Mineral Disorders Research Articles

Clinical Utility of Bone Turnover Markers in Chronic Kidney Disease

Chronic kidney disease (CKD) often leads to mineral and bone disorders (CKD-MBDs), which are nearly universal in patients undergoing dialysis. CKD-MBD includes abnormal calcium-phosphate metabolism, vascular and soft tissue calcification, and bone abnormalities (renal osteodystrophy [ROD]). Bone fragility in CKD occurs due to low bone mass and poor bone quality, and patients with CKD have higher fracture and mortality rates. Bone histomorphometry is the gold standard for ROD diagnosis; however, it is labor-intensive and expensive. The Kidney Disease Improving Global Outcomes clinical practice guidelines on CKD-MBD suggest serum parathyroid hormone (PTH) and bone-specific alkaline phosphatase (bone ALP) for predicting bone turnover in ROD. In this review, we focus on the role of PTH and bone turnover markers, intact procollagen type N-terminal propeptide of type I collagen, bone ALP, and tartrate-resistant acid phosphatase 5b in diagnosing ROD, predicting fractures, and guiding treatment in patients with CKD.

Reduced resting and task-related alpha activity in mine workers: Implications for occupational health and neurodegenerative risk

Underground mine workers face many risk factors at work sites that are known to affect the neural system. Observational studies report that these risk factors precede neuromuscular and neurodegenerative disorders, especially in old-age miners. Neurodegenerative disorders have electrophysiological, anatomical, and functional changes long before symptoms are seen in older adults. Therefore, this study investigated whether risks faced by miners at young ages were reflected in electrophysiological signals. Twenty-one underground miners and twenty-two above-ground workers matched with them in terms of age, education, and working duration were included in this study. Participants were recorded with a 20-channel EEG during the resting-state (eyes open and closed; EO-EC) and the perception of the International Affective Picture System Paradigm (IAPS). Time-frequency analyses were performed for alpha frequency. Rs-EEG results showed a statistically significant difference in alpha power between the EO and EC states in the control group. However, there was no statistical difference in alpha power between these two conditions in the miners. Additionally, we noted a more pronounced decrease in alpha responses in the posterior region during EC in the miners. The group's main effects were statistically significant in event-related alpha responses during emotional responses. Accordingly, event-related alpha responses of the miner group were lower than the control group in terms of both power spectrum and phase-locking. Underground mine workers are cognitively and emotionally affected by risks in the work environment. Electrophysiological changes seen in young underground workers may be a harbinger of neurodegenerative disorders in miners' old age. Our research findings may lead to the development of occupational neuroscience, social policies, and worker health, which are necessary to improve working conditions for mineworkers.

Study of bone mineral disorders in hemodialysis patients at Hue Central Hospital

Study of bone mineral disorders in hemodialysis patients at Hue Central Hospital

Vitamin D Status in Supplemented Hemodialysis Patients

Introduction: Chronic kidney disease (CKD) causes decreased activity of the enzyme 1-alpha-hydroxylase and calcitriol deficiency with mineral and bone metabolism disorders or secondary hyperparathyroidism. Anticipation of the occurrence of these complications implies the systematic supplementation of all hemodialysis patients, with monitoring of biological parameters. It is in this context that this study was carried out, the general objective of which was to establish the profile of vitamin D concentration in hemodialysis and Ivorian public sector supplemented patients in Abidjan. Patients and Methods: In a cross-sectional study conducted from September to December 2022, we included 89 patients with end-stage CKD treated with hemodialysis at the CNPTIR in Cocody. The collection of epidemio-clinical data was done on the basis of a questionnaire on the one hand and the patients' medical records on the other. The vitamin D concentration was determined by the ELFA immunoassay method on mini Vidas (BIOMERIEUX). Results: The mean age of the patients was 45 ± 13 and 65.17% of them were men. 55.06% of the patients had been treated with dialysis for at least 5 years. 48.31% of the patients had regular supplementation treatment. Of the two types of vitamin D supplementation, 94.38% of the study population was supplemented with cholecalciferol compared to 18% for alfacalcidol with 12% of patients included, using both types. From a biological point of view, it appears that the average concentration of vitamin D in the patients was 26.9 ng/mL, and only 16% have a concentration of less than 20 mg/mL, corresponding to an deficiency vitamin D status. Conclusion: At the end of this cross-sectional study, it emerged that the average in adult hemodialysis subjects followed at the CNPTIR in Cocody had an insufficient vitamin D status. And 37% of the study population with normal vitamin D status. However, these results could be improved by better accessibility to the products, and regular compliance with supplementation.

