Xiong X, Huang H, Wang N
… +2 more, Zhou K, Song X
J Bone Miner Metab
· 2025 May · PMID 39786573
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INTRODUCTION: Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by an imbalance in chondrocyte metabolism. Ferroptosis has been implicated in the pathogenesis of OA. The role of Sirt1, a deacetyl...INTRODUCTION: Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by an imbalance in chondrocyte metabolism. Ferroptosis has been implicated in the pathogenesis of OA. The role of Sirt1, a deacetylase, in mediating deacetylation during ferroptosis in OA chondrocytes remains underexplored. This study aimed to elucidate the mechanisms by which Sirt1 influences chondrocyte ferroptosis in the development of OA. MATERIALS AND METHODS: In vitro and in vivo models of OA were established using IL-1β-induced mouse chondrocytes and a destabilization of the medial meniscus (DMM) mouse model, respectively. Ferroptosis was evaluated through measurements of cell viability, lactate dehydrogenase (LDH) release, intracellular levels of Fe2+, glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (ROS), propidium iodide staining, and Western blot analysis. The underlying mechanisms were further investigated using quantitative real-time polymerase chain reaction, Western blotting, immunoprecipitation (IP), co-immunoprecipitation (Co-IP), and glutathione-S-transferase pulldown assays. In vivo validation was performed via Safranin O staining. RESULTS: IL-1β induced ferroptosis and increased histone acetylation, effects that were partially reversed by Sirt1 overexpression. Mechanistically, Sirt1 overexpression upregulated ferritin light polypeptide (Ftl) expression by deacetylating Ftl at the K181 residue. Ftl knockdown inhibited the ferroptosis-enhancing effect of Sirt1 overexpression in chondrocytes. In vivo studies showed that Sirt1 overexpression mitigated the progression of OA and reduced ferroptosis in the DMM-induced OA mouse model. CONCLUSION: Our findings confirm that Sirt1 overexpression promotes Ftl expression through deacetylation at the K181 site, thereby suppressing chondrocyte ferroptosis and attenuating the progression of OA. These results suggest a potential therapeutic target for OA treatment.
Sugawara Y, Ishizu H, Arita K
… +8 more, Oue T, Sato K, Takahashi R, Kusunoki K, Shimodan S, Asano T, Iwasaki N, Shimizu T
J Bone Miner Metab
· 2025 May · PMID 39777540
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INTRODUCTION: Proximal femoral fractures are critically associated with increased risk of mortality and secondary fractures. Identifying prognosis predictors related to sagittal imbalance that are known to have negative...INTRODUCTION: Proximal femoral fractures are critically associated with increased risk of mortality and secondary fractures. Identifying prognosis predictors related to sagittal imbalance that are known to have negative impact on fracture risk and mortality is crucial. This study aimed to explore the relationship between various sagittal imbalance parameters and the prognosis of proximal femoral fractures to identify the most important prognostic indicators. MATERIALS AND METHODS: This multi-center prospective cohort study included patients with proximal femoral fractures treated surgically from April 2020 to March 2021. Spinal standing radiographs were obtained to measure various sagittal spine parameters. Postoperative follow-ups were conducted at 6, 12, 18, 24, and 36 months to assess mortality and secondary fracture rates and examine the predictors and their effects. RESULTS: Among the 137 patients who underwent spinal standing radiographs, 22 died and 23 developed secondary fractures. Multivariate analyses identified the number of previous vertebral fractures and thoracolumbar kyphosis (TLK) as significant risk factors for mortality and secondary fractures. Survival analysis revealed that patients with TLK < 20° had significantly higher survival rates than those with TLK ≥ 20° (P = 0.002 and P < 0.001 for mortality and secondary fractures, respectively). In addition, serum albumin was associated with mortality, and the intake of sleeping pills and antidepressants was associated with secondary fractures. CONCLUSION: TLK after surgery and the number of previous vertebral fractures affected both mortality and secondary fractures. When each risk factor, such as low serum albumin levels, intake of sleeping pills and antidepressants, was also considered, it was found that comprehensive postoperative care is essential.
