Volume 12 · Number 4 · December 2020
- Comparison of the femur proximal extremity’s densitometric values in young and healthy study participants: left-handed vs. right-handed [115-121]
- Fracture risk predictors of a postmenopausal female population by binary statistical procedure CART [122-128]
- Evaluation of bone mineral density and 3D-Shaper parameters in congenital hypophosphatasia of the adult [129-134]
- Cx43 and primary cilium involvement in osteocyte activity [135-140]
- ¿Can a genetic condition be diagnosed based on phenotypic characteristics? A case of pseudo-hypoparathyroidism in Ecuador [141-145]
- Connexin 43 and cellular senescence: new therapeutic strategies for treating osteoarthritis [152-154]
This issue of the journal offers an interesting article on possible differences in femur densitometry related to the dominance of the upper extremities between left and right handed .
Dual-energy X-ray absorptiometry (DXA) is based on the measurement of areal bone mineral density centimeter (BMD, g/cm2) in the proximal femur and lumbar spine. Conditions such as osteoarthritis or osteophytic calcifications influence spinal BMD and confer a great value to femoral measurement. Since the DXA technique began being used on the hips, the presumption that there may be a minimal bilateral asymmetry between the proximal femurs has been maintained, but with no clinical relevance. Several research groups have studied this question. It has not been established whether there are systematic differences between the BMD of both hips, and in order to answer the questions: is the bone density in one of the femurs similar to same in the opposite side? which of them to choose?
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 .
¿Can a genetic condition be diagnosed based on phenotypic characteristics? A case of pseudo-hypoparathyroidism in Ecuador
Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders which share in common a parathyroid hormone resistance (PTH).
Globally, estimated prevalence is 0.79/100,000 , though it depends on the analysed type of PHP, and it oscillates between 6.7 and 3.3 cases per million inhabitants in Italy  and Japan  respectively. Between 2000 and 2019, 325 cases  have been described in worldwide literature, most of them in developed countries, in which in addition, PHP subtypes have been documented throughout genetic studies. 1a subtype is the most common, representing 70% of the cases . 47 cases have been reported in Latin America between 2000 and 2020 [5-10], the most frequent subtype being 1b, followed by 1a and 1c. Due to a lack of genetic studies, in some cases is not possible to precisely ascertain the belonging to one or another subtype .
Osteocalcin is a protein synthesized by the osteoblast. It was identified in the late 1970s and in humans contains 49 amino acids . Before being released into the extracellular matrix, osteocalcin undergoes gamma-carboxylation, as gamma-carboxy-glutamic acid binds at positions 17, 21 and 24. A gamma-carboxylase is involved in this reaction and the presence of vitamin K is required (Figure 1). The presence of the two carboxyl groups causes gamma-carboxylated osteocalcin to have a high affinity for calcium and, when released into the extracellular environment, binds in a large proportion to hydroxyapatite in bone. A part of this gamma-carboxylated osteocalcin and also non-carboxylated osteocalcin remain in the circulation . Only 10-30% of the synthesized osteocalcin reaches the circulation, and the rest remains attached to the bone matrix. Non-carboxylated osteocalcin represents 1/3 of total osteocalcin. During resorption, when the bone matrix is destroyed, part of the osteocalcin that is bound to the bone passes into the circulation . Osteocalcin is only synthesized by osteoblasts and is the most abundant non-collagenous protein in the extracellular matrix and is the tenth most abundant protein in vertebrates . Since first reported, its levels were correlated with bone formation . For all researchers working in bone metabolism, having a new bone formation marker was a breakthrough when the only markers of remodeling that were available up to that time were hydroxyproline and total alkaline phosphatase. The bone isoenzyme of alkaline phosphatase could also be measured by a rather complex method by electrophoresis. Osteocalcin has been used for many years as a marker of bone formation in practically all the work carried out in this regard. It is used less since 2011 when the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommended that the N-terminal propeptide of type I collagen (PINP) be used as a marker of formation and the C-terminal β-telopeptide of type I collagen or β-crosslaps (β-CTX) as a marker of resorption in clinical studies on osteoporosis .read more
Osteoarthritis (OA) is one of the most prevalent rheumatic diseases at present. It is characterized by the progressive degeneration of articular cartilage accompanied by alterations in other tissues, such as in the subchondral bone, synovial tissue or muscle. Currently one of the most frequent causes of disability in the aging population worldwide, OA is one of the main causes of chronic pain. From the biomechanical point of view, the joint is involved in maintaining mechanical support by stabilizing movement and flexion. The mechanical consequences of joint degeneration include the loss of stability or increased load stress on the joints, associated with changes in the structure and composition of the articular cartilage. Given that the molecular mechanisms by which joint tissue degradation and the loss of its homeostasis occur are not yet known, the current treatments available are based on the use of anti-inflammatories and pain relief drugs.read more
COVID-19 and vitamin D. Position paper of the Spanish Society for Bone Research and Mineral Metabolism (SEIOMM)
Vitamin D exerts its effect mainly through its active metabolite, 1,25-dihydroxycholecalciferol, by binding to a receptor with wide distribution in the different cells of the body. This receptor regulates the expression of genes involved in different biological functions, including organ development, cell cycle control, phosphocalcic metabolism, detoxification, and control of innate and adaptive immunity [1,2]. Regulation of the vitamin D receptor is determined by interacting environmental, genetic, and epigenetic factors.
Vitamin D increases intestinal absorption and tubular reabsorption of calcium, inhibiting PTH synthesis. This leads to a reduction in bone turnover, which helps maintain its strength and reduce the risk of fractures. In addition, it exerts an intraosseous effect, facilitating the mineralization of the matrix, which prevents the development of rickets in children and osteomalacia in adults. Numerous studies have been published showing an association between low levels of vitamin D and various chronic diseases, such as cancer, diabetes, cardiovascular diseases, multiple sclerosis, and infectious diseases, among others . These associations can be explained through different pathophysiological mechanisms related to vitamin D deficiency.