Low birth weight (LBW) has been associated with impaired skeletal development and low peak bone mass. However, the association between LBW and fracture risk in postmenopausal women remains un-clear. We analyzed prospectively collected data from the population-based Osteoporosis Risk Factor and Pre-vention (OSTPRE) cohort, including women aged >50 years. Birth weight was categorized as LBW (<2500 g) or normal birth weight (≥2500 g). Fracture outcomes were analyzed using standardized inci-dence ratios (SIRs) with 95
Bone formation begins with the establishment of a tissue called osteoid, traditionally described as unmineralized. Despite extensive research on bone, this primary tissue remains surprisingly understudied, as reflected by the very limited number of reviews dedicated to it. Current understanding largely relies on data from diverse experimental models, ranging from human bone to calcified chicken tendon, and spanning different stages of development (from embryo to adult), although bone structure and formation vary across these systems. At the crossroads of multiple disciplines, osteoid description also depends on the techniques used in a research field, such as histological stains or transmission electron microscopy, which probe very different length scales. Over time, findings have been combined and extrapolated, often without direct evidence in humans. This review emphasizes the importance of osteoid by critically evaluating the existing literature. It aims to integrate current knowledge of processes occurring in osteoid, from collagen fibrillogenesis to the mineralization front, and to provide a renewed perspective on a tissue whose structure and composition are crucial for establishing the scaffold for mature healthy bone. Revisiting osteoid tissue characteristics should deepen our understanding and inspire new approaches to bone diagnosis.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of long-term use of anti-resorptive agents, particularly with the nitrogen-containing bisphosphonate zoledronic acid (ZOL), and is characterized by exposed necrotic jawbone. Although pro-inflammatory macrophage polarization contributes to MRONJ progression, the molecular mechanisms governing ZOL-induced polarization remain incompletely understood. Protein sorting and degradation fundamentally regulate macrophage functional phenotypes. Here, we identified signal transducing adaptor molecule 2 (Stam2), a component of endosomal sorting complex required for transport (ESCRT), as the most markedly upregulated ESCRT subunit in ZOL-induced pro-inflammatory macrophages. In a murine MRONJ model, myeloid-specific Stam2 deficiency significantly attenuated osteonecrosis, reduced pro-inflammatory macrophage infiltration, and enhanced angiogenesis within extraction sockets. Furthermore, genetic ablation of Stam2 in macrophages suppressed ZOL-driven pro-inflammatory polarization while decreasing NF-κB signaling activation. Collectively, these findings identify myeloid Stam2 as a key regulator of ZOL-induced pro-inflammatory responses and MRONJ progression.
Vertebral fragility fractures (VFF) are associated with pain, impaired function, and increased fracture risk. Our aim was to develop an internationally applicable model to guide the care of individuals with VFF. The Fragility Fracture Network (FFN) VFF Special Interest Group established the project structure and scope: review existing guidance and adapt recommendations and a visual model; solicit knowledge user feedback; make iterative revisions to the recommendations and visual model based on feedback; and finalize the recommendations. The model adapts recommendations from a published international Delphi consensus and national guidance. Knowledge user feedback was obtained through a survey disseminated via FFN channels across 40 countries. The survey responses informed iterative revision and finalization of the care model. The final VFF care model comprised three domains. ‘Pain management’ emphasizes structured pain and physical functioning assessment, multimodal pharmacological and non-pharmacological strategies, patient education, and timely referral for specialist review when indicated. The domain ‘Improving Physical Functioning’ included promoting movement, early mobilization, exercise focused on strength, balance, and back extensor endurance, and behaviour change approaches to support return to physical activities of leisure and daily living. The domain, Fall and Fracture Prevention, integrates falls and fracture risk assessment and prevention. It included nutritional evaluation, optimization of vitamin D and calcium intake, osteoporosis medication initiation, and referral for exercise, home hazard assessment, and specialist input. Cross-cutting components included patient education, behavioural support, and communication to ensure continuity of care. The VFF care model offers a comprehensive framework adaptable to diverse settings and an international perspective. Its multidisciplinary approach addresses gaps in VFF management and includes defined Key Performance Indicators. A multidisciplinary team developed an internationally applicable model to guide the care of individuals with vertebral fragility fracture, with input from knowledge users in 40 countries, with recommendations on pain management, improving physical functioning, and preventing falls and fractures.
Disuse osteoporosis induced by immobilization, bed rest, or spaceflight remains an inadequately treated condition. Whether local mechanical stimulation on a single limb can exert systemic anabolic effects during disuse, and whether such mechanotherapy is sex-dependent, are unknown. Here, male and female C57BL/6J mice (28-week-old) were assigned to ground control (GC) or 14-day hindlimb unloading (HU) groups. In both conditions, the left tibia received daily unilateral axial compressive loading, whereas the contralateral right tibia served as the non-loaded reference limb. Bone microarchitecture of both loaded and contralateral non-loaded tibiae was assessed using micro-computed tomography (micro-CT), while targeted analysis of hypothalamic–pituitary–gonadal (HPG)-associated and osteogenic genes was performed to investigate underlying molecular responses. Compared with GC, female HU mice had lower contralateral cortical thickness, cortical area, and trabecular bone volume fraction of the tibiae, whereas male HU mice had higher mean contralateral cortical thickness and cortical area. The findings revealed sex-associated differences in selected skeletal responses. In male HU mice, preservation of selected cortical and trabecular parameters was observed in both the loaded and contralateral non-loaded tibiae within the combined unloading and unilateral-loading paradigm. In contrast, female mice exhibited a different structural response pattern, with no comparable preservation of selected parameters in the contralateral non-loaded tibia. Gene expression analysis in male non-loaded tibiae demonstrated coordinated upregulation of HPG-associated and osteogenic genes, including NR5A1, LHR, FSHR, AR, BMP2, RUNX2, and TGF-β1, whereas the female RNA-seq analysis did not identify a comparable pattern of changes in the selected genes. The contralateral structural findings and accompanying transcriptional changes in male bone raise the possibility of systemic skeletal effects during combined unloading and unilateral loading. However, the study does not establish a systemic effect caused specifically by unilateral loading or demonstrate systemic HPG-axis activation. The results highlight the potential importance of sex-specific mechanobiological pathways in the development of therapeutic strategies for disuse osteoporosis.