Higuchi R, Uemura K, Kono S
… +7 more, Mae H, Takashima K, Abe H, Imagama T, Sakai T, Okada S, Hamada H
J Bone Miner Metab
· 2025 Mar · PMID 39656248
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OBJECTIVES: As many patients with osteoporosis remain undiagnosed, we aimed to develop a simple method to efficiently screen for osteoporosis using a combination of anteroposterior hip X-ray assessment and the Osteoporos...OBJECTIVES: As many patients with osteoporosis remain undiagnosed, we aimed to develop a simple method to efficiently screen for osteoporosis using a combination of anteroposterior hip X-ray assessment and the Osteoporosis Self-Assessment Tool for Asians (OSTA), which is calculated as (body weight - age) × 0.2. METHODS: One hundred Japanese women (age: 73 ± 11 years, body weight: 54.4 ± 11.1 kg) who underwent hip surgery, anteroposterior hip X-ray, and DXA were included. Based on the DXA results of the total proximal femur, 35 cases were diagnosed with osteoporosis. Fifteen orthopaedic surgeons visually inspected the hip X-ray images and scored the suspicion of osteoporosis on a scale of 1-4 (1: very unlikely, 4: very suspicious), which is referred to as "pred-score." In addition, OSTA was calculated as a continuous variable (OSTA score). Osteoporosis was screened using the pred-score and OSTA score, and both scores were analyzed using the receiver operating characteristic curves. RESULTS: The area under the curves (AUCs) of the pred-score and OSTA score were 0.626-0.875 and 0.817 across surgeons, respectively. When both scores were used, the AUC for screening osteoporosis ranged from 0.821 to 0.915 across surgeons. Significant improvement from AUCs calculated with the pred-score or OSTA score was found in 11 surgeons (73.3%). CONCLUSION: The combination of X-ray assessment and OSTA can be used to screen for osteoporosis and has the potential to be used as a new simple screening tool in daily clinical practice.
J Bone Miner Metab
· 2025 Jan · PMID 39645533
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INTRODUCTION: Romosozumab is an anti-sclerostin antibody drug with potent bone formation-promoting and bone resorption-inhibiting properties. It enhances bone mineral density and has a novel effect in preventing fracture...INTRODUCTION: Romosozumab is an anti-sclerostin antibody drug with potent bone formation-promoting and bone resorption-inhibiting properties. It enhances bone mineral density and has a novel effect in preventing fractures. However, there have been reports of non-responders to romosozumab. FINDINGS: If the least significant change is defined as 3%, only 2-12% of patients with spine osteoporosis are non-responders, and romosozumab is highly effective in this population. Low-type 1 amino-terminal propeptide (P1NP) levels during the early treatment phase are associated with non-responders early in treatment. The researchers found a cutoff value of 50.3 μg/L of P1NP in the first month of treatment. In contrast, hip osteoporosis does not respond (54-57% of the time). Low P1NP levels at the start of treatment increase the risk of non-responders. The cutoff value for P1NP was reported as 53.7 μg/L at the beginning of treatment. However, failure to meet these cutoff values does not necessarily indicate that the patient is a non-responder and does not justify a change in drug administration. CONCLUSIONS: In spine osteoporosis, romosozumab demonstrates high effectiveness, with approximately 2-12% of patients showing no response. However, in hip osteoporosis, approximately 54-57% do not respond to the treatment with romosozumab.
