Bone最新文献

Objective: Diffuse idiopathic skeletal hyperostosis (DISH) is increasingly recognised as a systemic condition associated with trabecular deterioration, and metabolic or vascular disruption. Within this spectrum, a phenotype characterised by accelerated skeletal progression has been described (Fast Ossifier, FO). We aimed to develop sex-specific prognostic indices derived from propensity score (PS) covariates-FOSSI-F (women) and FOSSI-M (men)-to stratify the risk of FO status within a population-based cohort.

Methods: Using longitudinal data from the Camargo Cohort, sex-stratified logistic models were constructed based on PS-derived upstream variables. Internal validation (bootstrap), discriminative performance (ROC/AUC) and exploratory analyses (non-linear models, clustering, Shapley-R² decomposition) were performed.

Results: We analysed 178 individuals (61 with FO; 64% women; mean age = 61 ± 7 years). FOSSI-F included visceral adiposity and hypertension, FOSSI-M included waist circumference, and both incorporated age, body mass index and cardiometabolic index. They showed high discriminatory capacity (AUC = 0.875 in women and 0.836 in men). Non-linear modelling revealed a broad sigmoid transition zone in women (approximately 5.8-9.6) and a sharp threshold-like pattern in men (0.45-0.71). In high FOSSI values, clustering analyses identified insulin resistance predominating in women and endocrine-inflammatory signals in men. Shapley analysis revealed TyG as the most influential factor in FOSSI-F variance (79.8%), while iPTH was in FOSSI-M (59.5%). Both indices correlated inversely with trabecular bone score (p < 0.0001).

Conclusion: FOSSI-F and FOSSI-M are sex-specific, PS-derived prognostic indices that capture latent metabolic-osteogenic susceptibility associated with FO status. Their strong internal discrimination supports their use for risk stratification and research-oriented interpretation.

Atypical femoral fractures (AFFs) are potential complications arising from long-term use of bone modifying agents such as denosumab. We describe a case of bilateral AFFs that was treated surgically in a middle-aged woman receiving oncologic doses of denosumab for treatment of metastatic breast cancer for seven years. In retrospect, early cortical change was present on scout computer tomography (CT) and positron emission tomography-computer tomography (PET-CT) prior to her left AFF. This case highlights the potential for earlier opportunistic AFF radiologic screening during cancer surveillance. It also describes our experience with preserving spinal bone density following the cessation of oncologic doses of denosumab through sequential zoledronic acid therapy.

Background: Radiofrequency echographic multi-spectrometry (REMS) is an emerging ultrasound-based technology for assessing bone mineral density (BMD). However, its correlation with the current gold standard, dual-energy X-ray absorptiometry (DXA), has not been comprehensively quantified. This study aimed to systematically review and meta-analyse the correlation between REMS and DXA.

Methods: We systematically searched databases for studies reporting correlations between REMS and DXA at the femoral neck and lumbar spine. Correlation coefficients were pooled via random-effects models after Fisher's z transformation. We performed subgroup analyses and meta-regression by study location, population, and sample size, along with sensitivity analyses.

Results: Seventeen studies comprising 8769 participants (90.9% female) for lumbar spine and 7464 participants (92.3% female) for femoral neck BMD were included. The pooled correlation coefficients between REMS and DXA were r = 0.819 (95% CI: 0.684-0.900) at the femoral neck and r = 0.769 (95% CI: 0.610-0.868) at the lumbar spine, indicating strong correlations. Correlations were comparable between studies from Italy and other countries but were lower in disease-specific populations and in smaller studies. Meta-regression confirmed significant effects of population type and sample size. Statistical heterogeneity was high (I² > 95%), and sensitivity analyses supported the robustness of the findings.

Conclusions: REMS-derived BMD demonstrates strong correlation with DXA at both anatomic sites. Correlation strength varies by population characteristics and study size. Further longitudinal studies are needed to assess REMS's ability to predict fractures and its performance in diverse clinical and community settings.

Aim: To evaluate the existing evidence on how maternal exposures during pregnancy and environmental factors during childhood influence bone health in offspring during the preschool years.

Methods: In this prospective cohort study, 146 Slovenian pregnant women and their offspring from birth to 7 years of age were monitored. The pregnant women's health status, anthropometry, serum 25-hydroxyvitamin D and adiponectin concentrations, dietary assessments, and quantitative ultrasound measurements of tibial bone speed of sound (SOS) value were recorded. The children's clinical status, anthropometric measurements, and tibial bone SOS value were assessed at birth, 1, 3 and 12 months, and 7 years of age, with diet assessed at 7 years.

