Dual-energy X-ray absorptiometry, commonly known as bone densitometry [1], is a technic broadly used in daily clinical practice and is considered the gold standard to estimate the bone mineral density (BMD) [1-4]. When performing a densitometry, the values obtained, usually in the lumbar spine and in the proximal extremity of the femur, are compared with the reference values for the population of each country, so the T-score and Z-score values can be calculated [3-5]. By consensus, the World Health Organization recommended the osteoporosis densitometric diagnosis to be carried out in the presence of a T-score value lower than -2.5 of the typical deviation of the peak BMD [2]. Although this criterion has been a topic for controversy, it has also become a world reference that has allowed the homogenisation of the randomized trials, among other advantages [1-6].

The osteoporosis is an illness linked to a high morbimortality that increases as the population grows older. It has been defined as a systemic skeletal disease characterized by a deterioration of bone micro-architecture and a decrease of bone tissue, with a consequent increase in bone fragility and a higher susceptibility to fracture [1]. It is a clinically silent disease that is not manifested by other signs but for its complications, fractures.
The main consequences of osteoporosis are fragility fractures that can appear in different locations, though they typically happen on the vertebrae, distal radius and proximal extremity of the femur [2,3]. They are fractures with a high economic cost and are associated with a higher morbimortality, specifically those on the vertebrae and the proximal femur. Hip fracture mortality, the most serious manifestation of osteoporosis, is 8% during the first month after the fracture (acute mortality). It rises to 30% after a year [4]. Furthermore, the recovery of patients who do not pass away is poor. Only 30% of patients suffering a hip fracture return to the baseline situation [5]. The vertebral fracture shows a higher incidence than the hip fracture. While the hip fracture shows a yearly incidence of 1.3-1.9 cases/1,000 inhabitants/year, the incidence of vertebral fractures is 13.6/1,000 inhabitants/year in males and 29.3/1,000 inhabitants/year in females [2]. Although its mortality is lower than that of hip fracture, it is not despicable, especially in patients also presenting a respiratory disease [6,7]. Therefore treatments are designed to prevent its appearance through adequate therapeutic measures. In order to establish the most appropriate treatment it is necessary to dispose of stand-alone diagnostic factors that help identify the every patient’s individual risk through additional tests or risk scales.

Hypophosphatasia (HPP) is a rare metabolic disease characterized by low enzymatic activity of non-tissue-specific alkaline phosphatase (TNSALP), which causes an accumulation of its natural substrates: inorganic pyrophosphate (PPi), pyridoxal-5′-phosphate (PLP) and phosphoethanolamine (PEA) [1]. PPi acts as a potent inhibitor of hydroxyapatite crystal formation and its high extracellular levels can induce skeletal alterations, such as decreased bone mineralization [2,3]. In general, the more severe forms are associated with earlier symptoms and diagnosis, even perinatal, while the milder forms often present later in childhood or adulthood [4]. The importance of an early diagnosis lies in the potential severity of the disease and the alteration of the quality of life, as well as in the possible iatrogenesis derived from a wrong diagnosis and treatment [5]. Previous studies have analyzed the symptoms that characterize adult HPP, which usually shows a wide range of clinical manifestations, sometimes nonspecific, such as the presence of musculoskeletal pain, weakness, dental pathology or early loss of teeth, and the presence of of recurrent stress fractures and pseudofractures [6,7]. In a pediatric age cohort, the analysis of bone mineral density (BMD) in these patients has detected low values in the most severe cases [8].

Bone tissue has the ability to adapt to surrounding environmental stimuli by altering its morphology and metabolism [1].
The development, remodelling and repair of this tissue are dynamic processes, regulated by the joint activity of bone cells (osteocytes, osteoblasts and osteoclasts). Osteocytes are the most abundant type of cells in the bone. They are located in the mineralized bone matrix, forming a large cellular intercommunication network, called osteocyte lacuno-canalicular system (OLCS). Osteocytes are the main mechanosensory cells in the bone [2]. They can detect mechanical stimuli in the environment and communicate this signal to effector cells (osteoblasts and osteoclasts) and have different mechanosensory structures: ion channels, integrins [3], parathyroid hormone receptor type 1 (PTH1R) ligands, connexins [4] and primary cilia. Some of these mechanosensors have been found to interact with each other, allowing the integration of multiple extracellular signals [3].