Bone [JOURNAL]
Sun
200 papers
Correlation between radiofrequency echographic multi-spectrometry (REMS) and dual-energy X-ray absorptiometry (DXA): A systematic review and meta-analysis.
Liu RY, Liu E
Bone · 2026 May · PMID 41651205 · Publisher ↗
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...
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 (I > 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.
Practical guidance for clinicians to optimise orthopaedic outcomes in achondroplasia: International Achondroplasia Forum guiding principles.
Kunkel P, Vleggeert-Lankamp C, Riganti S … +9 more , Leiva-Gea A, Boero S, Fredwall S, Mohnike K, Mortier G, Okada K, Sessa M, Irving M, International Achondroplasia Forum
Bone · 2026 May · PMID 41651204 · Publisher ↗
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...
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.
Longitudinal changes in bone quantitative ultrasound measurements in healthy pre-school children: Maternal and child determinants.
Cerar S, Benedik E, Pikel TR … +4 more , Rogelj I, Pražnikar ZJ, Petelin A, Soltirovska-Šalamon A
Bone · 2026 May · PMID 41651203 · Publisher ↗
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 coh...
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.
Metabolic and osteogenic susceptibility in DISH: A prognostic index from propensity score modelling.
Pariente E, Martín-Millán M, Maamar M … +7 more , Pardo-Lledías J, Basterrechea H, Petitta B, Bianconi C, Ramos-Barrón C, Martínez-Taboada V, Hernández JL
Bone · 2026 May · PMID 41651202 · Publisher ↗
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 phenot...
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-R 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.
Activin-A has dual roles in osteoclast formation and foreign body giant cell differentiation from human CD14 monocytes.
Kylmäoja E, Kauppinen S, Abushahba F … +6 more , Finnilä M, Ritala M, Lehenkari P, Tuukkanen J, de Vries TJ, Schoenmaker T
Bone · 2026 May · PMID 41643827 · Publisher ↗
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...
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.
Dual inhibition of sclerostin and Notum induces synergistic osteoanabolic action in mice.
Choi RB, Hoggatt AM, Horan DJ … +4 more , Cunningham CJ, Brommage R, Powell DR, Robling AG
Bone · 2026 May · PMID 41638381 · Full text
Expanding the number of clinically approved choices for osteoanabolic therapy represents the next hurdle on the osteoporosis treatment horizon. The WNT pathway is involved in stimulating new bone formation, and the most...
Expanding the number of clinically approved choices for osteoanabolic therapy represents the next hurdle on the osteoporosis treatment horizon. The WNT pathway is involved in stimulating new bone formation, and the most recent FDA-approved anabolic therapy-sclerostin neutralizing antibody-works by stimulating the WNT pathway in bone. The challenge with all current osteoanabolic therapies is the short treatment window in which they are efficacious. One strategy to dealing with this limited anabolic window is to further maximize bone formation during the window, using combination therapy. For example, simultaneous pharmacological or genetic inhibition of the WNT antagonists sclerostin and DKK1 potentiate the already strong effects of sclerostin inhibition alone, particularly in cancellous bone. Considerable interest has emerged regarding other candidates that might be co-inhibited along with sclerostin to potentiate its effects in bone, with specific action on cortical bone. In this communication, partnering sclerostin inhibition with the inhibition of another secreted WNT antagonist, NOTUM, is explored. NOTUM is a secreted WNT deacylase that inactivates WNT ligands and has preferential effects on cortical bone. To evaluate combination therapy involving sclerostin/NOTUM inhibition, double knockout mice for Sost and Notum (Sost;Notum) were generated and compared to single knockouts and WT controls. Further experiments were conducted using pharmacologic inhibitors, rather than genomic mutations, for sclerostin (sclerostin neutralizing antibody) and a small molecule inhibitor of NOTUM (LP-922056). Each experiment included evaluation by DXA-derived radiography, μCT, biomechanical testing and bone dynamic histomorphometry. Deletion of Notum alone had mild cortical effects but co-deletion of Sost and Notum improved cortical and some cancellous parameters significantly beyond Sost mice. Co-inhibition of the protein products with antibody/small molecule were less synergistic, with only a small cortical effect, particularly in younger mice. Taken together, the results suggest the potential to improve efficacy of sclerostin inhibition using NOTUM inhibition is promising, but development of additional NOTUM inhibiting tools and optimization of current tools might be necessary to strengthen the partnership.