Associations of Cognitive Function with Serum Magnesium and Phosphate in Hemodialysis Patients: A Cross-Sectional Analysis of the Osaka Dialysis Complication Study (ODCS).

Cognitive impairment and dementia are common in patients with chronic kidney disease, including those undergoing hemodialysis. Since magnesium and phosphate play important roles in brain function and aging, alterations in these and other factors related to bone mineral disorder (MBD) may contribute to low cognitive performance in patients on hemodialysis. This cross-sectional study examined the associations between cognitive function and MBD-related factors among 1207 patients on maintenance hemodialysis. Cognitive function was assessed by the Modified Mini-Mental State examination (3MS). The exposure variables of interest were serum magnesium, phosphate, calcium, calcium-phosphate product, intact parathyroid hormone, fetuin-A, T50 calciprotein crystallization test, use of phosphate binders, use of cinacalcet, and use of vitamin D receptor activators. Multivariable-adjusted linear regression models were used to examine the associations between 3MS and each of the exposure variables independent of 13 potential non-mineral confounders. We found that lower 3MS was associated with lower serum magnesium, lower phosphate, lower calcium-phosphate product, and nonuse of phosphate binders. These results suggest that magnesium and phosphate play potentially protective roles against cognitive impairment in this population.

Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease

BackgroundCarotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)—the earliest detectable serum abnormality associated with CKD-MBD—has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD.MethodsA cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored.ResultsWe recruited 42 children aged 2–18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05).ConclusionsFGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.

Adiposity and Mineral Balance in Chronic Kidney Disease.

Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD. BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.

Evaluation of the impact of specific oral health parameters on the quality of life in children with rare disorders of phosphorus-calcium metabolism

Relevance. Understanding the impact of oral health problems on the quality of life in children with rare metabolic disorders that affect mineral metabolism is critically important.Materials and methods. An oral health assessment was conducted on 59 children aged 6 to 17 years with rare diseases affecting mineral metabolism, each with a genetically confirmed diagnosis. The children were divided into two study groups: the first group (24 children) comprised those with bone mineralization disorders (hypophosphatemic rickets, hypophosphatasia), while the second group (35 children) included those with disorders of bone and cartilage formation (osteogenesis imperfecta, Marfan syndrome, achondroplasia, etc.). The clinical condition of the children's dental tissues was assessed by evaluating oral hygiene levels and caries intensity in permanent teeth, using the OHI-S and DMFT indices, respectively. The pufa/PUFA index was used to document complications arising from dental caries. To assess the perception of oral health problems, a survey was administered to parents and legal guardians using the Oral Health-Related Quality of Life (OHRQoL) questionnaire.Results. The average DMFT and OHI-S index values did not show statistically significant differences, with values of 4.26 ± 0.28 and 1.96 ± 0.15 in the first group, and 3.76 ± 0.40 and 1.75 ± 0.10 in the second group, respectively. However, the mean pufa/PUFA index values were significantly higher in children with bone and cartilage formation disorders (p = 0.003), being three times greater than those in the group with bone mineralization disorders, with values of 1.03 ± 0.18 and 0.30 ± 0.11, respectively. This increase was associated with higher correlation coefficients between the DMFT and PUFA indices and the modules for physical discomfort, oral functional status, and emotional well-being, with values of 0.38 and 0.41, and 0.49 and 0.27, compared to 0.07 and 0.02, and 0.29 and -0.21 in the first group. These differences were statistically significant at p &lt; 0.05 and p &lt; 0.005.Conclusion. The study revealed that existing oral health conditions have the greatest impact on the quality of life in children with rare diseases affecting bone and cartilage formation.

