Management of menopausal symptoms in breast cancer patients

In breast cancer patients, menopausal symptoms such as hot flashes, urogenital problems, musculoskeletal symptoms and cognitive dysfunction are common, regardless of age at diagnosis. They affect quality of life and systemic therapy will worsen this. Endocrine and/or chemotherapy may induce temporary or permanent ovarian failure and can exacerbate these symptoms. Hormone therapy (HT) has been studied in breast cancer survivors, but safety has been questioned. The HABITS trial investigating estrogen-based HT, as well as the LIBERATE trial investigating tibolone, found a reduction in disease-free survival for those treated. Alternative strategies are needed, as menopause symptoms may reduce compliance with breast cancer treatments. This article reviews recently published strategies to tackle menopausal problems in breast cancer patients. Antidepressants may help with hot flashes. Acupuncture and hypnosis can also be used but the evidence is conflicting. For urogenital problems vaginal moisturizers or topical estrogens can be employed. A musculoskeletal syndrome induced by aromatase inhibitors (AIs) is frequently encountered and currently there are no effective treatment strategies. Bisphosphonates reduce AI-induced bone resorption and can also increase disease-free and overall survival. Standard-dose endocrine and chemotherapy are associated with a decline in cognitive function.     

Alendronate treatment results in similar levels of trabecular bone remodeling in the femoral neck and vertebra

Summary  We aimed to determine whether trabecular bone in sites that have different surface-based remodeling rates, the femoral neck and vertebra, are differently affected by alendronate treatment. Alendronate treatment resulted in similar levels of turnover in both sites, suggesting that a lower limit of bone turnover suppression with alendronate may exist. Introduction  Bone turnover suppression in sites that already have a low surface-based remodeling rate may lead to oversuppression that could have negative effects on the biomechanical properties of bone. The goal was to determine how alendronate suppresses bone turnover at sites with different surface-based remodeling rates. Methods  Dynamic histomorphometric parameters were assessed in trabecular bone of the femoral neck and lumbar vertebrae obtained from skeletally mature beagles treated with saline (1 ml/kg/day) or alendronate (ALN 0.2 or 1.0 mg/kg/day). The ALN0.2 and ALN1.0 doses approximate, on a milligram per kilogram basis, the clinical doses used for the treatment of postmenopausal osteoporosis and Paget’s disease, respectively. Results  Alendronate treatment resulted in similar absolute levels of bone turnover in the femoral neck and vertebrae, although the femoral neck had 33% lower pre-treatment surface-based remodeling rate than the vertebra (p < 0.05). Additionally, the high dose of alendronate (ALN 1.0) suppressed bone turnover to similar absolute levels as the low dose of alendronate (ALN 0.2) in both sites. Conclusions  Alendronate treatment may result in a lower limit of trabecular bone turnover suppression, suggesting that sites of low pre-treatment remodeling rate are not more susceptible to oversuppression than those of high pre-treatment remodeling rate.     

Gammadelta T-cells: potential regulators of the post-burn inflammatory response

Severe burn induces an immunopathological response that contributes to the development of a systemic inflammatory response (SIRS) and subsequent multiple organ failure. While, multiple immune cells type (T-cells, macrophages, neutrophils) are involved in this response, recent evidence suggests that a unique T-cell subset, gammadelta T-cells are central in the response to injury. While gammadelta T-cells represent only a small percentage of the total T-cell population, they display specific functional characteristics that uniquely position them in the immune/inflammatory axis to influence a number of important aspects of the body's response to burn. This review will focus on the potential regulator role of gammadelta T-cells in immunopathological response following burn and thereby their potential as therapeutic targets for affecting inflammation and healing.     

Reversal of hypercalcemic acute kidney injury by treatment with intravenous bisphosphonates

We present the details of three children with hypercalcemia-induced acute kidney injury (AKI). After traditional therapy with fluids, loop diuretics, steroids and calcitonin had failed to correct the hypercalcemia, they were given treatment with low doses of intravenous (i.v.) pamidronate, which resulted in normalization of serum calcium and kidney function. In one child Doppler renal ultrasound revealed dampened arterial blood flow, which resolved with normalization of serum calcium. On the basis of cumulative data and our experience, we suggest that i.v. application of bisphosphonates be moved from the second to the first line of treatment of hypercalcemic AKI.     

Bisphosphonate Use in Acute and Chronic Spinal Cord Injury: A Systematic Review

Background/Objective:

Bone density loss occurs rapidly after traumatic spinal cord injury (SCI) and is associated with low-energy fractures below the level of injury, commonly occurring around the knee. Bisphosphonates have been tested as potential agents to prevent bone loss after SCI, but no guidelines exist for clinical use of bisphosphonates in these patients. The objective of this study was to systematically review and evaluate evidence quality in studies of bisphosphonate use in patients with post-treatment follow-up of sublesional bone mineral density.

Methods:

Literature search in MEDLINE/PubMed and ISI database using key words bisphosphonates, spinal cord injury, quadriplegia, paraplegia, and tetraplegia.

Results:

The search identified 6 experimental studies and 1 quasi-experimental study of bisphosphonate therapy in patients with acute and chronic SCI. The studies were small and of fair or poor quality, and none included fracture outcomes. Mild attenuation of bone density loss with acute administration of bisphosphonates after SCI was found at some measurement sites but was not always maintained during follow-up.

Conclusions:

Data were insufficient to recommend routine use of bisphosphonates for fracture prevention in these patients. Current studies are limited by heterogeneity of patient populations and outcome measures. Uniform bone density measurement sites with rigorous quality control and compliance monitoring are needed to improve reliability of outcomes. Future studies should address specific populations (acute or chronic SCI) and should assess fracture outcomes.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

Multimodal imaging and treatment of bone metastasis

The role of molecular imaging in pre-clinical research is continuously evolving. Particularly in small animal models in biomedical research, optical imaging technologies are frequently used to visualize normal as well as aberrant cellular processes at a molecular-genetic or cellular level of function. Also in cancer metastasis research, whole body bioluminescent and fluorescent imaging techniques have become indispensable tools that allow non-invasive and real-time imaging of gene expression, tumor progression and metastasis, and response to therapeutic intervention. In this paper, we discuss the use of optical imaging strategies—either alone or in combination with CT- to study intrabone tumor growth, tumor progression and to monitor efficacy of therapeutic agents in metastatic bone disease.