Quantitative assessment of the alignment between human trabecular microstructural orientation and mechanical anisotropy: Implications for Wolff's Law.
Xiao P
Bone · 2026 May · PMID 41638380 · Publisher ↗
Trabecular bone exhibits a highly organized microarchitecture that adapts to its mechanical loading environment, a concept fundamentally described by Wolff's law. However, direct quantitative evidence linking the trabecu...
Trabecular bone exhibits a highly organized microarchitecture that adapts to its mechanical loading environment, a concept fundamentally described by Wolff's law. However, direct quantitative evidence linking the trabecular microstructural orientation with mechanical anisotropy remains limited. In this study, we quantitatively assessed the alignment between trabecular microstructural orientation and the apparent stiffness tensor using a micro-CT-based finite element (μFE) framework. Fabric tensors and the orientations of individual trabecular plates and rods were derived using the Mean Intercept Length (MIL) method and Individual Trabecula segmentation (ITS) analysis, respectively. The apparent stiffness tensors were obtained through μFE models subjected to three uniaxial compression and three pure shear loading cases. The results demonstrated a strong alignment between the fabric tensor and the apparent stiffness tensor, with an overall alignment index (λ¯) of 0.92 (IQR: 0.09). Trabecular plates exhibited a high degree of alignment with the apparent stiffness tensor (λ¯: 0.88, IQR: 0.15), whereas trabecular rods demonstrated a substantially lower degree of alignment (λ¯: 0.36, IQR: 0.19). Moreover, the alignment between the principal axis of trabecular plates and the apparent stiffness tensor increased with the degree of anisotropy (DA), while the alignment of trabecular rods decreased with increasing DA. These findings provide quantitative evidence supporting Wolff's law, confirming that trabecular bone architecture is structurally optimized to align with habitual mechanical stress pathways, and highlight the dominant role of trabecular plates in governing the mechanical competence of cancellous bone.
Site-specific inverse associations between FGF23 levels and marrow adiposity content at the proximal femur in post-menopausal women.
Paccou J, Badr S, Ramdane N … +3 more , Michou L, Courbon G, Mentaverri R
Bone · 2026 Apr · PMID 41619894 · Publisher ↗
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 ce...
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.
Sex-specific biomarkers predict bone mineral density loss at the contralateral hip after hip fracture.
Rathbun AM, Shardell MD, Ryan AS … +5 more , Stains JP, Orwig DL, Magaziner JS, Slobogean GP, Hochberg MC
Bone · 2026 May · PMID 41619893 · Publisher ↗
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...
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, 25-hydroxyvitamin D3/D2, 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, sex hormone-binding globulin, and testosterone. 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.
Cellular alterations in trabecular bone following monocrotaline-induced right heart failure in rats.
Kaneguchi A, Takagi R, Sunagawa S … +5 more , Azuma Y, Ishinaka K, Umehara T, Yamaoka K, Ozawa J
Bone · 2026 Apr · PMID 41616896 · Publisher ↗
Heart failure is associated with bone deterioration, consequently increasing the risk of fractures. Fractures occurring in patients with heart failure are associated with increased hospitalization and mortality rates, ma...
Heart failure is associated with bone deterioration, consequently increasing the risk of fractures. Fractures occurring in patients with heart failure are associated with increased hospitalization and mortality rates, making the prevention of bone deterioration a critical clinical concern. The cellular alterations associated with heart failure-related bone deterioration remain largely unexplored. This study aimed to investigate histological changes in trabecular bone following heart failure, with a focus on characterizing cellular alterations associated with bone deterioration. Male Wistar rats were assigned to either a control or heart failure group. The heart failure group was administered monocrotaline intraperitoneally, while the control group received a vehicle injection. Twenty-eight days post-injection, histological analyses were conducted on the proximal humerus, proximal femur, distal femur, and proximal tibia. Compared to controls, rats in the heart failure group exhibited a significant reduction in trabecular bone volume at all examined sites. In parallel, they showed a significant increase in the number of osteoclasts, an increased empty lacuna ratio (indicative of osteocyte loss), and a greater proportion of caspase-3-positive osteocytes (a marker of apoptosis). These changes were consistently observed across all anatomical locations. These findings suggest that heart failure induces osteocyte apoptosis, which may drive osteoclastogenesis and lead to trabecular bone loss. The fact that similar changes were observed consistently across all anatomical sites suggests that systemic factors associated with heart failure, rather than localized influences, are likely the primary contributors to bone deterioration. Understanding these processes could inform novel therapeutic strategies to prevent bone loss following heart failure.