Shi G, Lin Z, Shen Q
… +7 more, Jin W, Hao Z, Wang J, Chen T, Chen J, Xin Wang, Li J
J Bone Miner Metab
· 2025 Mar · PMID 39641795
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INTRODUCTION: Previous research has demonstrated that even minor changes in thyroid function are associated with an increased risk of osteoporosis (OP). However, the causal relationship between thyroid disorders and the...INTRODUCTION: Previous research has demonstrated that even minor changes in thyroid function are associated with an increased risk of osteoporosis (OP). However, the causal relationship between thyroid disorders and the development of OP remains unclear. To address this, we aim to investigate the connection between genetic predispositions to various thyroid disorders and OP using a two-sample Mendelian randomization (MR) approach. MATERIALS AND METHODS: Instrumental variables (IVs) for multiple thyroid disorders were sourced from a large genome-wide association study (GWAS) meta-analysis dataset. Summary-level data for OP were obtained from the FinnGen consortium. Inverse variance weighting (IVW) methods served as the primary approach for MR analysis. Sensitivity analyses included MR-Egger regression, heterogeneity testing, multiple validity tests, and leaFve-one-out sensitivity tests. RESULTS: IVW analysis revealed a direct causal effect of hypothyroidism (OR = 1.105, 95% CI 1.023-1.194, P 0.011) and Hashimoto's thyroiditis (OR = 1.142, 95% CI 1.026-1.271, P 0.015) on OP. However, no direct causal association was found between hyperthyroidism (OR = 1.030, 95% CI 0.944-1.123, P 0.508) or thyroid cancer (OR = 0.971, 95% CI 0.898-1.051, P 0.469) and OP. CONCLUSION: Our MR analysis revealed a causal association between hypothyroidism, Hashimoto's thyroiditis, and OP. This highlights the significant impact of thyroid function on bone health. However, further longitudinal studies are needed to confirm these findings conclusively.
Hasegawa T, Yamamoto T, Haraguchi-Kitakamae M
… +11 more, Hongo H, Shi Y, Cui J, Liu X, Yao Q, Abe M, Maruoka H, Yokoyama A, Sekiguchi T, Makino A, Amizuka N
J Bone Miner Metab
· 2025 Jan · PMID 39630261
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Parathyroid hormone (PTH) is thought to induce remodeling-based bone formation by promoting osteoclastic activity, a process known as cellular coupling. Our research has shown that the frequency of PTH administration aff...Parathyroid hormone (PTH) is thought to induce remodeling-based bone formation by promoting osteoclastic activity, a process known as cellular coupling. Our research has shown that the frequency of PTH administration affects trabecular number and thickness. High-frequency PTH administration induced remodeling-based bone formation, while less frequent administration induced both remodeling-based and modeling-based bone formation. Additionally, we found that specific bone sites influence whether remodeling-based or modeling-based bone formation is more likely to occur. Additionally, while PTH significantly increases trabecular bone, it also causes cortical porosis. Our research on the femoral diaphysis showed that PTH administration resulted in the invasion of blood vessels and osteoclasts into the cortical bone. Abaloparatide acts similarly to teriparatide through the parathyroid hormone receptor type 1 (PTH1R) but may have a wider anabolic window due to its lesser impact on bone resorption. Our mouse studies with abaloparatide showed similar results to those seen in human patients, with increased preosteoblastic cell populations and wider anabolic windows when compared with teriparatide. Abaloparatide-induced bone formation cannot be explained solely by remodeling-based bone formation, indicating the need for further research into modeling-based bone formation.
