The nucleus contains most of the genetic information, distributed throughout the approximately 3 billion nucleotides of human haploid DNA. The approximately 21,000 genes that encode the proteins necessary for the various organic functions are represented there, as well as an indeterminate number of genes that are transcribed into RNAs that do not encode proteins, but have regulatory functions[1].
Mitochondrial DNA is smaller, having about 16,000 nucleotides, with genes to encode 13 proteins and 24 non-coding RNAs (transfer and ribosomal)[2].
DNA changes that lead to disease can be classified according to various criteria, including:

Osteoporosis is a bone disease characterized by a decrease in bone mineral density (BMD) and an increased risk of fragility fractures. Osteoporotic fractures, particularly hip fractures, cause significant mortality and morbidity in men and lead to considerable social costs in this population, including direct medical costs and indirect costs resulting from reduced quality of life, disability and death[1].
Of all osteoporotic fractures, it is hip fractures that contribute to the highest morbidity and mortality in men. Each year about 80,000 men will have a hip fracture. Of these, one in three will die during the first year after this hip fracture and another third will fracture again[2]. However, there is a lack of awareness among healthcare professionals about the need to screen men for osteoporosis so that male osteoporosis remains largely underdiagnosed and untreated.

Conventionally, calcium, phosphorus, calcitriol and PTH were considered the only regulators of bone and mineral metabolism. In recent years, this axis of regulation has been complicated due to emergence of other factors with a crucial role in bone and mineral metabolism, such as fibroblast growth factor 23 (FGF-23) and the so-called klotho anti-aging protein.

Biological actions of FGF-23 and PTH
Biological action of FGF-23
FGF-23 is a 251 amino acid protein synthesized and secreted by bone cells, mainly osteoblast[1]. FGF-23 has been identified as the main regulatory factor of phosphorus metabolism, a critical element for maintaining skeletal integrity and for the development of multiple enzymatic processes[2]. In addition, in the last decade it has been attributed a notable role in the pathophysiology of vascular calcifications[3] and cardiovascular disease (CV), both in the general population[4-6] and in patients with chronic kidney disease[7].

Antiresorptive (or antiresorptive) drugs are the cornerstone of osteoporosis treatment. For decades, they have been considered the first step in treating this disease, although more recently some have been discontinued as indication. Others do not always have to be used as the first therapy in the current sequential treatments supported by the main scientific societies. There are five classes of purely antiresorptive drugs: bisphosphonates (BF), estrogen, selective estrogen receptor modulators (SERMs), calcitonin, and monoclonal antibodies against the activating receptor for nuclear factor κB ligand (RANKL) such as denosumab. For its part, a dual-action antiresorptive and osteoforming drug (strontium ranelate) was widely used from 2004 until its marketing cessation in 2017 in Europe for the reasons that will be detailed later. The treatments to be developed here are based on studies in postmenopausal women, although they can be extrapolated to men and to glucocorticoid-induced osteoporosis, although with less evidence[3].

Osteoporotic fractures, especially those of the hip, are one of the main causes of disability in the elderly population, triggering a considerable decrease of life quality and lifespan. Besides, more than 30% of people die during the first year after suffering one of these fractures[1]. In 2010, the European Union recorded nearly 3.5 million fragility-induced fractures that led to 43,000 deaths. From an economical point of view, these fractures meant an expenditure of 37 billion euros, a sum that is expected to rise by 52% in 2025[2].
Vitamin D and calcium are essential compounds for bone metabolism and prevention of osteoporotic fractures. Two recent meta-analyses have reported that low levels of 25(OH)D are related to the increase of fragility-induced fractures due to bone mass loss and bone structure deterioration[3,4].