Hypercalcemia is a relatively common clinical problem and a frequent laboratory finding, both in hospital and out-of-hospital practice. Calcium ions play a critical role in many cellular functions. Parathyroid hormone (PTH) and vitamin D are the most important hormones for regulating calcium. The main sources of serum calcium are intestinal absorption, stimulated by active vitamin D metabolites, and bone resorption, usually stimulated by PTH. Therefore, hypercalcemia can be classified as PTH-dependent (due to increased secretion of PTH by the parathyroid glands) and independent of PTH. The latter cases are attributable to increased bone resorption and/or increased intestinal absorption of calcium, induced by factors other than PTH. Among them, PTH-related protein (PTHrP) and locally produced cytokines are factors that often cause hypercalcemia in cancer patients . Unregulated extrarenal synthesis of 1,25-dihydroxyvitamin D can also cause hypercalcemia, particularly in patients with chronic granulomatous disorders and in some patients with lymphoma .Read More
Category: Original Articles
Association of biochemical parameters of bone metabolism with progression and/or development of new aortic calcifications
Atherosclerosis, arteriosclerosis, vascular calcification and osteoporosis are common age-related disorders associated with high morbidity and mortality [1,2]. Due to the increased life expectancy in the Spanish population, these disorders are expected to become more and more frequent in the coming decades. Although recent work has been carried out on the development of non-invasive techniques for the early detection of vascular calcifications, such as pulse wave velocity and non-contrast carotid ultrasound, serum biochemical parameters continue to be the most widely used option for monitoring patients with bone metabolic disorders [3-5].Read More
Search for variants of the LRP4 gene in women with high bone mass and in patients with Chiari type I malformation
The Wnt signalling pathway is involved in a wide range of processes, including bone development and homeostasis . In accordance with this, mutations have been identified in various components of the Wnt pathway that cause different musculoskeletal diseases . The canonical Wnt pathway begins with the formation of a heterotrimeric complex between a co-receptor, LRP5/6, a ligand, WNT, and a receptor, FZD, which produces an accumulation of β-catenin that, once in the nucleus will activate the transcription of numerous important target genes for bone . This activation is finely regulated by a series of extracellular inhibitors such as DKK1 and sclerostin that bind to LRP5/6, preventing the formation of the heterotrimeric complex. For DKK1 and sclerostin to exert their inhibitory activity, they must form another heterotrimeric complex with LRP5 and KREMEN1/2 or LRP4, respectively. Although in the case of DKK1 the presence of KREMEN does not seem to be necessary to carry out a correct inhibition, the presence of LRP4 is essential for the inhibitory function of sclerostin [3,4].Read More
Proximal extremity fractures of the femur are a very common problem in today’s society and of great importance as there has been an increased incidence in the population. This increase is explained by the longer life expectancy in recent years, thus increasing the elderly population and, therefore, related diseases. This is particularly relevant in Spain which has, of late, seen a severe aging of the population .
Several epidemiological studies describe the incidence of hip fracture in Spain. In most cases these are local studies and carried out over short periods of time. National studies have been carried out, although to a lesser extent . According to the Ministry of Health and Social Policy’s 2010 report “Hip fracture care in the hospitals of the National Health System” , a total of 487,973 cases of fracture were recorded between 1997 and 2008. In these figures and in those carried out in various local studies2, a predominance of cases in the female sex and an increase in the incidence in age over the years has been found.
Comparison of the femur proximal extremity’s densitometric values in young and healthy study participants: left-handed vs. right-handed
Dual-energy X-ray absorptiometry, commonly known as bone densitometry , 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 . 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].Read More
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 . 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 . 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 . 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 . 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.
Evaluation of bone mineral density and 3D-Shaper parameters in congenital hypophosphatasia of the adult
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) . 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 . 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 . 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 .Read More
Bone tissue has the ability to adapt to surrounding environmental stimuli by altering its morphology and metabolism .
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 . 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 , parathyroid hormone receptor type 1 (PTH1R) ligands, connexins  and primary cilia. Some of these mechanosensors have been found to interact with each other, allowing the integration of multiple extracellular signals .
Effect of frailty and sarcopenia on the risk of falls and osteoporotic fractures in an unselected population
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 . 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.Read More
Persistence to aromatase inhibitors in the SIDIAP cohort: mortality and influence of bisphosphonates
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 . However, AIs are also associated with various side effects that affect patients’ quality of life and therefore compromise adherence to treatment and associated mortality .
Reportedly, 30% of patients prescribed with AI discontinue their treatment due to adverse events , mainly musculoskeletal [6,7]. Among them, the most frequent are arthralgias  and accelerated loss of bone mass  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 . Similarly, a study published in a Korean population showed the use of BP was associated with improved adherence .
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 .
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 .
Study of bone factor expression in murine model in the absence of pleiotrophin and its changes in the inflammatory situation
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) . 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 , syndecans 1 and 4 , integrin αvβ3  and the receptor protein tyrosine phosphatase beta/zeta (PTRPβ/ζ) . It has also been suggested that nucleolin may be a low-affinity receptor for PTN  and that anaplastic lymphoma kinase (ALK) may play a role in PTN signaling .
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