J Bone Miner Metab
· 2025 Mar · PMID 39623083
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BACKGROUND: The fibula, situated laterally in the leg, receives vital nutrition through nutrient arteries during embryonic bone growth and early ossification. This study aims to assess the direction, distance, location,...BACKGROUND: The fibula, situated laterally in the leg, receives vital nutrition through nutrient arteries during embryonic bone growth and early ossification. This study aims to assess the direction, distance, location, number, and foraminal index of nutrient foramina in dry fibulae from the South Indian population. MATERIALS AND METHODS: A descriptive cross-sectional analysis involved 63 dry adult human fibulae sourced from the Department of Anatomy, Saveetha Medical College and Hospital, Thandalam. Parameters like fibula length, location, number, and direction of vascular foramina were recorded. Statistical analyses were performed on morphometric data and foraminal index. RESULTS: The mean fibula length was 34.68 ± 2.11 cm. Among the fibulae, 88.88% had a single nutrient foramen, 4.76% had dual foramina, and 6.34% lacked nutrient foramina. Most single foramina were found on the medial crest (66.66%), followed by between the medial crest and posterior border (20.63%). Nutrient foramina were primarily located in Zone II (87.30%), followed by Zone III (11.11%) and Zone I (1.58%). Directionally, 85.71% pointed downward, while 14.28% pointed upward. The mean foraminal index was 40.85 ± 6.78, ranging from 32.57 to 56.25. CONCLUSION: Zone II, particularly on the medial crest, was the most prevalent location for vascular foramina in the fibula. Dual foramina occurred in 6.34% of cases. This precise anatomical knowledge is valuable for various medical professionals, including anthropologists, forensic experts, radiologists, plastic surgeons, and orthopedic surgeons, especially in procedures involving vascularized fibular bone grafts.
Erdoğan K, Kara M, Şener FE
… +7 more, Durmuş ME, Durmuşoğlu BNÇ, Abdulsalam AJ, Sezer S, Kara Ö, Kaymak B, Özçakar L
J Bone Miner Metab
· 2025 Mar · PMID 39516399
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INTRODUCTION: To explore the possible associations between blood markers including albumin, hemoglobulin, creatinine and 25 OH vitamin D with sarcopenia using the ISarcoPRM algorithm. MATERIALS AND METHODS: A total of 20...INTRODUCTION: To explore the possible associations between blood markers including albumin, hemoglobulin, creatinine and 25 OH vitamin D with sarcopenia using the ISarcoPRM algorithm. MATERIALS AND METHODS: A total of 2094 community-dwelling males and postmenopausal females (495 males, 1599 females)aged ≥ 50 years were recruited and their demographic data along with all comorbidities and laboratory evaluations were noted. Functional measurements were also quantified and the ISarcoPRM algorithm was used for the diagnosis/confirmation of the participants into sarcopenic and non-sarcopenic categories. RESULTS: Sarcopenia was detected in 434 (20.7%) participants and low albumin level in 578 (27.6%) of them. While sarcopenia was detected in 193 (33.4%) of 578 subjects with low albumin levels, and in 241 (15.9%) of 1516 subjects with normal albumin levels (p < 0.001). In the binary logistic regression analysis, among the blood parameters; only albumin levels [OR: 0.932 (95% CI 0.876-0.992) in males (p = 0.026), OR: 0.901 (95% CI 0.862-0.941) in females (p < 0.001)were found to be independently associated with sarcopenia in each gender. After adjusting for sociodemographic and other clinical factors, having low albumin levels(≤ 4.0 g/dL) were independently associated with sarcopenia i.e. 2.368 times (95% CI 1.424-3.939) in males and 2.026 times (95% CI 1.520-2.699) in females (both p < 0.001). CONCLUSION: Independent of other factors, low albumin level is associated with sarcopenia i.e. at least two times in both genders. Older and obese adults at risk of malnutrition should be screened/diagnosed and treated early for sarcopenia. Prospective studies are needed for better/prompt management of relevant patients who are prone to significant morbidity and mortality.
Sawamura K, Matsushita M, Esaki R
… +5 more, Mishima K, Kamiya Y, Ohno K, Kitoh H, Imagama S
J Bone Miner Metab
· 2025 Mar · PMID 39514089
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INTRODUCTION: Achondroplasia (ACH) is a common skeletal dysplasia associated with short-limbed short stature caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Meclozine was fou...INTRODUCTION: Achondroplasia (ACH) is a common skeletal dysplasia associated with short-limbed short stature caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Meclozine was found to inhibit FGFR3 signaling using a drug repositioning strategy. In some countries, growth hormone (GH) has been employed to ameliorate short stature in children with ACH. This study aims to investigate the effects of meclozine and GH on bone growth and quality using an experimental model of ACH. MATERIALS AND METHODS: Meclozine (2 mg/kg/day) and/or GH (0.35 mg/kg/day) were administered to a mouse model of ACH from the age of 7 to 56 days. Body length and body weight of each mouse were measured during these treatments. At the end of treatments, these mice were subjected to micro-computed tomography scans to measure the lengths of long bones and bone mineral density (BMD). The width of the growth plate was quantified by histological analysis. RESULTS: The body and bone length of transgenic mice significantly increased after treatment with meclozine and GH, although there was no additive effect of the combination therapy on promoting bone growth. In contrast, BMD was additively increased by the combination therapy. The width of the growth plate in transgenic mice was significantly increased by both treatments, although the hypertrophic zone was enlarged by meclozine but not by GH. CONCLUSION: Meclozine or GH may be an option for treating children with ACH to ameliorate bone length and quality, but the additive effect would be limited.