8620 Prevalence of Osteopenia of Prematurity and Risk Factors in Neonatal of Maternity Hospital

Abstract Disclosure: D.M. Bastos: None. J.G. Bastos: None. A.C. Bastos: None. Introduction: The osteometabolic disease of prematurity (ODP), formerly known as osteopenia of prematurity, corresponds to a disorder of bone mineralization in the neonatal period in very low birth weight premature newborns. The estimated prevalence is about 30% when the birth weight is less than 1,500 grams and around 60% when it is less than 1,000 grams. There is no specific clinical picture, and it can present with mild manifestations, growth deficit, or even evolve with severe rickets and fractures. To qualify the care of premature newborns (NB) in our Service, we question what is the local prevalence of ODP and what are the clinical, biochemical, or imaging risk factors that are potentially related to a greater predisposition to this condition. Objective: Evaluate the prevalence of ODP and recognize potential risk factors in NBs in a neonatal ICU of a reference maternity hospital in Curitiba/ PR. Method: Retrospective longitudinal study, with analysis of medical records of patients born with a gestational age less than 34 weeks and birth weight less than 1,500 grams, born between January/2013 to August/2016. Discussion: Prematurity is the significant factor, followed by low birth weight, for osteopenia. Newborns (NB) with a birth weight below 1500g should receive 40mg/Kg of calcium and 50 mg/Kg of phosphorus. Supplementation of human milk should be started from 15 days of life or when oral intake reaches 100ml/Kg per day (1g/20 ml of milk). In this study, the classification of the growth curve and prevalence by sex were divergent with the literature. The most vulnerable are those with parenteral nutrition or prolonged fasting, as the adequate diet is the basis of prevention and treatment, similar data being found, as well as association with prolonged use of diuretic, presence of sepsis diagnosis and bronchopulmonary dysplasia. However, there is still a lack of specific and sensitive markers for early diagnosis and treatment. Conclusion: The prevalence of Osteopenia of Prematurity was lower than that found in the literature. The risk factors bronchopulmonary dysplasia and use of diuretics were statistically significant when evaluated in patients with osteopenia. However, no relationship was found between ODP and sepsis, as well as a relationship between ODP and Necrotizing Enterocolitis. Regarding the days kept fasting, use of TPN and Use of antibiotics, a longer duration of use was obtained when compared with the group that did not develop the disease. Presentation: 6/3/2024

Vitamin D Deficiency in Hemodialysis Patients and Cardiovascular Diseases Risk

Abstract Background Dialysis patients experience an excess mortality, predominantly of sudden cardiac death (SCD). Vitamin D deficiency is present in the vast majority of patients with chronic kidney disease (CKD), and correcting a poor vitamin D status is recommended as a treatment of CKD–mineral and bone disorders. Accumulating evidence suggests a role of vitamin D for myocardial and overall health. Aim of the Work To assess the correlation between vitamin D status and cardiovascular outcomes in prevalent hemodialysis patients. Subjects and Methods This was prospective interventional study, conducted Abo elnomros hemodialysis unit, on 50 prevalent HD patients. All patients were subjected to the following: Demographic data, laboratory investigations during the last 6 months, Echo-cardiogram before the study and after 6 months. Results The mean Ca was 7.94(±0.77 SD), the mean Po4 was 4.8(±0.8 SD), the mean PTH was 381(±127 SD), the mean vitamin D was 11.4(±1.5 SD). Conclusion High prevalence of vit D deficiency in dialysis patients, and showed a significant association between 25-OH vitamin D analogues supplementation and decrease cardio-vascular risk.

Association between Serum Zinc and All-Cause Mortality in Patients Undergoing Maintenance Hemodialysis: The Osaka Dialysis Complication Study (ODCS).