Multiexon COL1A2 deletion as a rare mechanism in osteogenesis imperfecta: Case report and literature review.
Oliveira D, Almeida PM, Franco S … +6 more , Pina R, Cerqueira R, Modamio-Hoybjor S, Heath KE, Sousa SB, Ramos F
Bone · 2026 May · PMID 41616895 · Publisher ↗
BACKGROUND: Osteogenesis imperfecta (OI) is mostly caused by pathogenic variants in COL1A1/COL1A2; while single nucleotide variants predominate, multiexon copy number variants (CNVs) remain under-recognised contributors...
BACKGROUND: Osteogenesis imperfecta (OI) is mostly caused by pathogenic variants in COL1A1/COL1A2; while single nucleotide variants predominate, multiexon copy number variants (CNVs) remain under-recognised contributors with incompletely defined phenotypic impacts. METHODS: We investigated a fetus presenting severe skeletal dysplasia using NGS with CNV calling and MLPA, clinical and radiologic assessments, and transcript analysis of maternal fibroblasts. We also reviewed the literature and curated databases for reported multiexon COL1A2 deletions. RESULTS: The fetus exhibited lethal OI type II features, including progressive long bone shortening and bowing, multiple fractures, diffuse hypomineralisation, and a bell-shaped thorax. Genetic analysis revealed a heterozygous in-frame COL1A2 exons 4-17 deletion. Maternal testing identified low-level mosaicism for this large deletion alongside a germline in-frame deletion of exons 12-17. Detailed breakpoint analysis of the exon 12-17 deletion revealed a complex rearrangement characterised by the insertion of an inverted duplicated segment of exon 3 and intron 3 at the deletion junction. Despite these findings, the mother showed only joint hypermobility and a family history of osteoporosis, without overt features of OI. CONCLUSIONS: N-terminal in-frame COL1A2 deletions show variable expressivity, including perinatal lethality. We report a novel, complex and likely unstable genomic rearrangement which probably predisposed to a secondary, larger deletion. Integrated CNV analysis and parental studies are crucial to ensure accurate recurrence risk counselling.
Bone mineral density in rheumatoid arthritis patients on antirheumatic therapies: a systematic review.
Taylor-Williams O, Godwin R, Carvallio R … +3 more , Taylor-Williams M, Barrett C, Inderjeeth C
Bone · 2026 May · PMID 41616894 · Publisher ↗
Rheumatoid Arthritis (RA) is associated with increased fracture risk due to systemic bone loss. Whilst new disease modifying antirheumatic drugs (DMARD) have improved disease control, their impacts on bone mineral densit...
Rheumatoid Arthritis (RA) is associated with increased fracture risk due to systemic bone loss. Whilst new disease modifying antirheumatic drugs (DMARD) have improved disease control, their impacts on bone mineral density (BMD) remains controversial. This systematic review investigates the effects of conventional synthetic (cs), biologic (b), and targeted synthetic (ts) DMARDs on BMD in RA patients. 13,340 records were screened, with 46 studies meeting the inclusion and exclusion criteria, published on PROSPERO (CRD42024534452). Included studies were analysed by their use of specific DMARD, glucocorticosteroids (GCS), antiosteoporotic therapy (AOT) and disease activity. csDMARD appear beneficial to BMD, and on the balance of evidence bDMARD and tsDMARD appear to have a greater effect on BMD. Encouragingly, early data suggests some csDMARD, bDMARD, tsDMARD may be superior to others, however, further research is required to confirm this. Future researchers should consider DMARD mechanism of action on BMD and examine the role of specific csDMARD, bDMARD, and tsDMARD in large cohort studies and trials.
COVID-19 increases the risk for hip fractures in older subjects - A register-based Swedish population study.
Kajba K, Xu Y, Santosa A … +4 more , Bygdell M, Ohlsson C, Nyberg F, Li H
Bone · 2026 Apr · PMID 41616893 · Publisher ↗
Hip fractures are a significant public health concern, associated with high morbidity and mortality. This population-based cohort study investigated whether COVID-19 increased hip fracture risk in Swedish adults. The stu...
