Calcified Tissue International最新文献

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome caused by a mesenchymal tumor secreting a phosphaturic hormone called FGF23. Patients present with bone pain, fragility fractures and muscle weakness. Biochemical results show hypophosphatemia, raised serum alkaline phosphatase and reduced calcitriol. We report the case of a 44-year-old man who presented to the Emergency Departement with acute low back pain revealing extensive subchondral fractures between D2 and L5. Investigations showed partial Fanconi syndrome; nevertheless, he had profound hypophosphatemia, low 1,25-OH vitamin D and raised FGF23 levels suggesting a diagnosis of tumor-induced osteomalacia. A subcutaneous lesion was identified in the left leg on a PET-CT initially performed to rule out malignancy in the context of Fanconi syndrome. Tumorectomy enabled complete resolution of the electrolyte disturbances within days of surgery. This case shows that TIO may present as partial Fanconi syndrome, highlighting the importance of testing other electrolytes in cases of hypophosphatemia and the need to look for TIO in cases of partial Fanconi with severe hypophosphatemia.

Sport participation affects body composition and bone health, but the association between sport, body composition, and bone health in female athletes is complex. We compared areal bone mineral density (aBMD, DXA) and tibial volumetric bone mineral density (vBMD), geometry, microarchitecture, and estimated strength (HR-pQCT) in cross-country runners (n = 22), gymnasts (n = 23) and lacrosse players (n = 35), and investigated associations of total body lean mass (TBLM), team, and their interaction with tibial bone outcomes. Total body (TB), total hip (TH), femoral neck (FN), and lumbar spine (LS) aBMD were higher in gymnasts than runners (p < 0.001); FN and LS aBMD were higher in gymnasts than lacrosse players (p ≤ 0.045); and TB, TH, FN, and LS aBMD were higher in lacrosse players than runners (p ≤ 0.013). At the distal tibial metaphysis, total area (Tt.Ar) was higher in gymnasts than runners (p = 0.004); cortical area and thickness (Ct.Ar, Ct.Th) were higher in lacrosse players than runners (p ≤ 0.044); trabecular separation (Tb.Sp) was higher in runners than gymnasts (p = 0.031); and failure load was higher in both gymnasts and lacrosse players than runners (p ≤ 0.012). At the tibial diaphysis, Tt.Ar, Ct.Ar, cortical perimeter (Ct.Pm), and failure load were higher in gymnasts than runners (p ≤ 0.040). In multiple linear regression analyses, TBLM was significantly associated with metaphyseal failure load (ß = 0.30, p = 0.042), and diaphyseal Tt.Ar and Ct.Pm (ß = 6.17, p = 0.003; ß = 0.59, p = 0.010). Bone health can vary among different sport types and is associated with TBLM, which may be a modifiable factor to maintain or improve bone health.

X-linked hypophosphatemia (XLH) is a rare metabolic disorder characterized by elevated FGF23 and chronic hypophosphatemia, leading to impaired skeletal mineralization and enthesopathies that are associated with pain, stiffness, and diminished quality of life. The natural history of enthesopathies in XLH remains poorly defined, partly due to absence of a sensitive quantitative tool for assessment and monitoring. This study investigates the utility of 18F-NaF PET/CT scans in characterizing enthesopathies in XLH subjects. In 19 adult XLH subjects, enthesopathy burden was assessed by quantifying calcified sites on CT and 18F-NaF PET uptake at 16 common tendon/ligament insertion locations. Parameters obtained were (1) number of enthesopathy sites, (2) characterization of each site as CT-positive (CT +) and/or PET-positive (PET +), (3) a semiquantitative score based on severity of affected enthesopathies (CT-score_global and PET-score_global). Biochemical and self-reported questionnaires results were correlated with 18F-NaF PET/CT parameters. 18F-NaF PET/CT detected at least one enthesopathy in all subjects, with 18F-NaF PET positivity often detected before CT (19.4% of all enthesopathies). Age negatively correlated with the number of PET + /CT- enthesopathies and positively with PET-/CT + enthesopathies. PET-score_global was positively associated with ALP. While PET-score_global showed no correlation with any applied survey, CT-score_global was associated with worse functionality and pain. These associations suggest a progression from an actively mineralizing lesion to a more established, inactive lesion. Overall, although 18F-NaF PET/CT is not yet indicated for routine clinical use, it is a promising research tool for evaluating enthesopathy burden in XLH, offering valuable insights into the disease's progression and potentially enabling early therapeutic assessment.

