified since estrogen replacement therapy has been shown to decrease the risk of developing CVD and to have a significant impact on many of the CVD risk factors. The results vary from study to study, but generally estrogen replacement has been found to decrease total cholesterol and fibrinogen, while increasing HDL cholesterol and triglycerides. All of these changes, other than the increase in triglycerides, are seen as positive. The addition of progestogen to estrogen may negate some of the beneficial changes of estrogen, most notably the increase in HDL cholesterol levels. However, progestogen has also been reported to offset the increase in triglycerides seen with unopposed estrogen replacement. Thus, there are contradictory effects (both positive and negative) of hormone replacement on CVD risk factors in women. Regular aerobic exercise and resulting improvements in cardiorespiratory fitness have consistently been shown as preventive of CVD. This decreased CVD risk is in part because of the impact of exercise on blood lipids and fibrinogen. Increased aerobic exercise is thought to improve the risk profile, mainly through an increase in HDL cholesterol levels and decreases in triglycerides and fibrinogen. Unfortunately, the majority of research supporting the effects of exercise on CVD risk factors has been done on men. Even when research has included women, very few studies have focused on postmenopausal women. However, the research done on postmenopausal women points to a significantly improved CVD risk factor profile with regular cardiorespiratory exercise.

Cardiorespiratory fitness and cardiovascular disease risk factors in postmenopausal women.

PURPOSE: The purpose of the present study was to determine if individuals with high levels of cardiorespiratory fitness have better levels of the cardiovascular disease (CVD) risk factors of total cholesterol (TC), HDL cholesterol (HDL), total cholesterol/HDL cholesterol ratio (TC/HDL), triglycerides (TG), and fibrinogen (FIB) when compared with those with low fitness, in 283 nonsmoking, postmenopausal women. Second, we examined the relation between fitness and CVD risk after controlling for use of hormones and other possible confounding factors. METHODS: These analyses were done on a subset of nonsmoking, postmenopausal women in the Aerobics Center Longitudinal Study (ACLS). Records of postmenopausal women who completed a preventive medicine physical examination between 1987 and 1995 were examined. Cardiorespiratory fitness level was determined by total treadmill time to exhaustion on a graded exercise test; CVD risk factors were assessed via blood analysis. RESULTS: On cross-sectional regression analysis, fitness was significantly associated (P < or = 0.005) with TC (r2 = 0.08), TC/HDL (r2 = 0.12), TG (r2 = 0.09), and FIB (r2 = 0.06), and an increase in HDL (r2 = 0.04). After controlling for hormone status, age, year of testing, and blood glucose, each outcome variable remained significantly associated with cardiorespiratory fitness (P < 0.05). TC/HDL and TG continued to be significantly related to cardiorespiratory fitness after adjusting for body mass index (BMI) as a control variable (P < 0.01). The lack of significance between TC, HDL, and FIB with cardiorespiratory fitness after adjusting for BMI is likely due to the biological relationship between cardiorespiratory fitness and BMI (r2 = 0.19). CONCLUSIONS: We conclude that cardiorespiratory fitness is an important independent determinant of blood lipid and FIB levels in nonsmoking postmenopausal women, with or without HRT.

The effects of acute moderate exercise on leukocyte and lymphocyte subpopulations.

The extent and duration of changes in circulating leukocyte and lymphocyte subpopulations, cortisol, and catecholamines were examined in 12 women who walked 45 min at 60% VO2max in a laboratory setting. A two-factor, 2 x 6 design with repeated measures on both factors was utilized. The first factor was condition (exercise and rest), and the second factor was time (six points of measurement over a 24-h period), with treatment order counterbalanced. The 45-min walk, in comparison with rest in a seated position, was associated with a significant but moderate leukocytosis and lymphocytosis immediately following the walk. The leukocytosis was still evident after 3 h of recovery and was primarily due to a neutrophilia. The change in lymphocyte count, relative to baseline levels and the control condition, lasted less than 1.5 h, with an increase in the natural killer (CD16 and/or CD56) and cytotoxic T cell component (CD3 and CD16 and/or CD56) (NKCT) representing approximately two-thirds of the lymphocytosis and T cells (CD5) the other third. A significant decrease in the CD4:CD8 ratio was seen, with cytotoxic/suppressor (CD8) cells increasing and helper/inducer (CD4) cells demonstrating little change in comparison with baseline. This seems to have been due to a subpopulation of CD8 (low density antigen) cells, probably natural killer cells. The 45-min walk had no effect on plasma cortisol and epinephrine levels relative to the rest condition but was associated with a moderate increase in norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

The falling grace of axillary temperatures.