Zinc is an essential microelement, and its deficiency is common in patients undergoing hemodialysis. However, the association between serum zinc and mortality in these patients remains unclear. The aim of this study was to explore the possible association between serum zinc levels and all-cause mortality in prevalent patients with kidney failure on maintenance hemodialysis. This was a prospective cohort study of maintenance hemodialysis patients followed up for 5 years. The key exposure was serum zinc level measured at baseline, and the outcome was all-cause mortality. Their association was analyzed using Cox proportional hazard models. Among 1662 eligible patients selected for this analysis, 468 (28%) died. Lower serum zinc levels were associated with a higher risk for mortality, independent of the major demographic factors and factors including mineral and bone disorder and renal anemia. However, this association was no longer significant when adjusted for serum albumin. Because there was a close correlation between serum zinc and albumin levels, we performed further analyses in which participants were categorized into four groups by median serum zinc (68 µg/dL) and albumin (3.7 g/dL) levels. In the lower serum albumin groups, risk of death was significantly higher in those with lower zinc than those with higher zinc levels, whereas such a difference was not significant in the high serum albumin groups. In patients undergoing maintenance hemodialysis with lower serum albumin levels, a lower serum zinc level was associated with a higher risk of mortality.

Multidisciplinary team approach for CKD-associated osteoporosis.

Chronic kidney disease mineral and bone disorder (CKD-MBD) contributes substantially to the burden of cardiovascular disease and fractures in patients with CKD. An increasing arsenal of diagnostic tools, including bone turnover markers and bone imaging, is available to support clinicians in the management of CKD-associated osteoporosis. Although not mandatory, a bone biopsy remains useful in the diagnostic workup of complex cases. In this special report, the European Renal Osteodystrophy (EUROD) initiative introduces the concept of a kidney-bone multidisciplinary team (MDT) for the diagnosis and clinical management of challenging cases of CKD-associated osteoporosis. In 2021, the EUROD initiative launched virtual clinical-pathological case-conferences to discuss challenging cases of patients with CKD-associated osteoporosis, in whom a bone biopsy was useful in the diagnostic workup. Out of these, we selected 4 representative cases and asked a kidney-bone MDT consisting of a nephrologist, an endocrinologist and a rheumatologist to provide comments on the diagnostic and therapeutic choices. These cases covered a broad spectrum of CKD-associated osteoporosis, including bone fracture in CKDG5D, post-transplant bone disease, disturbed bone mineralization, severely suppressed bone turnover, and severe hyperparathyroidism. Comments from the MDT were, in most cases, complementary to each other and additive to the presented approach in the cases. The MDT approach may thus set the stage for improved diagnostics and tailored therapies in the field of CKD-associated osteoporosis. We demonstrate the clinical utility of a kidney-bone MDT for the management of patients with CKD-MBD and recommend their establishment at local, national, and international levels.

Effects of hemodialysis adequacy on chronic kidney disease complications using latent class trajectory modeling: a real-world study based on long-term observation of Kt/V.

Previous studies on hemodialysis adequacy primarily focused on the association between Kt/V and survival, and low Kt/V is associated with increased mortality. There is a paucity of research on the correlation between Kt/V and chronic kidney disease (CKD) complications. The retrospective study was conducted in the blood purification center of a tertiary hospital in China from July 2020 to September 2022. It aimed to analyze the association between latent Kt/V trajectory categories and CKD complications (hypertension, anemia, mineral and bone disorder) and inflammatory markers. The latent class trajectory model was established to describe the different patterns of Kt/V changes over the observation period. During the 2-year study period, 93 patients on thrice-weekly hemodialysis with residual kidney function <2 mL/min were included. In the 3-class Kt/V trajectory model, 21 patients were in class 1 with a Kt/V trajectory that declined from a higher to lower levels (from >1.6 to <1.4), 59 patients were in class 2 with Kt/V consistently in a relatively low range (around 1.4), and 13 patients were in class 3 with Kt/V stabilized around 1.6. No significant difference in CKD complications or inflammation markers was observed among the three Kt/V trajectories. Under the premise of adequate Kt/V, neither a stable higher Kt/V nor a declined Kt/V significantly influenced CKD complications or inflammatory markers.

