Calcified Tissue International最新文献

MTX is an effective and widely used immunomodulatory drug for rheumatoid diseases. MTX osteopathy is a very rare and specific side effect, characterized by stress fractures at multiple locations in the lower extremity, hampering the patient's mobility by pain and loss of function. In clinical practice, osteoporosis and MTX osteopathy are repeatedly confused and a comparative workup is needed to clarity it's specifics. Furthermore, specific treatment options for MTX osteopathy need to be established. We compared patients suffering from MTX osteopathy to patients with osteoporosis (OPO). Patients underwent an extensive clinical workup including blood sampling, bone mineral density measurements, high-resolution peripheral quantitative computed tomography and muscular performance testing. Furthermore, treatment regimes in MTX osteopathy were compared with respect to regain of mobility and pain reduction. 83 patients with MTX osteopathy and 89 with OPO were included. Patients with MTX osteopathy did exhibit fractures predominantly at the lower extremity and pain scores were significantly higher (MTX: 6.75 ± 1.86 vs. OPO: 3.62 ± 2.95, p < 0.0001). MTX-caused mobility restriction was successfully reduced by treatment only if MTX was discontinued (pre-treatment: 2.16 ± 1.19 vs. post-treatment: 1.04 ± 0.87, p < 0.0001). Most mobility gain was achieved by involving anabolic treatment (anabolic: 2.1 ± 1.02 vs. antiresorptive: 1.09 ± 0.94, p < 0.05). In summary, MTX osteopathy is characterized by distinct lower extremity stress fractures leading to severe pain and immobility. Discontinuation of MTX is essential to enable treatment success and involving anabolic treatment seems to be more effectively in mobility regain as antiresorptive treatment alone.

This study aimed to evaluate the correlation between BMAT and bone quality, describe the long-term effects of ovariectomy on bone, and investigate BMAT's spatial distribution. Fifteen-months-old female Sprague‒Dawley rats were studied, comparing ovariectomized (OVX, n = 22) and sham-operated (SHAM, n = 11) groups at 6 months. Tibias were analyzed for bone microarchitecture, BMAT (microcomputed tomography), mineral parameters (quantitative backscattered electron imaging), and bone composition (Raman microspectroscopy). The OVX tibias showed severe trabecular bone loss (lower bone volume/total volume, p < 0.001) with increased BMAT (higher adipose volume per marrow volume, p < 0.001), decreased mineral content (lower calcium concentration, p < 0.001), and altered organic components (lower mineral/matrix ratio in new bone, p = 0.03 trabecular surface, p < 0.001 trabecular core). When the data are pooled over both groups (SHAM and OVX), the adipose volume/marrow volume ratio was negatively correlated with bone volume/total volume (r =  - 0.79, p < 0.001) and mineral/matrix ratio (r =  - 0.37, p = 0.04 trabecular surface; r =  - 0.65, p < 0.001 trabecular core) and positively correlated with crystallinity (r = 0.55, p = 0.001 trabecular surface; r = 0.49, p = 0.006 trabecular core). The mineral/matrix ratio of trabecular surface new bone was strongly negatively correlated with the adipose compartment nearest to the bone surface. These findings suggest mechanisms underlying BMAT's role in bone resorption.

In conversations about bone loss and the importance of calcium homeostasis, patients frequently inquire about the association with arterial calcifications. Although a relationship between bone loss and the occurrence of vascular calcifications is suspected, it is not yet fully investigated and understood. This study aims to analyze associations between bone mineralization, structure, and vascular calcification at the lower leg in patients with low bone mineral density in HR-pQCT. We retrospectively analyzed 774 high-resolution quantitative computed tomography (HR-pQCT) scans of the distal tibia for the presence of vascular calcifications. After sex-specific propensity score matching for age and BMI to account for confounders, 132 patients remained for quantification of bone microstructure, bone density, lower leg arterial calcification (LLAC), and laboratory parameters of bone turnover. The interactions between bone parameters and vascular calcification were quantified by regression analyses. The calcium metabolism was not different between individuals with and without LLAC, nor oral calcium supplementation. Female patients with LLAC had a higher cortical perimeter (p = 0.016) compared to female patients without LLAC, whereas male patients with LLAC had lower cortical pore diameter than male patients without LLAC (p = 0.027). The appearance of LLAC was sex specifically associated with bone parameters. In female patients, only plaque density was associated with HR-pQCT bone parameters and age, whereas in male patients, plaque volume was associated with HR-pQCT parameters of the distal tibia. Female patients exhibit an increasing plaque density depended on age and trabecular thinning. Decreasing cortical pore diameter and trabecular number along with increasing bone mineralization are linked to increasing plaque volume in male patients.

