Revista de Osteoporosis y Metabolismo Mineral

Life expectancy has increased rapidly in the last century due to economic growth. This has led to reduced mortality, improved quality of life, as well as greater availability of health care. In fact, there are more elderly people than at any other time in our history, and it is anticipated that within the next few years there will be more older adults than children. This forecast makes it essential for people to reach this age in good health, to avoid increased healthcare costs due to longer hospital stays, readmissions and demand for healthcare resources. One of the most common disorders associated with aging is osteoporosis, the most fatal consequence of which is fracture. Approximately half of the clinical fractures that occur in postmenopausal women do not present criteria for osteoporosis according to their bone mineral density [1]. In fact, the highest percentage of fractures occur in osteopenic women. Thus, other variables or tools are needed that allow the identification of people at high risk of fractures, a determining factor of morbidity and mortality in the elderly population.

Aromatase inhibitors (AIs) are the recommended adjuvant therapy to treat estrogen receptor-positive breast cancer [1,2]. Its effectiveness in reducing the risk of recurrence and mortality is acknowledged [3]. However, AIs are also associated with various side effects that affect patients’ quality of life and therefore compromise adherence to treatment and associated mortality [4].
Reportedly, 30% of patients prescribed with AI discontinue their treatment due to adverse events [5], mainly musculoskeletal [6,7]. Among them, the most frequent are arthralgias [8] and accelerated loss of bone mass [9] associated with an increase in osteoporotic fracture [10,11]. To prevent the loss of bone mass, treating patients with antiresorptives is recommended, with bisphosphonates (BP) being the most used [12-14].
BP use has been associated with improved mortality associated with reduced bone metastases [13]. Similarly, a study published in a Korean population showed the use of BP was associated with improved adherence [15].

The generation of functional tissue through tissue engineering has a high impact in various areas of regenerative medicine, among which is skeletal tissue. The first implants were used in the field of medicine, in 1909, when Kirschner wires and Steinman nails were developed for the fixation of bone fractures, where stainless steel was used. Over the years, steel has been improved, making it more resistant to corrosion and not causing harmful effects on the human body. In 1940, the study of titanium (Ti) began as a biomaterial for bone implantation [1].
The phase change determines the change in the crystalline structure of the material when subjected to temperature changes. Titanium’s allotropic transformation occurs at 882ºC and goes from an α phase, which has a compact and hexagonal structure (HCP), little deformable and resistant at room temperature, to a β phase characterized by a cubic structure centered on the body (BCC), which is easily deformable and allows for carrying out heat treatments to optimize the material’s properties [2].

Pleitropin (PTN) is a cytokine secreted by multiple tissues during embryonic development, and which in adulthood is abundantly expressed in the brain and bone [1,2]. PTN is composed of 136 amino acids and its sequence is very rich in lysine and cysteine. Together with midkine (Mdk), with which it shares 50% homology, this cytokine constitutes the heparin-binding family of growth and differentiation factors, both having affinity for bone extracellular matrix [3-5]. PTN is also known as osteoblast stimulating factor 1 (OSF-1) or heparin-linked growth factor (HB-GAM) [6]. This cytokine was initially isolated from the bone and neuronal tissues of newborn rats [2,7,8] and subsequently its homologues have been found in many species including humans, with 90% homology between the different species [9,10].
PTN reportedly exerts its effects through its binding to glucosamin-glucans of several receptors such as N-syndecan, also called syndecan 3 [11], syndecans 1 and 4 [12], integrin αvβ3 [13] and the receptor protein tyrosine phosphatase beta/zeta (PTRPβ/ζ) [14]. It has also been suggested that nucleolin may be a low-affinity receptor for PTN [15] and that anaplastic lymphoma kinase (ALK) may play a role in PTN signaling [16].