Hip fractures are a significant public health concern, associated with high morbidity and mortality. This population-based cohort study investigated whether COVID-19 increased hip fracture risk in Swedish adults. The study included 3,931,893 Swedish residents aged ≥50 years as of January 1st 2020, and recorded 50,883 incident hip fractures during follow-up, until the end of 2022. The exposure of interest was COVID-19 confirmed via national registries during the study period, with 711,879 (18.1%) identified cases. The primary outcome was hip fracture incidence. Secondary outcomes included fractures of the proximal humerus and wrist. Association between COVID-19 and fractures was estimated using Cox proportional hazards regression with time-varying exposure, adjusting for demographic and socioeconomic characteristics, frailty index, previous comorbidities, prior medication use, and COVID-19 vaccination status. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). In fully adjusted models, COVID-19 was associated with a 43% higher risk of hip fractures (HR 1.43, 95% CI 1.36-1.50), with stronger association observed in men (HR 1.57, 95% CI 1.45-1.71) than in women (HR 1.36, 95% CI 1.28-1.45). Age-stratified analyses revealed significant associations in individuals aged ≥65 years (men: HR 1.68, 95% CI 1.54-1.82; women: HR 1.42, 95% CI 1.33-1.51), but not in those aged 50-65 years. Associations with proximal humerus and wrist fractures were less pronounced. These findings suggest that COVID-19 is associated with a substantially increased risk of hip fracture, especially among individuals aged ≥65 years old, underscoring the importance of targeted fracture prevention in this group after COVID-19.
Sclerostin-targeted delivery of PCSK9 siRNA reverses osteoporosis in OVX mice.
Wu H, Huang L, Song F … +7 more , Zhou Y, Wu Y, Zheng J, Yin Z, Wei Y, Sun H, Huang C
Bone · 2026 Apr · PMID 41611110 · Publisher ↗
The role of PCSK9 in bone metabolism has recently emerged as a critical area of research. This study identifies a significant upregulation of PCSK9, approximately 1.2-fold in ovariectomized (OVX) mice serum, approximatel...
The role of PCSK9 in bone metabolism has recently emerged as a critical area of research. This study identifies a significant upregulation of PCSK9, approximately 1.2-fold in ovariectomized (OVX) mice serum, approximately 3-fold in OVX mice bone marrow stem cells, which correlates strongly with decreased bone mineral density, implicating PCSK9 in estrogen deficiency-induced bone loss. Genetic knockout of PCSK9 was found to ameliorate osteoporosis by improving bone microarchitecture, increasing trabecular bone volume fraction (BV/TV) by 50%, enhancing bone formation (serum PINP increased by 30%), and bone resorption (serum β-CTX increased by 10%), confirming its dual regulatory function. Based on these findings, we engineered a bone-targeted exosome delivery system by surface functionalizing exosomes with an anti-sclerostin (anti-SCL) fragment. This novel system facilitated efficient bone-specific enrichment (fluorescence intensity in bone increased by 60%) and the successful delivery of siPCSK9, resulting in potent silencing of bone marrow PCSK9 expression. In OVX osteoporotic mice, this targeted intervention markedly attenuated bone loss. A 2-fold increase in bone mass was observed relative to the untreated OVX group. Our work not only elucidates a pivotal role of PCSK9 in osteoporosis pathogenesis but also provides a compelling proof-of-concept for exosome-based precision therapy, offering substantial potential for clinical translation.
Does lumbar vertebra bone microstructure relate to combined loading fracture tolerance and inform fracture initiation site?
Tushak SK, Chernyavskiy P, Gates B … +2 more , George C, Kerrigan JR
Bone · 2026 Apr · PMID 41605292 · Publisher ↗
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...
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.
Calcium, FSH, and the changing bones of menopause: A longitudinal look at the silent transformation.
Puranda JL, Weber VMR, Doucet É … +1 more , Adamo KB
Bone · 2026 Apr · PMID 41605291 · Publisher ↗
INTRODUCTION: Osteoporosis poses a health risk to post-menopausal females. The menopause transition is associated with hormone fluctuations (e.g., follicle-stimulating hormone (FSH), estrogen), and other biochemical and...