Results: The longitudinal quantitative ultrasound measurements of bones revealed a significant effect of time on SOS measurements (F = 232.4, p < 0.001): SOS values were significantly lower at 1 and 3 months than at birth, while at 12 months and 7 years they were significantly higher than at birth, and 1 and 3 months. Infants with normal SOS showed a greater decline at 3 months. Low maternal 25(OH)D concentrations (r = -0.32; p = 0.01) and thyroid dysfunction (p < 0.05) were associated with lower SOS values at birth. Additionally, body mass index Z-score during the preschool period was associated with bone SOS values (at 1, 3 and 12 months and 7 years of age: p = 0.04; P = 0.01; p = 0.02, and p = 0.04, respectively).

Conclusion: Otherwise healthy preschool children with non-optimal bone mineral density were identified. Low maternal 25(OH)D, thyroid dysfunction, and the child's BMI Z-score were associated with lower SOS values. Due to the inclusion of participants with a healthier lifestyle, the data is not generalisable.

Background: Achondroplasia is associated with multisystem impairments that may require surgical interventions associated with high complication rates. The orthopaedic treatment landscape in achondroplasia varies globally, with some countries recommending surgical intervention more commonly. Achondroplasia-specific concerns related to preparation and conduct of surgical procedures necessitate careful consideration of treatment options in consultation with a multidisciplinary care team. The International Achondroplasia Forum convened a workshop in October 2024 to develop guiding principles for orthopaedic outcomes in achondroplasia, specifically spinal deformity, symptomatic spinal stenosis (and related neurological sequelae), upper and lower limb shortening/deformity (and associated functional limitations), chronic pain, and health-related quality of life, alongside achondroplasia-specific perioperative risk mitigation and post-surgical rehabilitation.

Results: Six guiding principles were agreed at the workshop with the aim of standardising and optimising orthopaedic care for people with achondroplasia. All principles were approved (votes in favour: 93%-100%) with a high level of agreement (range: 8.43-9.33). The International Achondroplasia Forum principles highlight the importance of a multidisciplinary team to guide treatment decisions and the need for essential procedures to be conducted at specialised institutions by clinicians experienced in the treatment of achondroplasia. Approaches to orthopaedic management include educating parents and caregivers; brace therapy, if necessary, to prevent or slow the development of thoraco-lumbar kyphosis; and weight management to minimise pain, dysfunction, and risk of complications. Pharmacological treatment is currently limited to vosoritide.

Conclusions: These guiding principles aim to improve outcomes for people with achondroplasia by reducing treatment heterogeneity and providing recommendations to caregivers. Consultation with an experienced and specialised multidisciplinary team, emphasis on non-surgical approaches to address orthopaedic symptoms and the conduct of essential surgical procedures only in specialised centres form the core of the guiding principles.

Osteoclasts and foreign body giant cells (FBGCs) are multinucleated cells derived from monocytes, but they have distinct functions. Osteoclasts resorb bone while FBGCs form in response to foreign material. Regarding bone implants, osteoclasts are responsible for implant integration, but also for bone resorption associated to implant loosening, while FBGCs play a role in the immune response to the foreign material. Little is known about which proteins in the local environment fine-tune the multinucleation of osteoclasts or FBGCs. One candidate is Activin A (ActA). It has been shown to induce larger, more active osteoclasts, but its effect on FBGC differentiation is unknown. We investigated the effect of ActA on the differentiation of osteoclasts and FBGCs from human CD14-positive monocytes. The number of multinucleated cells and the cell area was measured. qPCR was performed to assess the effect of ActA on gene expression. ActA's influence on osteoclast and FBGC formation was studied on plastic, bone and hydroxyapatite coated Titanium discs (ALD-HA). ActA induced fewer, but bigger and more active osteoclasts on plastic and bone. In contrast, ActA did not have an effect on FBGC number. On ALD-HA, ActA reduced the number of FBGCs, but did not influence osteoclast numbers. qPCR showed that ActA upregulated the expression of several genes such as TRAcP, CIITA, OLR1, RHOBTB1 and ALK4, but mainly in osteoclasts. These results show that ActA has a different effect on osteoclasts compared to FBGCs. This difference could be caused by a difference in the expression in the canonical ActA receptor ALK4.

Context: Experimental studies have suggested that the autocrine/paracrine effects of bone-derived Fibroblast Growth Factor 23 (FGF23) inhibit adipogenesis and promote osteoblastic differentiation of bone marrow stroma cells.

Objective: To examine whether there is relationship between circulating levels of FGF23 and bone marrow adiposity assessed by MRI.

