Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies.

BACKGROUND: The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors. PATIENTS AND METHODS: Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1-14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing. RESULTS: Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr(705)) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure. CONCLUSION: OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing, compared with intermittent dosing, suggest that less frequent dosing should be explored. CLINICALTRIALSGOV IDENTIFIER: NCT01184807.

Body fat composition impacts the hematologic toxicities and pharmacokinetics of doxorubicin in Asian breast cancer patients.

Body surface area (BSA)-based dosing leads to wide inter-individual variations in drug pharmacokinetics and pharmacodynamics, whereas body composition has been shown to be a more robust determinant of efficacy and toxicity of certain chemotherapeutic agents. We correlated various parameters of body composition with doxorubicin pharmacokinetics and hematologic toxicities in Asian patients with locally advanced or metastatic breast cancer. Our analysis included 84 patients from two studies who received pre- or post-operative single-agent doxorubicin; pharmacokinetic parameters were available for 44 patients. Body composition parameters were derived from CT cross-sectional images and population pharmacokinetic analysis was conducted using mixed-effects modeling. Higher intra-abdominal fat volume and fat ratio (intra-abdominal:total abdominal fat volume) correlated with greater incidence of grade 4 leukopenia on cycle 1 day 15 (mean intra-abdominal fat volume: 97.4 ± 46.5 cm(3) vs 63.4 ± 30.9 cm(3), p = 0.014; mean fat ratio: 0.43 ± 0.11 vs 0.33 ± 0.09, p = 0.012, grade 4 vs grade 0-3 leukopenia). On subset analysis, this relationship was maintained even in underweight patients. Concordantly, there were positive correlations between doxorubicin AUC and intra-abdominal fat volume as well as total abdominal fat volume (r (2) = 0.324 and 0.262, respectively, all p < 0.001). BSA and muscle volume did not predict for doxorubicin pharmacokinetics or toxicities. High-intra-abdominal fat volume but not BSA predicted for greater doxorubicin exposure and hematologic toxicities, suggesting that body composition is superior to BSA in determining doxorubicin pharmacokinetics and pharmacodynamics. Body composition has an emerging role in chemotherapy dose determination.

Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.

Back-translating GWAS findings to animal models reveals a role for Hgfac and Slc39a8 in alcohol and nicotine consumption.

Alcohol and tobacco are the most commonly used addictive substances, with high comorbidity rates between alcohol use disorder and tobacco use disorder. Risk for alcohol and nicotine addiction is highly heritable, and they share common genetic factors. A GWAS in over 1 million individuals has revealed 566 genetic variants in 406 loci associated with multiple stages of alcohol and tobacco use. Three novel genes-SLC39A8, GRK4 and HGFAC-within loci associated with altered alcoholic drinks per week (ADW) or cigarettes per day (CPD) were selected to further study their role in alcohol and tobacco use disorder. The role of these genes was assessed using the two-bottle choice addiction paradigm in transgenic mice for each of the genes. We found significant decreases in chronic alcohol consumption and preference in female Hgfac knockout (KO) mice, and decreased nicotine preference in male Hgfac KO compared with wild-type (WT) mice. Additionally, male Slc39a8 hypomorph mice showed greater overall nicotine preference compared with WT mice, while no differences were detected for Grk4 KO mice in alcohol or nicotine consumption and preference in either sex. Thus, this study implicates Hgfac and Slc39a8 in alcohol and tobacco use in a sex-specific manner.

Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy.

BACKGROUND: Tumour expression of cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), erythroblastic leukaemia viral oncogene homologue-2 (ErbB2), Ki-67 and p53 in breast cancer are associated with poorer outcomes. We investigated in vivo changes of these proteins with neoadjuvant chemotherapy. PATIENTS AND METHODS: Four core biopsies were taken from 100 breast cancer patients at baseline, during and upon completion of neoadjuvant chemotherapy. Immunohistochemical expression of these proteins were evaluated and correlated with clinicopathological features, clinical response and progression-free survival (PFS). RESULTS: There was a statistically significant change from positivity to negativity in COX-2 expression with chemotherapy (P = 0.002), predominantly in clinical responders (P = 0.002). COX-2-positive tumours that remained positive had shorter PFS than those that turned negative. Estrogen receptor (ER)+ and COX-2+ tumours at baseline that remained COX-2+ fared worse than those that became COX-2 negative (PFS 27 versus 52 months, P = 0.002). No significant changes in IHC expression were observed for ER, progesterone receptor, ErbB2, EGFR, p53 or Ki67. CONCLUSIONS: Chemotherapy induced change in COX-2 expression from positivity to negativity predominantly among clinical responders and is associated with longer PFS. Interaction between COX-2 and ER was observed, suggesting that some hormone receptor-positive patients may benefit from combining COX-2 inhibition with hormonal therapy.

