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 [1], AIs have also been associated with side effects that can negatively affect the patient’s quality of life, adherence to treatment and associated mortality [2].
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].

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 [1]. 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 [5], vitamin D deficiency (less than 30 ng/ml) [6], renal hypercalciuria or drugs [7]. Although NHPT was first formally recognized in the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008 [8], 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 [11] 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 [1]. 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 [1]. 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 [4]. 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 [1]. Also in angiogenesis, the maintenance of hematopoietic stem cells and bone formation [2]. In fact, changes in the partial pressure of oxygen can influence the function of osteoblasts and osteoclasts [3]. 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].