G protein-coupled receptors (GPCRs), commonly known as seven-transmembrane domain receptors, represent one of the largest and most functionally diverse families of membrane receptors. These receptors mediate cellular responses to external signals, thereby influencing various physiological processes. Recent studies have increasingly highlighted the importance of GPCRs in skeletal health, particularly in regulating bone metabolism and the pathogenesis of bone diseases, such as osteoporosis and osteoarthritis. Among GPCRs, a specific subset that responds to fatty acids, including GPR40, GPR120, GPR41, GPR43, GPR84, and GPR119, has received significant attention for its role in skeletal homeostasis. Acting as lipid sensors, these receptors detect changes in fatty acid availability and transduce signals that modulate the differentiation, function, and survival of key bone cell populations, including osteoclasts, osteoblasts, and chondrocytes. This review provides a comprehensive overview of the current understanding of fatty acid-sensing GPCRs in skeletal metabolism, highlighting their potential as novel therapeutic targets for metabolic bone diseases.

Background: Although various surface modifications enhance titanium (Ti) implant osseointegration, achieving rapid bone formation comparable to native healing remains challenging. Current strategies primarily focus on micro-scale topography, often overlooking the critical role of macroscopic three-dimensional (3D) architecture in osteoconduction. Methods: We hypothesized that mimicking native bone’s porous architecture is key to accelerating osseointegration. First, we verified the impact of structural continuity by comparing standard Ti implants with decellularized bone grafts in a mouse calvaria defect model. Subsequently, we developed a biomimetic polycaprolactone (PCL)-based 3D architectural cover (Cover-type) and evaluated its osseointegration efficacy in a rat femur model against conventional Ti implants. Results: The mouse study confirmed that decellularized bone integrated significantly faster than Ti, highlighting the necessity of 3D continuity. In the rat model, micro-computed tomography analysis indicated a clear trend of increased bone formation in the Cover-type group, though statistical significance was limited by sample size. However, histological analysis confirmed a statistically significant enhancement in bone-to-implant contact compared to controls (P<0.05). The PCL structure served as a scaffold for cell migration, effectively bridging the implant-bone gap. Conclusions These findings suggest that providing a bone-like 3D environment via a PCL cover may enhance histological osseointegration, rather than relying solely on surface chemistry.

Background: This study aimed to investigate the densitometric characteristics and qualitative bone status in patients with normocalcemic primary hyperparathyroidism (PHPT) compared with those in controls who were younger adults under 50 years. Methods: This retrospective study included 60 controls and 31 patients with PHPT who underwent dual energy X-ray absorptiometry (DXA) of the lumbar spine (LS), femoral neck (FN), and total hip (TH). Trabecular bone score (TBS) was derived from LS DXA images. Bone mineral density (BMD) values were assessed using Z-scores, and correlations between TBS, BMD, and laboratory parameters were examined. Results: The median ages of the control and PHPT groups were 41 and 42 years, respectively. The proportion of individuals classified as “below the expected range for age” based on Z-scores differed significantly between groups only when considering any site collectively. Median TBS was significantly lower in PHPT patients than in controls, even when BMD values at LS, FN, and TH fell within similar diagnostic categories. In controls, TBS and BMD demonstrated very low correlation coefficients. In contrast, PHPT patients showed a stronger correlation between TBS and femoral BMD, whereas the association between TBS and LS BMD was largely absent. Among laboratory markers, only serum intact parathyroid hormone was significantly negatively correlated with TBS. Conclusions Young adults with PHPT exhibit impaired bone quality despite relatively preserved BMD, suggesting early microarchitectural deterioration. These findings support the combined use of LS and femoral BMD with TBS for more accurate assessment of skeletal health in PHPT.