Ambiguity hindering self-management and prevention of osteoporosis in post-menopausal women.

As osteoporosis relies largely on self-managed prevention and adherence to long-term treatment regimens, it is imperative that those at risk understand the disease that they are attempting to prevent. Ambiguity regarding osteoporosis and reluctance to take anti-osteoporosis medication (AOM) as well as calcium was noted in Australian post-menopausal women. This may lead to underestimating women's own risk of osteoporosis and fracture. INTRODUCTION: Fragility fractures caused by osteoporosis have been known to inflict significant personal and financial burden on individuals and society. As treatment of osteoporosis relies largely on self-managed prevention and adherence to long-term AOM regimens, it is imperative that women have a sound understanding of the disease that they are attempting to prevent. Much can also be gained from qualitatively exploring the level of osteoporosis knowledge particularly in post-menopausal women who are at greater risk of osteoporosis and fractures. This study thus aims to determine what post-menopausal Australian women know about osteoporosis and osteoporosis prevention. METHOD: Six focus group sessions, using purposive sampling, were conducted with 23 female participants (mean age 68 years (range 62-83)). Women responded to a series of open-ended questions regarding their knowledge about osteoporosis. The audiotaped focus groups were transcribed verbatim and analysed using a thematic analysis framework. RESULTS: Three key themes were identified: ambiguity about the nature of osteoporosis, ambiguity about osteoporosis prevention and reluctance to take AOM and calcium. CONCLUSION: Ambiguity associated with risk and prevention may provide women with a false sense of security that they are adequately acting to prevent the disease. Underestimation of their risk of osteoporosis and fracture as well as reluctance associated with AOM may be barriers to osteoporotic fracture prevention.

Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice.

BACKGROUND: The use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion. METHODS: Adult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine. RESULTS: Mice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone. CONCLUSIONS: Our data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone.

Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats.

To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.

Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study.

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p<0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076). CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (<3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.

Two kappa immunoglobulin light chains are secreted by an anti-DNA hybridoma: implications for isotypic exclusion.

An anti-DNA hybridoma derived from an MRL/lpr mouse secretes two different kappa light chains in combination with a single heavy chain. Multiple single cell clones express and secrete immunoglobulin containing both kappa light chains. The N-terminal protein sequences of the light chains correspond to sequences predicted from functionally rearranged mRNAs subjected to reverse transcription and amplified by polymerase chain reaction (PCR). Karyotype analysis of the hybridoma indicates a clonal line derived from the fusion of two cells. By amino acid sequence comparison and PCR analysis, both functional kappa light chains are derived from the MRL/lpr spleen. The two functional light chain cDNAs were cloned and co-transfected into COS-7 cells with the heavy chain cDNA. Only one of the light chains in combination with mAb 3E10 heavy chain confers anti-DNA reactivity. The presence of two separate kappa light chains and, therefore, two separate antigen receptors on a single B cell may have ramifications for both polyclonal activation and toleration of lupus B cells.

The Impact of Fracture Incidence on Health Related Quality of Life among Community-Based Postmenopausal Women.

This prospective study aimed to examine the impact of fracture incidence on health-related quality of life (HRQOL) among postmenopausal women. Study subjects were Australian female community-dwellers in the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were collected annually from 2007 to 2010. Outcomes were the Medical Outcomes Study Short Form-36 (SF-36 physical function (SF36PFS) and vitality (SF36VS) scores), European Quality of Life (EQ-5D), and self-reported general health (GH) of excellent/good. Questionnaires were divided into prior to, the 1st, the 2nd, and the 3rd year after incident fracture assessments. Generalized linear models with generalised estimating equations (GEE) were employed for the analysis. The 2,872 participants (age: median 65; interquartile range 60-73 years) provided a total of 10,436 assessments including 266, 165 and 76 assessments for the 1st, the 2nd, and the 3rd year after incident fracture, respectively. Multivariate adjustments showed reductions in HRQOL measures peaking at the 1st year for SF36VS (coefficient -3.0; 95% CI: -5.1, -0.8) and EQ-5D (coefficient -0.03; 95% CI: -0.06, -0.00) and at the 2nd year for SF36PFS (coefficient -3.0; 95% CI: -5.6, -0.5) and GH (odds ratio 0.92; 95% CI: 0.70, 1.19). Fracture incidence reduced HRQOL including vitality and physical function among relatively young, healthy postmenopausal women and the reduction in European Quality of Life measure was clinically important.

Impact of intraoperative echocardiography on surgical management of congenital heart disease.