Bone mechanical function is determined by multiple factors, some of which are still being elucidated. Here, we present a multivariate analysis of the role of bone tissue composition in the proximal femur stiffness of cadaver bones (n = 12, age 44-93). Stiffness was assessed by testing under loading conditions simulating a sideways fall onto the hip. Compositional properties of cortical and trabecular tissues were quantified in femoral neck cross sections by Fourier transform infrared (FTIR) spectroscopy and near infrared (NIR) spectroscopy. In addition, cross-sectional areas and cortical thickness and tissue mineral density (TMD) were measured at the femoral neck. Pearson correlation analysis showed a significant (p < 0.05) negative relationship between bone stiffness and cortical and trabecular water content, both total (r = -0.63) and tightly bound to matrix and mineral (r = -55). Additionally, significant (p < 0.05) positive correlations were found between stiffness and bone area, both total (r = 0.67) and trabecular (r = 0.58). However, linear regression using each of these properties to predict bone stiffness resulted in weak models (R² = 0.36-0.48). Interestingly, we found markedly stronger models (cross-validated R² = 0.80-0.92) by using partial least squares (PLS) regression to predict stiffness based on combinations of bone properties. The models with highest R² values were found when including bone water parameters as explanatory variables, both total and tightly bound, in cortical and trabecular. This study provides new insights by revealing a multifactorial relationship in which higher bone water content across different tissue compartments contributes to lower bone stiffness, highlighting bone water as a potential biomarker of bone quality and proximal femur mechanical function.

Rare bone diseases are clinically and genetically heterogenous. Despite those differences, the underlying pathophysiology is not infrequently different. Several of these diseases are characterized by abnormal bone metabolism and turnover with subsequent abnormalities in markers of bone turnover, rendering them useful adjuncts in the diagnostic process. As most rare bone diseases are inherited, genetic testing for implicated pathogenic variants, where known, is another relevant tool that can aid in diagnosis. While some skeletal disorders can be localized or monostotic, others can involve multiple skeletal sites and warrant imaging tools to localize them and determine the severity of disease and/or presence of complications as well as to assess bone quality and the potential risk of fractures. Rare bone disorders pose a great challenge in their diagnosis, ultimately resulting in delayed diagnosis, higher risk of complications and a poor quality of life in affected individuals. In this review we discuss the biochemical and radiological tools that can be utilized to diagnose selected orphan bone disorders, the clinical utility and limitations of these diagnostic tools, and areas where future research is warranted.

Gaucher disease is a rare lysosomal storage disorder characterized by the accumulation of glucocerebroside lipids within multiple organs due to a deficiency of the lysosomal enzyme (acid β-glucosidase). It is an inherited autosomal recessive disease. The onset of symptoms can vary depending on disease type and severity, with milder forms presenting in adulthood. The main clinical manifestations include cytopenia, splenomegaly, hepatomegaly, and bone lesions. GD is characterized by several bone manifestations, such as osteopenia/osteoporosis, focal lytic or sclerotic lesions, osteonecrosis acute or chronic bone pain, Erlenmeyer flask deformity, and subchondral joint collapse with secondary degenerative arthritis. In 70-100% of patients affected by Gaucher disease type 1, clinical or radiographic evidence of bone disease occurs. Among bone complications, osteoporosis is very common, but its etiopathogenesis in GD is not completely clear. Results deriving from experimental studies support the hypothesis that there is an aberrant activity of both osteoclasts and osteoblasts due to several factors, resulting in impaired bone turnover. Bone complications represent the main cause of pain, disability, and reduced quality of life in these patients. Therefore, there is a need to enhance awareness among physicians on the skeletal manifestations throughout life of GD patients, in order to improve diagnosis and management of bone complications. In particular, this narrative review focuses on risk of bone fragility in GD, etiopathogenetic hypotheses, epidemiological data, diagnosis, monitoring, and treatment of osteoporosis in patients suffering from Gaucher disease, specifying the challenges not yet addressed.

This study assessed the novel concept that osteoclast-derived Grem1 has regulatory functions in the skeletal response to calcium stress using an osteoclastic Grem1 conditional knockout (cKO) mouse model. The calcium stress was initiated by feeding cKO mutants and wildtype (WT) littermates a calcium-deficient diet for 2 weeks. Deletion of Grem1 in mature osteoclasts did not affect developmental bone growth nor basal bone turnover. In response to calcium depletion, male cKO mutants showed greater increases in osteoclastic resorption and trabecular bone loss than male WT littermates, indicating an enhanced skeletal sensitivity to calcium depletion in male mutants. The enhanced sensitivity to calcium depletion was sex-dependent, as female cKO mutants showed lower increases in osteoclastic resorption and bone loss than female WT littermates as well as male cKO mutants. The sex disparity in osteoclastic resorption response to calcium stress was intrinsic to osteoclasts since osteoclasts of male but not female cKO mutants showed greater in vitro bone resorption activity than osteoclasts of WT littermates of respective sex. Male cKO mutants displayed smaller bone formation response to calcium depletion than male WT littermates, while female mutants showed bigger bone formation response than female WT littermates, indicating that cKO mutants also displayed sex disparity in bone formation response. The sex disparity in bone formation response was not caused by intrinsic differences in osteoblasts but might be due to sex-dependent differential osteoclastic release of osteogenic factors. In summary, osteoclast-derived gremlin-1 has complicated and sex-dependent regulatory roles in skeletal response to calcium stress.