Mori Y, Tarasawa K, Tanaka H
… +4 more, Mori N, Fushimi K, Aizawa T, Fujimori K
J Bone Miner Metab
· 2025 Mar · PMID 39510991
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INTRODUCTION: The risk of postoperative sequelae and in-hospital mortality in Japanese patients aged 90 years and older with hip fractures is unexplored. This study aims to use a comprehensive medical claims database in...INTRODUCTION: The risk of postoperative sequelae and in-hospital mortality in Japanese patients aged 90 years and older with hip fractures is unexplored. This study aims to use a comprehensive medical claims database in Japan to compare super-elderly patients aged 90 years and older with elderly aged 65-89 and clarify the risk of sequelae and in-hospital mortality in super-elderly patients. MATERIALS AND METHODS: We retrospectively analyzed the Diagnosis Procedure Combination (DPC) database for all of Japan from April 2016 to March 2022. Medical records from approximately 1100 DPC-related hospitals were provided with consistent consent during this period. In this study, we focused on super-elderly patients and examined the association with the risk of postoperative pneumonia, pulmonary embolism, myocardial infarction, urinary tract infection, acute renal dysfunction, subsequent cognitive dysfunction, and in-hospital mortality after one-to-one propensity score matching. RESULTS: After performing propensity score matching based on sex and comorbidities, 129,953 pairs of patients were identified. These pairs were compared to elderly and super-elderly patients. The results of this study showed that compared with hip fractures in the elderly, hip fractures in the super-elderly were associated with an increased risk of pneumonia, urinary tract infection, acute renal dysfunction, subsequent cognitive dysfunction, and in-hospital mortality after adjustment for confounders. The odds ratio of in-hospital mortality was 2.190 (95% CI 2.062-2.325). CONCLUSION: As it has been shown that super-elderly patients with hip fractures are at greater risk of respiratory and urinary tract infections and increased in-hospital mortality, careful attention should be required for perioperative management.
Silva FF, Lima ML, Pedreira CC
… +1 more, Matos MA
J Bone Miner Metab
· 2025 Mar · PMID 39508862
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INTRODUCTION: The purpose of this study was to evaluate the impact of disease activity and gonadal status on bone mineral density (BMD) and turnover markers (BTMs) in individuals with acromegaly. MATERIALS AND METHODS: S...INTRODUCTION: The purpose of this study was to evaluate the impact of disease activity and gonadal status on bone mineral density (BMD) and turnover markers (BTMs) in individuals with acromegaly. MATERIALS AND METHODS: Subjects underwent laboratory tests for PTH, 25-hydroxyvitamin D, calcium, phosphorus, osteocalcin (OC) and C-telopeptide (CTX-1) and bone densitometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH). RESULTS: Sixty participants (48.6 ± 11.0 years; 66,7% female) were included in this cross-sectional study. Phosphorus, OC, CTX-1, and LS BMD were greater in the active disease group than in the controlled/cured disease group (P = 0.025, P < 0.001, P = 0.007, and P = 0.016, respectively). When analyzing gonadal status, phosphorus, OC and CTX-1 were greater in the hypogonadal group than in the eugonadal group (P = 0.017, P = 0.015, and P = 0.033, respectively). Patients with hypogonadism had a higher prevalence of reduced bone mass compared to eugonadal patients (44 vs. 17%, P = 0.023). CONCLUSION: This study revealed increased levels of phosphorus and BTMs in patients with active acromegaly. In this group, the greater LS BMD values are likely due to the anabolic effects of GH and IGF-1 and/or to the influence of LS arthropathy. Moreover, hypogonadism negatively impacts bone metabolism in acromegaly, leading to elevated BTMs and a higher prevalence of reduced bone mass in individuals affected by both conditions.