The effects of androgens on women's bone health are not fully understood. Mendelian randomization (MR) studies using sex-combined data suggest that sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT) causally affect bone traits. Given significant sex differences in hormone regulation and effects, female-specific MR studies are necessary. In the current study, we explored the causal relationships of SHBG, BioT, and total testosterone (TT) with forearm fracture (FAFx) risk in women using two-sample MR analyses. We utilized a unique female-specific FAFx outcome dataset from three European biobanks (UFO, HUNT, Estonian Biobank) comprising 111,351 women and 8823 FAFx cases, along with female-specific genetic instruments of SHBG, BioT, and TT identified in the UK Biobank. We also assessed bone mineral density (BMD) at the forearm (FA), femoral neck (FN), and lumbar spine (LS) using female-specific GWAS data from the GEFOS consortium. High SHBG (odds ratio per standard deviation increase (OR/SD): 1.53, 95% confidence intervals (CIs): 1.34-1.75), low BioT (OR/SD: 0.77, 0.71-0.84) and low TT (OR/SD 0.90, 0.83-0.98) were causally associated with increased FAFx risk. BioT was positively, and SHBG inversely, causally associated with especially FA-BMD, but also LS-BMD and FN-BMD, while TT was only significantly positively associated with FA-BMD and LS-BMD. We propose that endogenous androgens and SHBG are important for women's bone health at distal trabecular-rich bone sites such as the distal forearm and may serve as predictors for FAFx risk.

Purpose: Patients with osteoporosis are at risk of fractures, which can lead to immobility and reduced quality of life. Early diagnosis and treatment are crucial for preventing fractures, but many patients are not diagnosed until after a fracture has occurred. This study aimed to evaluate the performance of 10 osteoporosis screening tools (OSTs) in rural communities of Taiwan. In this prospective study, a total of 567 senior citizens from rural communities underwent bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA) and ten OSTs were administered. Discrimination analysis was performed using the area under the receiver operating characteristic curve (AUROC). Primary outcomes included area under curve (AUC) value, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The DXA examination revealed that 63.0% of females and 22.4% of males had osteoporosis. Among females, Osteoporosis Index of Risk (OSIRIS) and Osteoporosis Self-Assessment Tool for Asians (OSTA) presented the best AUC value with 0.71 (0.66-0.76) and 0.70 (0.66-0.75), respectively. Among males, BWC had the best AUC value of 0.77 (0.67-0.86), followed by OSTA, Simple Calculated Osteoporosis Risk Estimation (SCORE), and OSIRIS. OSTA and OSIRIS showed acceptable performance in both genders. The specificity of Fracture Risk Assessment Tool (FRAX-H), SCORE, National Osteoporosis Foundation Score, OSIRIS, Osteoporosis Risk Assessment Instrument, Age, Bulk, One or Never Estrogen (ABONE), and Body weight criteria increased in both genders after applying the optimum cut-off. Considering it high AUC and simplicity of use, OSTA appeared to be the recommended tool for seniors of both genders among the ten OSTs. This study provides a viable reference for future development of OSTs in Taiwan. Further adjustment according to epidemiological data and risk factors is recommended while applying OSTs to different cohorts.

Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling leading to various complications, such as bone deformity, deafness, secondary osteoarthritis, and pathological fracture. Pain is the most common presenting symptom of PDB, but it is unclear to what extent this is due to increased metabolic activity of the disease, complications, or unrelated causes. We conducted a cross-sectional study of 168 people with PDB attending secondary care referral centres in the UK. We documented the presence of musculoskeletal pain and sought to determine its underlying causes. Musculoskeletal pain was reported by 122/168 (72.6%) individuals. The most common cause was osteoarthritis of joints distant from an affected PDB site in 54 (44.3%), followed by metabolically active PDB in 18 (14.7%); bone deformity in 14 (11.4%); osteoarthritis of a joint neighbouring an affected site in 11 (9.0%), neuropathic pain in 10 (8.2%), and various other causes in the remainder. Pain was more common in women (p<0.019) and in older individuals (p<0.001). Circulating concentrations of macrophage colony-stimulating factor (M-CSF) were significantly higher in those with pain (p = 0.008), but there was no difference between groups of patients with and without pain in concentrations of interleukin-6 (IL-6) or biochemical markers of bone turnover. Pain is a common symptom in PDB but is most often due to osteoarthritis at an unaffected site. The study illustrates the importance of fully evaluating people with PDB to determine the underlying cause of pain so that management can be tailored appropriately.

