Volume 12 · Number 1 · March 2020
- Risk factors for incident fracture in patients with breast cancer treated with aromatase inhibitors: B-ABLE cohort [7-13]
- Differences in bone mineral metabolism normocalcemic primary hyperparathyroidism with respect to classical primary hyperparathyroidism [14-19]
- Effects of bazedoxifene treatment on the bone quality of ovariectomized rats [20-27]
- Influence of high-concentration hyperbaric oxygen therapy on bone metabolism [28-31]
Few medical areas have changed as much through the last decades as the treatment of breast cancer (BC). From Halsted’s theory of the progression of an initially local disease, with a first loco-regional and then metastatic extension, to the most recent studies in molecular biology that identify the gene personality of each tumor, there have been many advances. Old TNM classification originally designed for solid tumors have been abandoned and all areas related to hormonal dependence and gene expression of each tumor have grown in importance. All this is aimed at better facing a global therapeutic approach.
Almost 20 years ago, an important biological research laboratory provided us with a detailed study of the basal estradiol levels of the patients in the placebo group of the MORE study . An increased risk of breast cancer associated with raised serum estradiol levels was demonstrated, confirming the previous results on the hormonal dependence of this neoplasm. With the introduction of chemotherapy (QMT) in the final decade of the last century, the general mortality of women from breast cancer was reduced in all western countries. At the time, and just a few years later, the implementation of massive early detection programs at the population level facilitated an increase in the diagnosis of tumors in early stages.
Risk factors for incident fracture in patients with breast cancer treated with aromatase inhibitors: B-ABLE cohort
Currently, aromatase inhibitors (AI) are used as first-line adjuvant therapy for women diagnosed with breast cancer with positive hormonal receptors. Although its effectiveness in reducing the risk of recurrence and mortality is well known , AIs have also been associated with side effects that can negatively affect the patient’s quality of life, adherence to treatment and associated mortality .
In AI treatment, there is a marked reduction in circulating estrogens in postmenopausal women by blocking the conversion by the enzyme aromatase from androgens to estrogens. This action leaves the woman without residual estrogens, such as estradiol and estrone, after menopause. One of the most common side effects is accelerated bone loss, which is associated with an increased risk of osteoporotic fractures [3,4]. Along these lines, there are different meta-analyzes that include randomized controlled clinical trials that have shown an association between prolonged treatment with AI and an increased risk of bone fractures, with an increase between 34% and 59% [5,6].
Differences in bone mineral metabolism normocalcemic primary hyperparathyroidism with respect to classical primary hyperparathyroidism
Primary hyperparathyroidism (HPT) is a very common bone mineral metabolic disease consisting of autonomous overproduction of parathyroid hormone (PTH), which leads to an increase in serum calcium . It is the most frequent cause of hypercalcemia.
A lesser known clinical variant of HPT is the so-called “normocalcemic primary hyperparathyroidism” (NHPT), which has normal blood calcium levels and elevated parathyroid hormone (PTH) values, not knowing the mechanism by which this differential fact occurs [2-4]. These patients do not have clear causes that justify secondary elevations of PTH such as chronic renal damage , vitamin D deficiency (less than 30 ng/ml) , renal hypercalciuria or drugs . Although NHPT was first formally recognized in the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008 , all clinical features are not yet known, particularly with regard to its epidemiology, natural history, management and prognosis [9,10]. Therefore, this clinical variety of the disease is less studied  and there is less bibliography. All of which has motivated us to carry out this study.
Selective estrogen-receptor modulators (SERMs) are synthetic, nonsteroidal agents with estrogenic agonist-antagonist activity in different target tissues . Their estrogenic responses are mediated by estrogen receptors (α and β). SERMs may present agonistic or antagonistic behavior depending on the tissue type [2,3]. In general, SERMs exhibit agonist activity in the liver, the digestive tube, the skeleton and the heart, but antagonist activity in the breast. In the uterus some SERMs manifest agonist activity while others show an antagonist behavior . Several co-regulatory proteins modify the behavior of the SERMs on gene expression and contribute to their tissue-selective pharmacology.
Tamoxifen is a SERM used as a mammary antiestrogen for preventing and treating breast cancer with estrogen agonistic activity in the uterus. Raloxifene has been used for the prevention and treatment of osteoporosis and prevents breast cancer but presents some estrogenic activity . Bazedoxifene is a 3rd generation SERM with agonistic effects on the bone and additional positive effects on lipids, the uterus and the breast tissue [5,6].
Oxygen is required to produce cellular energy and is involved in numerous processes, such as enzymatic activation, molecular signaling and regulation of gene expression . Also in angiogenesis, the maintenance of hematopoietic stem cells and bone formation . In fact, changes in the partial pressure of oxygen can influence the function of osteoblasts and osteoclasts . In hypoxia, bone formation and mineralization decreases, while resorption increases [4-6]. In the opposite direction, hyperoxia could have a beneficial effect on the bone. Treatment with high concentration of oxygen in the hyperbaric chamber has proven useful in osteomyelitis and osteonecrosis of the jaw caused by radiotherapy or by the use of bisphosphonates [7-9]. HC accelerates osteogenic differentiation of mesenchymal cells and decreases the activation of osteoclasts [10-12].
In this work we wanted to analyze the actions of oxygen at high concentration in HBO on the expression of genes related to bone metabolism in osteoblastic cell lines and human bone [5,6,13,14].
To the Editor:
Current scientific evidence and practical clinical guidelines recommend primary and secondary prevention of fragility fractures in geriatric patients [1,2]. A personal history of fragility fractures significantly increases the risk of new fractures. Up to 33% of patients with a femur fracture had suffered a previous fracture. Among the various fractures due to fragility, the femur is the most prevalent and presents the most repercussions (clinical, functional and social) in patients over 65 years of age, with the resulting depletion of health resources . The worldwide trend is estimated to rise from 1.7 million femoral fractures in 1990 to 6 million in 2050 .
In 2011, the Fractures Working Group of the Scientific Advisory Committee of the International Osteoporosis Foundation stressed the importance of coordination between orthopedics, osteoporosis services, fall units, patient, family, geriatrician and Primary Care physician. This multidisciplinary action was consolidated in the so-called “coordinated services for the treatment of fractures” or Fracture Liaison Services (FLS) that were initially implemented in the United Kingdom, Europe, Australia, Canada and the USA , with very good results.