INTRODUCTION: Osteoporosis poses a health risk to post-menopausal females. The menopause transition is associated with hormone fluctuations (e.g., follicle-stimulating hormone (FSH), estrogen), and other biochemical and physiological changes that contribute a decline in bone mineral density (BMD). This will investigate the relationship between biochemical and physiological markers of BMD across the menopause transition. METHODS: Fifty-six middle-aged females who completed their menopause transition were included in this longitudinal sub-analysis. Participants were recruited from the Ottawa/Gatineau region. Menopause status was classified using menstrual history and FSH plasma levels. BMD and body composition were assessed using dual-energy x-ray absorptiometry (DXA). Additional measures included BMI, cardiorespiratory fitness (VO), diet calcium and Vitamin D, and biochemical markers (i.e., FSH, cortisol, calcium). Statistical analysis included repeated measures analysis of variance, linear mixed modeling, and group-based trajectory modeling to identify distinct FSH trajectory groups and their associations with BMD changes over time. RESULTS: Serum calcium was negatively associated with BMD at the lumbar spine [β: -0.0799, 95% confidence interval (CI): -0.139; -0.020, p = 0.009]. Further, the high FSH trajectory group experienced a greater decrease in BMD across the 5-year period, at the femur neck [β: 0.067, CI: 0.050; 0.084 vs. β: 0.035, CI: 0.021; 0.048; p = 0.003] and total body [β: 0.045, CI: 0.035; 0.055 vs. β: 0.028, CI: 0.020; 0.036; p = 0.007] than the low FSH trajectory group. CONCLUSION: Associations between serum calcium and lumbar spine BMD, and a greater BMD decline in individuals with high FSH levels were revealed. This information suggests that serum calcium and FSH should be monitored throughout the menopause transition to protect BMD.
Impact of abdominal adiposity correction on trabecular bone score (TBS) in obese women: A comparative study of software versions 3.0 and 4.0 with a predictive model.
Starck FPM, Silva BC, Borba VZC
Bone · 2026 Apr · PMID 41579916 · Publisher ↗
PURPOSE: To evaluate the impact of soft-tissue thickness correction on trabecular bone score (TBS) in obese women across different BMI categories, comparing software versions 3.0 and 4.0, and to examine their association...
PURPOSE: To evaluate the impact of soft-tissue thickness correction on trabecular bone score (TBS) in obese women across different BMI categories, comparing software versions 3.0 and 4.0, and to examine their associations with bone mineral density (BMD), fracture occurrence, and clinical variables. METHODS: This cross-sectional study included 247 obese women (BMI ≥30 kg/m) who underwent lumbar spine densitometry with TBS assessment using versions 3.0 and 4.0 of the TBS iNsight® software. Demographic, anthropometric, and BMD data were analyzed. Correlations and multivariate linear regression models were used to assess associations between TBS 4.0, BMD, fractures, and clinical parameters. RESULTS: TBS 4.0 were lower than TBS 3.0 across all BMI categories (p < 0.001), with the largest reductions observed in women with BMI ≥ 37 kg/m. Classification of TBS changed in 34% of cases when using version 4.0, with a greater proportion reclassified to degraded categories. TBS 4.0 showed a positive correlation with lumbar spine BMD (r = 0.51, p < 0.001) and BMI (r = 0.17, p = 0.007), but showed no significant correlation with abdominal wall thickness (r = -0.08, p = 0.229). The correlation between TBS and BMI was stronger for version 3.0 than for version 4.0 (r = 0.32 vs. r = 0.17, respectively). In multivariate analysis, abdominal wall thickness emerged as an independent predictor of TBS 4.0. A multivariate regression model including TBS 3.0, age, L1-L4 BMD, and abdominal wall thickness explained 86% of the variability in TBS 4.0, enabling estimation of TBS 4.0 from clinical variables and the earlier software version. Women with fractures showed lower TBS values, though not significant. CONCLUSIONS: The TBS 4.0, by incorporating automatic correction for soft-tissue thickness, provides lower values that possibly better characterize trabecular microarchitecture in individuals with obesity, especially in those with higher BMIs, and mitigates the bias attributable to differences in body composition observed with previous versions of the TBS software.
Corrigendum to "Pulsed electromagnetic fields inhibit human osteoclast formation and gene expression via osteoblasts" [Bone 106 (2018) 194-203 (ISSN: 8756-3282)].