Kuba S, Chiba K, Watanabe K
… +13 more, Matsumoto M, Morita M, Akashi M, Yukutake A, Hara Y, Fukushima A, Inamasu E, Otsubo R, Yamanouchi K, Kanetaka K, Osaki M, Matsumoto K, Eguchi S
J Bone Miner Metab
· 2025 Mar · PMID 39508861
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INTRODUCTION: Aromatase inhibitors (AIs) are the standard treatment for early breast cancer (EBC) and are typical causative agents of cancer treatment-induced bone loss. However, the effects of long-term treatment with t...INTRODUCTION: Aromatase inhibitors (AIs) are the standard treatment for early breast cancer (EBC) and are typical causative agents of cancer treatment-induced bone loss. However, the effects of long-term treatment with these drugs on bone microstructure remain unclear. MATERIALS AND METHODS: This prospective, single-arm observational study included postmenopausal, non-osteoporotic women with hormone receptor-positive EBC. Patients who underwent dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type I N-terminal propeptide levels were compared at baseline and at 60 months after commencing AI treatment. RESULTS: Fifteen women were included in the study, with a median age of 58 years and a quartile range of 56.5-62.5 years. At 60 months, HR-pQCT revealed that the cortical area and thickness decreased with increased cortical porosity in the cortical bone. In addition, the number of trabeculae decreased and trabecular separation increased trabecular bones decreases, and trabecular bone separation opens, resulting in a decrease in the trabecular bone volume fraction. Total bone mineral density (BMD), trabecular volumetric BMD, and cortical volumetric BMD, and estimated bone strength significantly decreased. DXA BMD values significantly decreased in the total hip and femoral neck but not the lumbar spine. TRACP-5b values after 5 years of AI treatment showed a significant negative correlation with the rate of change in the total volumetric BMD in the distal tibia. CONCLUSION: Postmenopausal women who received AIs for 5 years for EBC experienced significant deterioration in the bone microstructure, BMD, and estimated bone strength.
Huynh N, De Dios K, Tran TS
… +2 more, Center JR, Nguyen TV
J Bone Miner Metab
· 2025 Mar · PMID 39505754
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INTRODUCTION: Polymorphisms within the collagen 1 alpha 1 gene (COLIA1) have been shown to be associated with bone mineral density (BMD). This study aimed to test the hypothesis that COLIA1 polymorphisms are associated w...INTRODUCTION: Polymorphisms within the collagen 1 alpha 1 gene (COLIA1) have been shown to be associated with bone mineral density (BMD). This study aimed to test the hypothesis that COLIA1 polymorphisms are associated with bone loss and fragility fractures. MATERIALS AND METHODS: The study involved 809 postmenopausal women aged 60 years and above in the Dubbo Osteoporosis Epidemiology Study who had COLIA1 genotypes and at least two BMD measurements over a 30-year period. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) was measured biennially by dual-energy X-ray absorptiometry (GE-Lunar Prodigy). Fragility fracture has been ascertained by X-ray reports between 1990 and 2020. The G-> T polymorphism at the Sp1-binding site in the COLIA1 gene (rs1800012) was determined by the PCR-based method, and coded as GG, GT, and TT. RESULTS: Women homozygous for the minor allele (TT) tended to have greater bone loss (-0.72%/year) than those with GT (-0.58%/year) or GG (-0.56%/year) though the difference did not achieve statistical significance (P = 0.84). Women of the TT genotype were associated with a two-fold greater risk of any fracture (adjusted hazard ratio: 2.21; 95%CI 1.42-3.46) and almost fourfold greater risk of hip fracture (3.78; 1.83-7.82) than those with either GG or GT genotype. CONCLUSIONS: Polymorphisms at the Sp1 site in the COLIA1 gene are associated with fracture risk, independent of bone loss.