Background: Bone morphogenetic protein (BMP) signaling is crucial for osteogenic (OS) differentiation, bone growth, and repair. However, the clinical use of BMPs is limited due to their cost and challenges in delivery. SB4, a potent compound of benzoxazole, is a newly introduced small molecule shown to activate the BMP signaling pathway. In this study, we investigated the effects of SB4 on OS differentiation of adipose-derived mesenchymal stem cells (ADMSCs). Methods: We first examined whether BMP signaling is active in osteoinduced ADMSCs. ADMSCs were treated with SB4 (5 and 10 μM) for 24 hr, and mRNA expression of BMP direct target genes (ID1 and ID3) was analyzed. ADMSCs were then cultured with or without SB4 (10 μM) for 7, 14, and 21 days, followed by Alizarin red staining and real-time polymerase chain reaction analysis of mRNA expression of OS markers RUNX2, BMP2, alkaline phosphatase (ALP), and Osteopontin. To investigate the most effective time period of SB4 in osteogenesis, SB4 was applied every 3.5 days during the 21-day differentiation period. Results: After 24 hr of treatment with SB4 (5 and 10 μM), increased mRNA expression of BMP direct target genes (ID1 and ID3) confirmed that SB4 acts as an active BMP agonist. SB4-treated ADMSCs showed enhanced bone matrix production and increased mRNA expression of RUNX2, BMP2, ALP, and Osteopontin. Increased mRNA expression of OS markers, bone matrix formation, and ALP activity during the first 7 days of SB4 treatment suggested the importance of SB4 at the early stage of differentiation. Conclusions These results indicate that SB4, with potential BMP-like activity, induces OS differentiation of ADMSCs, leading it to serve as a cost-effective BMP agonist for osteogenesis-related research as well as a potential therapeutic agent for bone repair and regeneration.

Background: Osteoporosis is consistently reported to increase mortality risk in older adults. Whether trabecular bone score (TBS), an indirect index of trabecular microarchitecture, increases mortality risk has not been widely studied. Methods: Participants aged 60 years and older in the National Health and Nutritional Examination Survey 2005 to 2008 with complete data on TBS lumbar vertebrae were linked to the public-use mortality files through December 31st, 2019. The X-tile software (version 3.6.1; Yale University) was used to obtain the overall and sex-specific optimal TBS cut-off values associated with all-cause mortality (log-rank test P<0.0001). Then, TBS was grouped into low (≤1.24), medium (1.25-1.39), and high (≥1.40) categories. Results: A total of 2,641 participants with a mean age of 69.8 (standard error 0.2) years comprised the study sample. Of those, 1,109 older adults died after a median follow-up of 140 months. Overall, survival probability progressively decreased across TBS categories, which was accentuated in subjects with low TBS. Cox regression analysis demonstrated that participants with low TBS had 47% (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.10-1.96) greater all-cause mortality risk than their counterparts with high TBS, even after accounting for potential confounders including bone mineral density. Notably, older adults with low TBS had 2-fold higher risk of cancer-related mortality than those with high TBS (HR, 2.07; 95% CI, 1.17-3.67). Conclusions Low TBS was significantly associated with greater all-cause and cancer-related mortality in older adults.

Background: Fall risk assessment and preventive interventions are important for preventing secondary fractures after hip fracture. The aim of this study was to investigate the distribution and characteristics of Fall Risk Index-21 (FRI-21) scores based on prefracture living conditions in patients with fall-related unilateral hip fracture. Methods: This study included 95 people who had suffered a hip fracture after a fall and had undergone surgery. FRI-21, dual energy X-ray absorptiometry (DXA), and hip structure analysis/trabecular bone score based on DXA were performed within 1 week after surgery. We compared bone parameters between the two groups, which were divided according to the cutoff value of the FRI-21. We also performed cluster analysis on the components of the FRI-21 and compared the characteristics of the subgroups via analysis of variance and multiple comparison tests. Results: All participants had experienced a fall-related fracture, but 47 (49.5%) of the patients were judged to have low scores (<10) on the FRI-21. Moreover, cluster analysis revealed that the subjects were classified into three subgroups, and the characteristics of the items that constitute fall risk, namely, physical function, disease or geriatric syndrome, and environmental factors, were diverse. Conclusions These results suggest that caution is needed when interpreting the FRI-21 total score based on preoperative living conditions in post-fracture patients, as it may not adequately reflect fall risk. Considering the characteristics of the FRI-21 score in patients with hip fractures, identifying appropriate fall prevention strategies and healthcare professionals involved may be important for preventing future re-fractures.

Background: Dual energy X-ray absorptiometry (DXA) measurements vary among instruments from different manufacturers. This study aimed to assess the correlation between bone mineral density (BMD) and body composition measured by the GE Lunar Prodigy and Hologic Horizon W DXA systems and to develop conversion equations. Methods: A total of 120 healthy volunteers (59 males, 61 females) aged 20 to 70 years were scanned on both DXA systems on the same day. BMD was measured at the lumbar spine (L1-L4) and bilateral femurs. Body composition parameters were measured for the whole body and regional sites. Bland-Altman analysis, Pearson correlation, and concordance correlation coefficient (CCC) were used to assess agreement. Linear regression was performed to derive conversion equations. Results: The Hologic system measured BMD values 14% to 20% lower at the lumbar spine and 8% to 17% lower at femoral sites compared to the GE Lunar system (all P<0.0001). Lean mass values were 4% to 10% lower on the Hologic system. Very strong correlations were observed for both BMD (r=0.944-0.980) and lean mass (r=0.963-0.984). Cross-calibration equations were developed for all measurement sites. Conclusions Despite significant systematic differences, there was very high correlation between the two DXA systems. The conversion equations can facilitate comparison of measurements between these systems in clinical practice and research.