Study on the evaluation of shale reservoir brittleness based on mineral disorder

Brittleness serves as a critical indicator for assessing whether reservoirs can form complex fracture networks. While methods based on brittle mineral content or rock mechanical parameters are widely used, their lack of integration between mineralogy and mechanics introduces limitations. A single evaluation parameter cannot accurately assess shale brittleness. There is a need for a universally applicable method that comprehensively considers mineral composition, mechanical properties, and brittleness variations in shale evaluation. This study uses Longmaxi shale in the Sichuan Basin as an example, establishing a mineral disorder index based on shale mineral composition and mechanical characteristics, incorporating the influence of confining pressure to establish a shale brittleness index. Results indicate varying weights of brittleness contributions from different minerals, ranked in descending order: pyrite, quartz, calcite, dolomite, feldspar, and clay. Greater complexity in mineral combinations correlates with lower shale brittleness indices. Typically, single mineral disorder indices show a positive correlation with internal mineral disorder indices. Confining pressure exhibits an inversely proportional relationship with shale brittleness indices, with brittleness at 30, 50, and 70 MPa confining pressures being 0.737, 0.586, and 0.451 times those without confining pressure, respectively. This method guides current brittleness research and reservoir production enhancement.

Etiopathogenetic features of bone metabolism in patients with diabetes mellitus and Charcot foot

Diabetic neuropathy is one of the most common diabetes mellitus complications associated with mediocalcinosis of the lower extremities, a significant decrease in feet bone mineral density, and a high incidence of cardiovascular disease. In most cases, calcium-phosphorus metabolism changes occur in patients with diabetic neuroarthropathy, or Charcot foot, when we can observe feet local osteoporosis, which in 90% of cases associated with a vessel's calcification of the lower extremities in the majority of diabetes population. A large number of studies presented literature have demonstrated that patients with Charcot foot can have accelerated bone metabolism and increased bone resorption. Patients with Charcot foot often have crucial abnormalities in the calcium-phosphorus parameters, bone metabolism, and levels of vitamin D and its metabolites. In addition, the duration of diabetes mellitus, the degree of its compensation widely affects the development of its micro- and macrovascular complications, which could also accelerate the development of mineral and bone disorders in these types of patients. Multifactorial pathogenesis of these disorders complicates the management of patients with a long and complicated course of diabetes mellitus. This review discusses the peculiarities of vitamin D metabolism, the importance of timely diagnosis in phosphorus-calcium disorders, and the specifics of therapy in these patients. Special attention is paid to the timely diagnosis of the Charcot's foots acute stage based on the bone marrow edema by MRI evaluation and the possibility of reducing the immobilization period.

Low-Protein Diets, Malnutrition, and Bone Metabolism in Chronic Kidney Disease.

Chronic kidney disease (CKD) has a high prevalence worldwide, with increasing incidence in low- and middle-income countries, and is associated with high morbidity and mortality, particularly from cardiovascular disease. Protein-restricted diets are one of the most widely used non-pharmacological approaches to slow the progression of CKD and prevent associated metabolic abnormalities. However, some concerns have been raised about the long-term safety of these diets, particularly with regard to patients' nutritional status and bone and mineral disorders. Therefore, the aim of this article is to review the most recent scientific evidence on the relevance of using protein-restricted diets (with or without keto-analogue supplementation) and, in particular, their relationships with malnutrition and mineral and bone disorders in people with CKD without kidney replacement therapies. Although protein-restricted diets, especially when supplemented with keto-analogues and highly personalized and monitored, do not appear to be associated with malnutrition, research on their effects on bone and mineral disorders is scarce, deserving further investigation.

Unraveling the Mechanisms of Magnesium Supplementation in Alleviating Chronic Kidney Disease Complications and Progression: Balancing Risks and Benefits.

Chronic kidney disease (CKD) is a major cause of death and disability worldwide. It is usually diagnosed at early levels because of its slow progression. Treatment should consider CKD complications (such as electrolyte level imbalance, vascular calcification, and bone mineral disorders), as well as the development of CKD itself. Large-scale studies have shown that current treatment guidelines are nearly ineffective and fail to achieve treatment goals. Guidelines have not paid as much attention to magnesium (Mg) as the other electrolytes, while Mg has a significant role in the treatment goals of CKD. Hypomagnesemia is the only electrolyte imbalance that is equally prevalent in all stages of CKD. A lower plasma Mg level in each stage of CKD is associated with a higher risk of CKD progression and cardiac events. Magnesium exerts its effects both directly and via other ions. Mg supplementation increases insulin sensitivity while reducing proteinuria and inflammation. It lowers blood pressure and inhibits vascular calcification primarily because of its effects on calcium and phosphate, respectively. Vitamin D supplementation for low-active vitamin D in CKD patients increases vascular calcification and cardiac events, but magnesium supplementation enhances vitamin D levels and activity without increasing the risk of cardiac events. However, careful attention is required due to the potential threats of hypermagnesemia, particularly in advanced CKD stages. Starting magnesium supplementation early in patients' treatment plans will result in fewer side effects and more advantages. More original research is needed to determine its optimal dose and serum levels.