Design: This cross-sectional study included 199 postmenopausal women without apparent disorders in phosphate homeostasis.

Setting: University Hospital of Lille, France.

Main outcome measure(s): C-terminal FGF23 (cFGF23, relative units (RU)/ml) and intact FGF23 (iFGF23, pg/ml). The Proton Density Fat Fraction (PDFF) of the lumbar spine and the proximal femur was assessed using MRI with chemical shift-based water-fat separation (WFI) and DXA of the hip and spine. Our main goal was to explore the relationships between PDFF, cFGF23, and iFGF23 levels in women who are postmenopausal. The relationships between cFG23, iFGF23, and body composition metrics were subsequently analyzed.

Results: A significant positive correlation was observed between cFGF23 and iFGF23 (R = 0.534, p < 0.0001). Significant inverse associations were found between cFGF23, iFGF23, and femoral neck PDFF (reciprocally, coefficient β (95%CI), -1.35 (-2.49 to -0.21), p = 0.020 and - 1.66 (-3.00 to -0.32), p = 0.016) after adjustment for age, recent fragility fracture, BMI, eGFR, and BMD. Conversely, there were no notable associations identified between cFGF23, iFGF23, and lumbar spine PDFF, regardless of whether adjustment models were applied. No significant associations were found between cFGF23, iFGF23, and body composition parameters (total body fat and visceral adipose tissue).

Conclusions: An inverse association was found between cFGF23, iFGF23, and proximal femur PDFF (particularly femoral neck PDFF), but not with lumbar spine PDFF. Moreover, cFGF23 and iFGF23 levels were not associated with other adipose deposits.

Objective: To identify inflammatory and hormonal biomarkers that predict bone loss at the contralateral (non-fractured) hip following hip fracture in males and females.

Methods: White participants who were not receiving pre-fracture glucocorticoids, sex-hormone therapy, or bone-active medications (100 males, 76 females) with hip fractures. Data were collected within 22 days of hip fracture and at 2, 6, and 12 months follow-up. Biomarkers were categorized into tertiles: estradiol (E), 25-hydroxyvitamin D3/D2 [25(OH)D], intact parathyroid hormone (iPTH), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), soluble tumor necrosis factor-α receptor 1 (sTNFα-R1), sex hormone-binding globulin (SHBG), and testosterone (T). Femoral neck bone mineral density (BMD) at the contralateral hip was assessed, and losses exceeding the mean decline were classified as greater than average. Logistic regression models, stratified by sex, were adjusted for confounders and evaluated selected biomarker associations.

Results: Among males, the 2nd (OR = 4.79, P = 0.012) and 3rd (OR = 6.36, P = 0.005) IGF-1 tertiles were associated with greater odds of BMD loss than the 1st tertile. The 3rd iPTH tertile (OR = 3.79, P = 0.037) was similarly associated with increased odds. Among females, the 3rd (OR = 0.20, P = 0.031) IL-1RA tertile was associated with lower odds of BMD loss compared to the 1st tertile, while the 2nd IL-6 tertile (OR = 5.99, P = 0.036) was associated with higher odds.

Conclusion: These findings suggest that inflammatory and hormonal biomarkers may be sex-specific predictors of accelerated BMD loss following hip fracture.

Lumbar vertebrae bone microstructure has been shown to correlate to compressive mechanical properties and display regional variability. However, properties quantified using bone samples may be dissimilar to those of the entire vertebra and sensitive to test methods. Additionally, significant differences in bone quantity across regions of lumbar vertebrae may assist in identifying fracture initiation sites. Further, most studies consider uniaxial compressive loading, whereas the in vivo spine experiences combined loading. The goal of the study was to quantify the relationship between human lumbar vertebrae microstructure and its fracture tolerance to combined compression and flexion. A second goal was to assess if significant regional variation of microstructure within the vertebral body could suggest a location for fracture initiation, given the relationship between microstructure and fracture tolerance. Human three-vertebra spine sections were exposed to dynamic compression-flexion loading, and then the center vertebral bodies were isolated and imaged via micro-computed tomography. Commercial evaluation software was used to quantify bone volume fraction (BV/TV) and cortical thickness (Ct.Th). Bayesian statistical analyses were performed to relate bone microstructure to fracture tolerance with age as a covariate and to quantify microstructural regional variation. BV/TV was significantly associated with fracture tolerance. For the typical donor at the average age, both BV/TV and Ct.Th were positively correlated to fracture tolerance. Ct.Th was region-dependent, while BV/TV was homogeneous. Further efforts may include identifying correlates for bone microstructure that can be measured from common clinical imaging modalities to aid in developing a practical predictive model.