To investigate the potential mechanism of Morinda officinalis F. C. How polysaccharides (MOPs) in regulating osteoclast differentiation and apoptosis through miR-214-3p and its target protein. Ovariectomy was performed in 8-week female C57BL6 mice to establish the postmenopausal osteoporosis (PMOP) model. Mice were treated immediately with 500 mg/kg of MOPs (prevention group); others were treated 2 weeks after operation (treatment group). Left femur bone mineral density (BMD) was examined. RAW264.7 cells were administered with receptor activator of NF-κB ligand (RANKL) to establish the osteoclast (OC) model and treated with serum containing 1 or 2 g/kg of MOPs. Apoptosis-related indexes, miR-214-3p, and Expressed Developmentally Down-regulated 4-Like (NEDD4L) were detected by western blot, quantitative real-time-reverse transcription polymerase chain reaction (qRT-PCR), and flow cytometry. OC received a miR-214-3p inhibitor or NEDD4L small interfering RNA (siRNA). MOPs reversed the PMOP-induced changes in bones. Compared with the RANKL group, MOPs increased the apoptosis and related markers in OCs. MOPs decreased the femur miR-214-3p of PMOP mice (P < 0.001). Higher concentrations of MOPs reversed the upregulation of miR-214 mRNA in OCs (P < 0.001). miR-214-3p inhibitor increased the expression of Bax and CC3 (P < 0.01) and decreased the expression of Bcl-2 (P < 0.05). NEDD4L is targeted by miR-214. NEDD4L was upregulated in the RANKL + MOPs group (P < 0.01). miR-214-3p inhibitor increased the upregulation of NEDD4L induced by MOPs (P < 0.05). siRNA NEDD4L significantly reversed the inhibition of MOPs on osteoclast differentiation with miR-214-3p inhibitor (P < 0.01). MOPs effectively prevent PMOP by inhibiting osteoclastogenesis and inducing OC apoptosis through the miR-214-3p/NEDD4L pathway.

Osteoporosis is a skeletal disorder characterized by abnormal bone microarchitecture and low bone mineral density (BMD), responsible for an increased risk of fractures and skeletal fragility. It is a common pathology of the aging population. However, when osteoporosis occurs in children or young adults, it strongly suggests an underlying genetic etiology. Over the past two decades, several genes have been identified as responsible for this particular kind of considered monogenic early-onset osteoporosis (EOOP) or juvenile osteoporosis, the main ones being COL1A1, COL1A2, LRP5, LRP6, WNT1, and more recently PLS3. In this study, the objective was to characterize a large cohort of patients diagnosed with primary osteoporosis and to establish its diagnosis yield. The study included 577 patients diagnosed with primary osteoporosis and its diagnosis yield was established. To this end, next-generation sequencing (NGS) of a panel of 21 genes known to play a role in bone fragility was carried out. A genetic etiology was explained in about 18% of cases, while the others remain unexplained. The most frequently identified gene associated with EOOP is LRP5, which was responsible for 8.2% of the positive results (47 patients). As unexpected, 17 patients (2.9%) had a variant in PLS3 which encodes plastin 3. Alterations of PLS3 are associated with dominant X-linked osteoporosis, an extremely rare disease. Given the rarity of this disease, we focused on it. It was observed that males were more affected than females, but it is noteworthy that three females with a particularly severe phenotype were identified. Of these three, two had a variant in an additional gene involved in EOP, illustrating the probable existence of digenism. We significantly increase the number of variants potentially associated with EOOP, especially in PLS3. The results of our study demonstrate that molecular analysis in EOOP is beneficial and useful.

Lipid accumulation product (LAP) has a positive effect on spinal bone mineral density (BMD). However, once LAP levels exceed 27.26, the rate of spinal BMD increase slow down or even decline. This indicates a biphasic relationship between lipid metabolism and BMD, suggesting potential benefits within a certain range and possible adverse effects beyond that range. This study aimed to investigate the potential association between LAP index and BMD in US adults, as well as to explore the presence of a potential saturation effect in this relationship. This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018. A multiple stepwise regression model was employed to examine the association between LAP index and total spinal BMD. Additionally, a generalized additive model and a smooth curve fitting algorithm were utilized to examine the relationship, and saturation effect study was conducted to determine the saturation level. The calculation formula of LAP used in the study was: (LAP = (waist circumstances (WC) (cm) - 58) × triglyceride (TG) (mmol/L)) for women, and (LAP = (WC (cm) - 65) × TG (mmol/L)) for men. The study involved a total of 7913 participants aged 20 years or older. Through multiple stepwise regression analysis, it was found that individuals with higher LAP scores exhibited higher total spinal BMD. In both the crude and partially adjusted models, total spinal BMD was significantly higher in the highest LAP quartile (Q4) compared to the lowest LAP quartile (Q1) (P < 0.05). Utilizing a generalized additive model and smooth curve, a nonlinear relationship between LAP and total spinal BMD was observed. Furthermore, the study identified the saturation value of LAP to be 27.26, indicating a saturation effect. This research highlights a nonlinear relationship between LAP and total spinal BMD, along with the presence of a saturation effect.

Rare diseases (RDs) bear a significant challenge to individuals, healthcare systems, and societies. The European reference network on Rare BONe diseases (ERN BOND) is committed to improving multidisciplinary, patient-centred care for individuals with rare bone and mineral diseases (RBMDs). Its affiliated project, the European registries for rare bone and mineral conditions (EuRR-Bone) collects data using two different platforms, an electronic surveillance system (e-REC) that captures the occurrence of RBMDs and the Core Registry, a platform with the infrastructure for collecting Core data fields and longitudinal generic and condition-specific information. With emerging registries and the overlap with other ERNs, it is key to maintain the capability of the platforms to adapt to the needs of the network and the community whilst adhering to quality and FAIR (findable, accessible, interoperable, and reusable) principles. This binomial ensures long-term sustainability and potential advances in the care pathway of RBMDs whilst promoting good practice standards within Europe and beyond.