Military training improves tibial density, structure, and estimated strength; however, men and women may adapt differently. Most work performed in military populations has assessed changes in bone health during initial entry programs, a timeframe at the beginning of a service member's career when bones may be more adaptable to a novel mechanical stimulus. The purpose of this investigation was to examine changes in tibial volumetric bone mineral density (vBMD), structure, and estimated strength, and biomarkers of bone metabolism (P1NP, osteocalcin, TRAP5b, sclerostin) between male and female candidates measured at the start and end of United States Marine Corps Officer Candidates School (OCS), a 10-week military training program attended by older service members (~ 25 y/o) who may have previous military experience. Peripheral quantitative computed tomography (pQCT) of the tibia (n = 375) and blood draws (n = 385) were performed. Generalized linear mixed effects modeling compared changes between sexes over time. Increases in total and trabecular vBMD were observed at the 4% site in the total sample, but total and cortical vBMD decreased in female candidates at the 66% site. Periosteal circumference at the 38% and 66% sites increased in the total sample. Estimated strength increased similarly in male and female candidates at the 4% and 38% sites but only increased in male candidates at the 66% site. Concentrations of P1NP and osteocalcin increased similarly in both sexes, although sclerostin and TRAP5b decreased only in male candidates. Measures of tibial vBMD, width, and estimated strength increased following OCS consistent with adaptive bone formation.

Hypophosphatasia (HPP) is a congenital bone disease caused by tissue-nonspecific mutations in the alkaline phosphatase gene. It is classified into six types: severe perinatal, benign prenatal, infantile, pediatric, adult, and odonto. HPP with femoral hypoplasia on fetal ultrasonography, seizures, or early loss of primary teeth can be easily diagnosed. In contrast, pediatric, adult, and odonto types of HPP over 4 years of age are less likely to be diagnosed because they do not have typical symptoms. Consequently, it may be misdiagnosed as common osteoporosis, and treatments incompatible with HPP may be implemented. The purpose of this study was to analyze the effects of bisphosphonate preparations administration on the femur of Akp2^+/- mice, a mild-type HPP mice model. Zoledronic acid (Zol) was subcutaneously administered to 4-week-old Akp2^+/- mice at 1 mg/kg (volume: 200 μL) once a week for a total of 5 times. Afterward, spontaneous locomotor activity analysis was performed, and serum and femur bones were collected at 9 weeks of age. Additionally, micro-computed tomography (CT) analysis, histological analysis, and analysis of the expression levels of various marker proteins and genes were performed. Age-matched Akp2^+/+ mice served as controls. The results demonstrated that the administration of Zol to Akp2^+/- mice, compared to Akp2^+/+ mice, insufficiently promotive bone formation, torn femoral head cartilage, and decreased spontaneous locomotor activity. Therefore, it is important to accurately diagnose patients with mild-type HPP.

Swimming is a popular sport with several health benefits, but its effects on bone quality are controversial possibly due to distinct effects on different anatomical regions. Our aim was to investigate the effect of 8-month swimming on bone growth, mass, geometry, trabecular microarchitecture and osteocyte density of the lumbar vertebrae, femur and tibia of male rats. Wistar rat models were assigned to either a swimming (n = 10; 2h/d, 5 d/week) or a physically active control group (n = 10) for 8 months, after which they were sacrificed and their lumbar vertebrae, femur and tibia assessed for bone mass, cortical geometry, trabecular microarchitecture and osteocyte density through µ-CT and histology. Variables were compared between groups through independent samples t tests. Swimming animals displayed higher vertebral trabecular connectivity and lower trabecular separation compared to controls. However, femur length, trabecular and cortical bone mass and cortical thickness were lower compared to controls. At the tibia, animals from the swimming group also presented lower trabecular number and connectivity and higher trabecular separation. Osteocyte density at the femur and vertebra was similar between groups. Eight months of swimming negatively affected bone mass, cortical geometry and trabecular microarchitecture at the femur and tibia whilst having a favourable effect on vertebral trabecular microarchitecture. These results suggest that swimming has divergent effects on different anatomical regions.