Background: To investigate the fracture risks associated with anti-diabetic drugs in older women with type 2 diabetes mellitus (T2DM), who are particularly susceptible to skeletal fragility. Methods: Using data from the Korean National Health Insurance Service, this nested case-control study included 10,104 older women with T2DM and osteoporotic fractures (aged 66.5±3.4 years) matched in a 1:3 ratio with controls by birthdate, Charlson Comorbidity Index, and cohort entry date. We analyzed the odds of major osteoporotic fracture (MOF), vertebral fracture (VF), and non-VF (NVF) in users of sulfonylurea, thiazolidinedione (TZD), dipeptidyl peptidase-4 inhibitor, and sodium-glucose cotransporter 2 inhibitor (SGLT2i), compared to metformin (Met)-only users using multivariable logistic regression. Results: During a follow-up period of 3.8±2.8 years, TZD users had a higher risk of MOF than Met-only users (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.19-1.53; P<0.001). Risks of VF and NVF were also increased in the TZD group (OR, 1.21; 95% CI 1.03-1.42; P=0.022 and OR, 1.32; 95% CI 1.14-1.52; P<0.001, respectively). No significant differences were observed in other drug groups. The increased risk of VF and NVF in the TZD group were particularly pronounced in patients with normal or osteopenic bone mineral density (BMD) and in those with normal body mass index (BMI), respectively. Conclusions In older women with T2DM, TZD use was associated with increased VF and NVF risks, particularly among those with normal or osteopenic BMD and normal BMI. SGLT2i showed no increased risk, but further large-scale studies are needed to confirm its skeletal safety.

Background: Osteoporosis is a major global health concern, affecting over 200 million individuals worldwide. Although numerous clinical and experimental studies exist, comprehensive analyses integrating fracture-related and drug-specific research remain limited. Examining global research trends can highlight evolving themes, key contributors, and areas requiring scientific attention. Methods: We performed a bibliometric analysis of literature on osteoporosis and fractures, including drug-specific terms (denosumab, romosozumab, teriparatide), published between 2015 and 2025 in the Scopus Core Collection. Data were assessed for publication trends, authorship, institutional output, international collaboration, and thematic evolution using Bibliometrix-Biblioshiny in RStudio. Network analyses included co-authorship and keyword co-occurrence mapping for both quantitative and qualitative insights. Results: From 4,450 articles, annual output showed steady growth, peaking between 2021 and 2024. The United States, Japan, and China led in publication volume and citation impact, while Osteoporosis International was the most productive journal. Citation averages declined recently due to lag in newer publications. Thematic mapping identified pharmacological therapies such as denosumab and teriparatide as core themes, while “fracture prevention” and “DXA-based assessment” emerged as active research fronts. International collaboration decreased after 2020, particularly affecting contributions from low- and middle-income countries. Conclusions Global osteoporosis research demonstrates sustained productivity but declining collaboration and limited thematic diversification. Strengthening international networks, supporting underrepresented regions, and expanding focus to preventive and non-pharmacological strategies are essential for equitable and impactful progress.

This review aims to synthesize current knowledge regarding the use of bisphosphonates (BPs) in the treatment of bone complications in patients with neurofibromatosis type 1 (NF1). NF1 is a genetic disorder marked by multiple benign tumors of the nervous system and various skeletal abnormalities, such as osteoporosis and an increased risk of fractures. BPs are drugs that inhibit bone resorption, commonly used to treat osteoporosis and other bone diseases. The review identified multiple studies examining the effects of BP therapy in NF1 patients. Most studies reported improvements in bone mineral density and reduced fracture occurrence. The most commonly reported side effects were mild gastrointestinal symptoms and transient musculoskeletal pain. However, the evidence is limited by the small number of studies and the heterogeneity of patient populations and treatment protocols. In conclusion, BPs show improvements in managing NF1 complications such as osteoporosis and a reduction of fracture risk in NF1 patients. While the existing studies suggest positive outcomes, there is a need for more rigorous, large-scale studies to establish standardized treatment protocols and long-term safety profiles. Healthcare providers should consider BP therapy as a potential option for NF1 patients with significant bone complications, while also monitoring for possible adverse effects.