Eduardo Slatopolsky: A Pioneer in the Field of Mineral and Bone Disorders in Kidney Disease.

Eduardo Alberto Slatopolsky (1934-2024), Washington University Joseph Friedman Professor Emeritus of Medicine, a prominent physician-scientist, was born in Buenos Aires, Argentina. The impact of his research in the area of mineral and bone disorders in kidney disease has been profound for over 50 years starting in the 1960s. He was a global authority on secondary hyperparathyroidism. He was instrumental in illustrating the role of hyperphosphatemia in chronic kidney disease (CKD) and in developing the first reliable parathyroid hormone (PTH) assay. His research led to the utilization of calcium salts as phosphate binders replacing the toxic aluminum salts. Moreover, he illustrated the role of vascular calcifications in CKD patients, paving the way for non-calcium phosphate binders. He proposed the use of calcitriol and later vitamin D analogs in the management of secondary hyperparathyroidism, which is the current standard of care. He demonstrated the decreased expression of the calcium-sensing receptor in parathyroid tissue in CKD patients. Dr. Slatopolsky's global legacy will last for generations.

Human genetic diseases of phosphate and pyrophosphate metabolism

In humans, physiological bone and tooth mineralization is a complex cell-mediated process. Prerequisites for proper mineralization include sufficient amounts of minerals (calcium and phosphate [Pi]) to initiate the formation and the growth of apatite crystals and adequate amounts of mineralization inhibitors, such as pyrophosphate (PPi), to prevent uncontrolled extraskeletal mineralization.In this review, we provide an overview of the genetics of human disorders of mineralization, focusing on Pi and PPi metabolism and transport diseases, as the Pi/PPi ratio is an important determinant of crystal production in vivo. Variants in genes implicated in the homeostasis of this ratio may lead to a systemic or local increased Pi/PPi ratio, either by increasing the Pi concentration or by decreasing the PPi concentration, resulting in ectopic calcifications; conversely, variants may lead to a decreased Pi/PPi ratio, resulting in defective mineralization.Owing to the implication of common pathways and, occasionally, to some extent of clinical overlap, an accurate diagnosis and understanding of the pathophysiology of these disorders may be challenging. However, precise molecular characterization of these conditions not only facilitates their diagnosis, but also helps to gather evidence regarding the pathophysiology and phenotype–genotype correlation to improve medical care and develop innovative therapeutics.

Biology of bone mineralization and ectopic calcifications: the same actors for different plays

Bone has several crucial functions. It is essential for locomotion and allows our body to stand erect against gravity. A mismatch between the mechanical stresses applied to it and its mechanical resistance leads to fractures. Bone also has numerous endocrine functions. It acts as a reservoir for minerals such as calcium and phosphorus, making it the target of calciotropic hormones that mobilize these minerals, particularly calcium, according to the body's needs. Additionally, bone secretes hormones, notably fibroblast growth factor 23 (FGF23), which regulates urinary excretion of phosphate and the bioavailability of active vitamin D. Bone mineralization is the process that facilitates the organized deposition of minerals in the bone matrix, providing rigidity and appropriate mechanical resistance. This process is compromised in genetically related bone mineralization disorders, such as those causing hypophosphatemia or hypophosphatasia. Conversely, calcification can be pathological, affecting soft tissues like the blood vessels, as seen in generalized arterial calcification of infancy (GACI) or arterial calcification due to CD73 deficiency (ACDC). The aim of this article is to first present the composition and structure of the mineralized bone matrix, to review the current understanding of the molecular mechanisms of mineralization, and finally to discuss the conditions associated with ectopic calcification and the underlying mechanisms.