This study compared axillary temperatures with either rectal or oral temperatures in 173 infants and young children. Axillary temperatures indicated a sensitivity of only 27.8% in their ability to detect fever in the febrile group. The age-old gold standard of estimating rectal temperature by adding 1 degree F to the oral and 2 degrees F to the axillary temperature was verified with afebrile group mean temperatures, but did not hold up with individual children's temperatures nor with febrile mean temperatures.

Resistance training volume and post exercise energy expenditure.

The main purpose of this study was to determine if increasing the volume of a resistance training program, while keeping the intensity the same would significantly increase the recovery energy expenditure, as measured by the excess post-exercise energy expenditure (EPEE). Fifteen resistance-trained women completed two resistance training protocols. Both protocols consisted of nine exercises performed to volitional fatigue, at the previously determined eight RM. The only difference between the two protocols was the number of sets (1-set or 3-sets). All subjects completed both protocols in a randomized and counterbalanced fashion. Energy expenditure, as determined by oxygen consumption and respiratory exchange ratio (RER), was measured continuously prior to exercise, during the exercise session, and during the entire 120 min of recovery. Fingertip blood lactate concentration was determined at baseline, immediately post-exercise, and every 30 min in recovery. The net energy expenditure during exercise was significantly greater during the 3-set protocol (661.9 +/- 43.9 kj) than the 1-set protocol (234.7 +/- 13.4 kj). However, per minute of exercise, there was no significant difference between the two protocols. During the 120 min of recovery, the net EPEE was not significantly different between the two protocols (93.3 +/- 20.1 kj following the 1-set protocol, and 94.1 +/- 7.1 kj following the 3-set protocol). However, when comparing the EPEE to the number of minutes spent in the exercise session, the 1-set protocol led to a significantly greater energy expenditure in the recovery period (1.0 +/- 0.22 kj/min) than did the 3-set protocol (0.4 +/- 0.03 kj/min). These data indicate that in previously trained women, increasing the volume of resistance training, from 1-set to 3-sets, while keeping the intensity the same will not significantly increase EPEE above what is found in a lower volume of work.

Microbial energetics.

An understanding of the mechanisms by which bacteria derive their energy is clearly important for the prediction of growth yields. Bacteria can synthesize ATP by a variety of routes, by fermentation, by oxidative phosphorylation, and possibly by the excretion of metabolic end products. The bacterium Escherichia coli has been studied extensively and a great deal is now known about the different membrane-bound multi-enzyme complexes that are responsible for oxidative phosphorylation. The efficiency of oxidative phosphorylation can vary not only between different bacteria that have adapted to particular ecological niches but also in an individual bacterium grown under different conditions or modified genetically by mutation with respect to its parent. Clearly, the concept that bacteria always grow with maximum thermodynamic efficiency is erroneous and it is important, therefore, to be able to assess the efficiency of energy conversion as well as the biochemical and genetical factors that regulate the physiological expression of energy-yielding reactions if they are to be manipulated by the investigator.

The reconstitution of oxidase activity in membranes derived from a 5-aminolaevulinic acid-requiring mutant of Escherichia coli.

1. The reconstitution of oxidase activity in cell-free extracts of a mutant of Escherichia coli K12Ymel, that require 5-aminolaevulinic acid for growth on non-fermentable carbon sources, is described. 2. The reconstitution is dependent on haematin or a haem extract from a prototrophic strain of E. coli, and the product of the reaction has been identified as NADH-reducible cytochrome b. 3. The requirement for haematin cannot be replaced by four other porphyrins. Coproporphyrin III does not inhibit the haematin-dependent reconstitution, mesoporphyrin IX and protoporphyrin IX apparently compete with haematin for a binding site on the cytochrome apoprotein(s) and deuteroporphyrin IX binds to cytochrome apoprotein(s) and cannot be subsequently replaced by haematin. 4. The properties of electron-transport particles from cell-free extracts of the mutant strain, grown aerobically in the presence or absence of 5-aminolaevulinic acid, are described. In the absence of 5-aminolaevulinic acid no detectable cytochromes are produced, and oxidase activities are lowered but there is no apparent effect on the activities of the NADH dehydrogenase and d-lactate dehydrogenase. 5. The reconstitution of oxidase activity by electron-transport particles from cells grown in the absence of 5-aminolaevulinic acid requires ATP and haematin, and the product of the reaction was identified as NADH-reducible cytochrome b. 6. It is concluded that the cytochrome apoproteins are synthesized and incorporated into the cytoplasmic membrane of E. coli in the absence of haem synthesis. The subsequent reconstitution of functional cytochrome(s) requires protohaem, but the nature of the side chain on the 2 and 4 positions of the porphyrin appears to be important.

Use of chlC-lac fusions to determine regulation of gene chlC in Escherichia coli K-12.

Gene fusions between the lac structural genes and the chlC locus were isolated, and the regulation of lac gene expression was studied. The fused lac genes were induced by nitrate anaerobically and repressed by the presence of oxygen.