Intraoperative echocardiography was performed by epicardial, 2-dimensional, low- and high-pulsed repetition frequency, continuous-wave Doppler and color flow mapping in 50 patients. Forty studies were performed before and 44 studies after cardiopulmonary bypass. Studies before cardiopulmonary bypass agreed with preoperative evaluation. After cardiopulmonary bypass, studies revealed that 11 of 25 patients who underwent repair of ventricular septal defects had residual ventricular septal defects, and 1 of 25 patients who underwent atrial septal repair had 1 residual atrial communication. One patient with a "Swiss cheese" ventricular septum underwent repeat cardiopulmonary bypass to close residual ventricular septal defects. The patient with a residual atrial communication required immediate reoperation because of a right to left shunt after a modified Fontan procedure. Eight of 10 remaining residual ventricular septal defects spontaneously closed 1 to 41 days after operation. Assessment of postcardiopulmonary bypass and postoperative valvular regurgitation in 21 valves revealed good correlation (p less than 0.01). However, 1 patient required reoperation for mitral valve replacement on the sixth postoperative day. The correlation was fair between postcardiopulmonary bypass and postoperative residual stenotic pressure gradients in 12 surgically repaired stenotic lesions. This study shows that little additional information is added to a comprehensive preoperative evaluation by precardiopulmonary bypass intraoperative echocardiography. Postcardiopulmonary bypass intraoperative echocardiography is useful in identifying residual shunts. Assessment of stenotic gradients and valvular regurgitation must be interpreted in light of a changing hemodynamic state.

Eosinophilic fasciitis in association with chronic vasculitic-like leg ulcerations.

Vasculitic lesions are not generally associated with eosinophilic fasciitis. Eosinophilic fasciitis is reported to be a syndrome distinct from progressive systemic sclerosis (PSS). More recent studies, however, note overlapping features in the clinical, pathologic, and laboratory findings of eosinophilic fasciitis and scleroderma. We report a typical presentation of eosinophilic fasciitis that developed vasculitic-like leg ulcerations as seen in scleroderma.

A review of computed tomography in the diagnosis of intestinal and mesenteric injury in pediatric blunt abdominal trauma.

OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of the computed tomography (CT) scan in the diagnosis of clinically significant intestinal and mesenteric injury in pediatric blunt abdominal trauma. PATIENTS: The records of 145 children who presented to a tertiary care pediatric hospital between 1987 and 1994 were reviewed retrospectively. All had experienced single or multiple injuries and underwent CT as part of the trauma assessment. METHODS: The patients were divided into two cohorts, based on the results of the initial CT scan: either positive (n = 20) or negative (n = 152) for evidence of intestinal or mesenteric injury. The two cohorts were similar with respect to age, trauma score, and timing of CT scan. The outcome of surgical (n = 23) and conservative management (n = 122) was compared with the initial CT scan results. (Some of the laparotomies were for solid-organ injury only.) RESULTS: The sensitivity of the CT scan in the diagnosis of clinically significant intestinal and mesenteric injury is 0.93. The specificity and positive and negative predictive values are 0.95, 0.65, and 0.99, respectively. CONCLUSION: The CT scan is an excellent test to screen for clinically significant intestinal and mesenteric injury in pediatric patients with blunt abdominal trauma. Because of the lower positive value, other clinical and diagnostic imaging information may help to improve diagnostic accuracy. Most importantly, CT rarely misses a significant intestinal or mesenteric injury.

Acute appendicitis in an incarcerated inguinal hernia.

A preterm infant with acute appendicitis in an incarcerated inguinal hernia is described. We suggest that extraluminal compression of the neck of a hernial sac caused by incarceration may be a predisposing factor for appendicitis.

Microbial production of polyhydroxyalkanoates by bacteria isolated from oil wastes.

A Gram-positive coccus-shaped bacterium capable of synthesizing higher relative molecular weight (M(r)) poly-hydroxybutyrate (PHB) was isolated from sesame oil and identified as Staphylococcus epidermidis (by Microbial ID, Inc., Newark, NJ). The experiment was conducted by shake flask fermentation culture using media containing fructose. Cell growth up to a dry mass of 2.5 g/L and PHB accumulation up to 15.02% of cell dry wt was observed. Apart from using single carbohydrate as a sole carbon source, various industrial food wastes including sesame oil, ice cream, malt, and soya wastes were investigated as nutrients for S. epidermidis to reduce the cost of the carbon source. As a result, we found that by using malt wastes as nutrient for cell growth, PHB accumulation of S. epidermidis was much better than using other wastes as nutrient source. The final dried cell mass and PHB production using malt wastes were 1.76 g/L and 6.93% polymer/cells (grams/gram), and 3.5 g/L and 3.31% polymer/cells (grams/gram) in shake flask culture and in fermentor culture, respectively. The bacterial polymer was characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, Fourier transform infrared, and differential scanning calorimetry. The results show that with different industrial food wastes as carbon and energy sources, the same biopolymer (PHB) was obtained. However, the use of sesame oil as the carbon source resulted in the accumulation of PHB with a higher melting point than that produced from other food wastes as carbon sources by this organism under similar experimental conditions.