Fukui T, Terashima A, Omata Y
… +11 more, Chijimatsu R, Okamoto K, Tsukasaki M, Fukuda Y, Hayata T, Saitoh A, Toda E, Takayanagi H, Tanaka S, Terashima Y, Saito T
J Bone Miner Metab
· 2025 Mar · PMID 39373772
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INTRODUCTION: Disulfiram (DSF), known as an anti-alcoholism drug, has been reported to suppress osteoclast differentiation in vitro; however, it remains uncertain whether DSF is effective in preventing osteoclastogenesis...INTRODUCTION: Disulfiram (DSF), known as an anti-alcoholism drug, has been reported to suppress osteoclast differentiation in vitro; however, it remains uncertain whether DSF is effective in preventing osteoclastogenesis in vivo. This study aimed to investigate the effect of DSF administration in osteoporotic mice and its contribution to osteoclastogenesis in vivo. MATERIALS AND METHODS: The bone phenotype of ovariectomized mice, both treated and untreated with DSF, was examined using microcomputed tomography analysis. Osteoclastic and osteoblastic parameters were assessed through bone morphometric analysis. The direct effect of DSF on osteoblastogenesis in vitro was evaluated via a primary osteoblast culture experiment. The expression of genes related to DSF targets (Nup85, Ccr2, and Ccr5) in osteoclast-lineage cells was examined using scRNA-seq analysis and flow cytometry analysis using the bone marrow cells from ovariectomized mice. The impact of DSF on osteoclast-lineage cells was assessed using primary cultures of osteoclasts. RESULTS: DSF administration ameliorated ovariectomy-induced bone loss and mitigated the increase of osteoclasts without affecting osteoblastogenesis. The scRNA-seq data revealed that osteoclast precursor cells expressed Nup85, Ccr2, and Ccr5. CCR2 and CCR5-positive cells in osteoclast precursor cells within bone marrow increased following ovariectomy, and this increase was canceled by DSF administration. Finally, we found that DSF had a significant inhibitory effect on osteoclastogenesis in the early stage by suppressing Tnfrsf11a expression. CONCLUSION: This study demonstrates that DSF could be a candidate for osteoporosis therapies because it suppresses osteoclastogenesis from an early stage in vivo.
J Bone Miner Metab
· 2025 Jan · PMID 39352550
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Hedgehog and canonical Wnt signaling pathways and the transcription factors Runx2 and Sp7 are essential for osteoblast differentiation. Ihh is necessary for the commitment of perichondrial mesenchymal cells to Runx2 oste...Hedgehog and canonical Wnt signaling pathways and the transcription factors Runx2 and Sp7 are essential for osteoblast differentiation. Ihh is necessary for the commitment of perichondrial mesenchymal cells to Runx2 osteoprogenitors and for the formation of the bone collar and primary spongiosa. Runx2 is needed for osteoblast differentiation during both endochondral and intramembranous ossification. It regulates the commitment of mesenchymal cells to osteoblast-lineage cells and their proliferation by inducing the expression of Hedgehog, Fgf, Wnt, Pthlh signaling pathway genes, and Dlx5. The Runx2-induced expression of Fgfr2 and Fgfr3 is important for the proliferation of osteoblast-lineage cells. Runx2 induces Sp7 expression and Runx2 osteoprogenitors become Runx2Sp7 preosteoblasts. Runx2, Sp7, and canonical Wnt signaling induce the differentiation of preosteoblasts into osteoblasts. Canonical Wnt signaling, but not Sp7, enhances the proliferation of osteoblast-lineage cells. In mature osteoblasts, Runx2 plays an important role in the expression of major bone matrix protein genes, including Col1a1, Col1a2, Spp1, Ibsp, and Bglap/Bglap2. The canonical Wnt signaling pathway is also crucial for bone formation by mature osteoblasts. Sp7 is needed for osteocytes to acquire a sufficient number of processes and a reduction in these processes results in osteocyte apoptosis and cortical porosity.