He Z, Selvamurugan N, Warshaw J … +1 more , Partridge NC
Bone · 2026 Apr · PMID 41571532 · Publisher ↗
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Nutraceuticals in orthopedic implant osseointegration: Mechanisms, evidence, and clinical perspectives.
Ricciardi G, Donadio D, Ficarra G … +9 more , Nasso C, Foglia P, Bitto A, Scarfì R, Fadda G, Corpina F, Cutè E, Martini M, Ferlazzo M
Bone · 2026 Apr · PMID 41570965 · Publisher ↗
Total joint replacement is one of the most successful interventions in modern orthopedics, but long-term outcomes depend on effective osseointegration. Pharmacological strategies such as bisphosphonates, estrogens, and m...
Total joint replacement is one of the most successful interventions in modern orthopedics, but long-term outcomes depend on effective osseointegration. Pharmacological strategies such as bisphosphonates, estrogens, and monoclonal antibodies can enhance bone-implant integration, but their clinical use is limited by adverse effects. Nutraceuticals, including polyphenols, carotenoids, and polyunsaturated fatty acids, have emerged as promising adjuncts to support bone health and osseointegration, thanks to their safety profile and biological activity. This review summarizes the molecular mechanisms involved in osseointegration, analyzes preclinical and clinical evidence on nutraceuticals, and critically assesses their translational potential. These compounds promote osteoblastogenesis, inhibit osteoclast differentiation, and mitigate oxidative stress, thereby improving peri-implant bone stability. Despite encouraging results, the clinical translation of nutraceuticals remains limited. Most available data are preclinical or based on surrogate endpoints such as bone mineral density, whereas true clinical success is determined by bone-to-implant contact and implant survival, which are rarely investigated in randomized controlled trials (RCTs). Advances in bioavailability strategies (liposomes, nanoemulsions, nanostructured lipid carriers) may improve systemic exposure, but future research must standardize dosages and provide high-quality RCTs to clarify the role of nutraceuticals as complementary tools in orthopedic implant surgery.
Association between systemic redox balance and osteoporosis: prospective evidence, polygenic modification, and proteomic and inflammatory mediation in the UK Biobank.
Zhu Y, Liu D, Yin X … +2 more , Zhang TJ, Wu N
Bone · 2026 Apr · PMID 41570964 · Publisher ↗
PURPOSE: Redox signaling governs bone remodeling, but whether systemic redox balance is associated with incident osteoporosis, genetic susceptibility, and proteomic/inflammatory pathways at population scale remains uncle...
PURPOSE: Redox signaling governs bone remodeling, but whether systemic redox balance is associated with incident osteoporosis, genetic susceptibility, and proteomic/inflammatory pathways at population scale remains unclear. METHODS: We analyzed UK Biobank participants free of osteoporosis at baseline. Serum redox balance score (SRBS) combined albumin, total bilirubin, and γ-glutamyl transferase. Cox proportional hazards models adjusted for prespecified covariates. Effect modification by an osteoporosis polygenic risk score (PRS) was tested on multiplicative and additive scales. Mediation was evaluated in a proteomics subset and an inflammatory-panel subset using counterfactual mediation with multiple-testing control. RESULTS: Over a median follow-up of 12.8 years (IQR, 11.7-13.7), 12,893 incident osteoporosis cases were observed. SRBS demonstrated a nonlinear inverse association with osteoporosis, displaying a J-shaped pattern: relative to Q1, multivariable hazard ratios (95% CIs) were 0.82 (0.78-0.86) for Q2, 0.75 (0.71-0.78) for Q3, and 0.72 (0.68-0.75) for Q4; the per-standard-deviation increase corresponded to an HR of 0.85 (0.83-0.87). Cumulative-incidence curves diverged early and showed a stepwise gradient across quartiles. Associations were stronger among men and physically inactive participants. SRBS interacted with the osteoporosis PRS on the multiplicative scale (interaction HR, 1.03; 95% CI, 1.02-1.04), whereas evidence for additive interaction was limited. Proteomic mediation implicated EGFR, TNFRSF10A, CBLN4, CD27, and IGDCC4 (≈8-11% each); inflammatory mediation implicated C-reactive protein (≈8%), platelets (≈4%), and neutrophils (≈4%). CONCLUSION: Systemic redox balance values were linked to osteoporosis risk, with partial mediation through plasma-protein and inflammatory pathways and only modest modification by polygenic risk.
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