House dust mite fauna in the Klang Valley, Malaysia.

Allergy to house dust mites (HDM) is an important cause of asthma and rhinitis in Malaysia. This study was carried out to evaluate the dust mite fauna in the Klang Valley. Dust samples were collected from 20 houses from March 1994 to February 1995. Thirty-three dust samples from mattresses were examined monthly for the occurrence of HDM. A total of 22 species in 9 families of HDM was identified. The most common and densely populated species was Blomia tropicalis with an average density of 8,934 mites/g of dust. Dermatophagoides pteronyssinus was the next in abundance, followed by Malayoglyphus intermedius. All houses surveyed were found to be infested with HDM and every house had at least 6 species of HDM. B. tropicalis and D. pteronyssinus were found in all mattresses. HDM in the Klang Valley were found to be highly prevalent and present in high densities. In this study, counts of D. pteronyssinus was found to exceed the proposed exposure threshold of 500 mites/g dust, for triggering acute asthma. Although counts of B. tropicalis exceeded D. pteronyssinus, no conclusion could be made because there is currently no exposure threshold for triggering acute asthma, for this species. Monthly distribution of B. tropicalis and D. pteronyssinus showed 2 peaks and 4 peaks, respectively. The major peak for D. pteronysinus was in January 1995 whereas for B. tropicalis, the major peak was more variable and occurred between November 1994 to January 1995. Both the species showed minor peak in April 1994.

Concern and risk perception: effects on osteoprotective behaviour.

This study aimed to determine the effect that level of concern for osteoporosis, as well as self-perceived risk of osteoporosis and fracture, has on supplementation use, seeking medical advice, bone mineral density (BMD) testing, and antiosteoporosis medication (AOM) use. Study subjects were 1,095 female Australian participants of the Global Longitudinal study of Osteoporosis in Women (GLOW) untreated for osteoporosis at baseline. Study outcomes from self-administered questionnaires included calcium and vitamin D supplementation, self-reported seeking of medical advice regarding osteoporosis, BMD testing, and AOM use in the last 12 months at the late assessment. Logistic regression was used in the analysis. Concern significantly increased the likelihood of seeking medical advice and, however, had no significant impact on screening or treatment. Heightened self-perceived risks of osteoporosis and fracture both significantly increased the likelihood of seeking medical advice and BMD testing while elevated self-perceived risk of fracture increased AOM use. Supplementation use was not significantly associated with concern levels and risk perception. Concern and risk perceptions to osteoporosis and fracture were significantly associated with certain bone-protective behaviours. However, the disconnect between perceived osteoporosis risk and AOM use illustrates the need to emphasize the connection between osteoporosis and fracture in future education programs.

Concern and risk perception of osteoporosis and fracture among post-menopausal Australian women: results from the Global Longitudinal Study of Osteoporosis in Women (GLOW) cohort.

PURPOSE: The purpose of this study is to identify factors associated with concern and perception of risks of osteoporosis and osteoporotic fractures and determine whether bone mineral density (BMD) testing influenced concern and risk perception. METHODS: Study subjects (n = 1,082, age 55-94 years) were female Australian participants of the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were sent annually from 2007 to 2010. Study outcomes included 'concern about osteoporosis', 'perception of getting osteoporosis' and 'perception of fracture risk' compared to similar aged women. The closest post-BMD testing or baseline questionnaires were used for women with and without BMD testing, respectively. Multinomial logistic regression was used for the analysis. RESULTS: BMD testing, prior fracture after age 45, younger age and lower self-reported general health were significantly associated with being 'very' or 'somewhat concerned' about osteoporosis and having a 'much higher' or 'little higher' risk perception of osteoporosis and fractures. A poorer BMD result was associated with higher concern and higher risk perceptions. The presence of comorbidities, having ≥2 falls in the preceding year and maternal osteoporosis were associated with higher concern. Maternal osteoporosis, presence of comorbidities, weight loss of ≥5 kg in the preceding year and low body mass index were associated with higher perceptions of osteoporosis risk. CONCLUSION: Women's concern and risk perception of osteoporosis and osteoporotic fractures were reasonably well founded. However, increasing age, height loss, smoking and drinking were not associated with concern and perception despite being known osteoporosis risk factors. These factors should be considered in planning for education and awareness raising programmes.