Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

Leg Clubs - Beyond the ulcers : case studies based on participatory action research

Based on Participatory Action Research (PAR), the case studies in this paper examine the psychosocial benefits and outcomes for clients of community based Leg Clubs. The Leg Club model was developed in the United Kingdom (UK) to address the issue of social isolation and non-compliance to leg ulcer treatment. Principles underpinning the Leg Club are based on the Participatory Action Framework (PAR) where the input and involvement of participants is central. This study identifies the strengths of the Leg Club in enabling and empowering people to improve the social context in which they function. In addition it highlights the potential of expanding operations that are normally clinically based (particularly in relation to chronic conditions) but transferable to community settings in order that that they become “agents of change” for addressing such issues as social isolation and the accompanying challenges that these present, including no-compliance to treatment.

The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

Conditioning of the Achilles tendon via ankle exercise improves correlations between sonographic measures of tendon thickness and body anthropometry

Although conditioning is routinely used in mechanical tests of tendon in vitro, previous in vivo research evaluating the influence of body anthropometry on Achilles tendon thickness has not considered its potential effects on tendon structure. This study evaluated the relationship between Achilles tendon thickness and body anthropometry in healthy adults both before and after resistive ankle plantarflexion exercise. A convenience sample of 30 healthy male adults underwent sonographic examination of the Achilles tendon in addition to standard anthropometric measures of stature and body weight. A 10-5 MHz linear array transducer was used to acquire longitudinal sonograms of the Achilles tendon, 20 mm proximal to the tendon insertion. Participants then completed a series (90-100 repetitions) of conditioning exercises against an effective resistance between 100% and 150% body weight. Longitudinal sonograms were repeated immediately on completion of the exercise intervention, and anteroposterior Achilles tendon thickness was determined. Achilles tendon thickness was significantly reduced immediately following conditioning exercise (t = 9.71, P < 0.001), resulting in an average transverse strain of -18.8%. In contrast to preexercise measures, Achilles tendon thickness was significantly correlated with body weight (r = 0.72, P < 0.001) and to a lesser extent height (r = 0.45, P < 0.01) and body mass index (r = 0.63, P < 0.001) after exercise. Conditioning of the Achilles tendon via resistive ankle exercises induces alterations in tendon structure that substantially improve correlations between Achilles tendon thickness and body anthropometry. It is recommended that conditioning exercises, which standardize the load history of tendon, are employed before measurements of sonographic tendon thickness in vivo.