J Bone Miner Metab
· 2025 Mar · PMID 39349871
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INTRODUCTION: The association between serum vitamin D levels and bone mineral density (BMD) varies by race and gender. This study aimed to evaluate this relationship between serum vitamin D levels and BMD, and changes of...INTRODUCTION: The association between serum vitamin D levels and bone mineral density (BMD) varies by race and gender. This study aimed to evaluate this relationship between serum vitamin D levels and BMD, and changes of BMD over time in Korean women. MATERIALS AND METHODS: We analyzed data from 586 generally healthy Korean women aged 29-79 who underwent health check-ups at Seoul National University Gangnam Center between 2010 and 2011 (baseline measurement) and 2015-2016 (follow-up). Dual energy X-ray absorptiometry (DEXA) and serum 25-hydroxyvitamin D (25OH-D) level measurements were conducted. We assessed the association between serum 25OH-D levels and BMD, as well as changes in BMD over time. RESULTS: The mean age of participants was 51.3 ± 7.9 years, with a mean follow-up interval of 4.6 ± 0.7 years, and mean serum 25OH-D level of 20.6 ± 8.5 ng/ml. Baseline serum 25OH-D levels did not correlate with BMD values at the lumbar spine, femoral neck, or total femur, nor with changes in BMD over time. A significant negative association was found between perimenopausal status and BMD changes at all sites, and between premenopausal status and lumbar bone mass, compared to postmenopausal status in the 25OH-D < 20 ng/ml group. This association was not observed in women with higher serum 25OH-D levels. CONCLUSIONS: Serum 25OH-D levels did not correlate with BMD levels or changes in BMD overall. However, in late reproductive-aged and perimenopausal women with serum 25OH-D insufficiency, there was a significant association with accelerated bone loss.
Baek HS, Shin K, Kim J
… +5 more, Jeong C, Lee J, Lim Y, Baek KH, Ha J
J Bone Miner Metab
· 2024 Nov · PMID 39349870
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INTRODUCTION: Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CT...INTRODUCTION: Chemotherapy-induced bone loss (CTIBL) is common among breast cancer patients, requiring comprehensive assessment and intervention. Zoledronic acid, a strong inhibitor of bone resorption, is effective in CTIBL management, though information on dosing and intervals, particularly the efficacy of the 5 mg annual dose for osteoporosis in breast cancer patients, is limited. MATERIALS AND METHODS: In this 12-month prospective observational study, 85 breast cancer patients were divided into three groups: 17 received no treatment, 17 received tamoxifen, and 51 received anastrozole or letrozole (AI). Post-surgery, patients were administered a single 5 mg dose of zoledronic acid and monitored over 12 months for changes in bone mineral density (BMD), fracture rates, and biochemical markers. RESULTS: Initially, the AI group was the oldest, averaging 59.1 ± 8.7 years. At baseline, no significant differences in variables, except age, were observed. After 12 months, BMD increased in all groups following a single zoledronic acid dose, with the smallest increase in the AI group at the lumbar spine: no treatment (2.4% ± 6.1%), tamoxifen (2.6% ± 3.4%), AI (0.6% ± 14.5%) (p = 0.778). CTx and P1NP levels were consistently suppressed up to 12 months post-treatment, with smaller reductions in the AI group. There were no significant differences in fracture or bone metastasis rates among groups. CONCLUSION: A single infusion of 5 mg zoledronic acid was effective in increasing bone density in breast cancer patients. However, AI-treated patients showed less improvement in vertebral bone mineral density and biochemical markers. Further long-term studies with larger cohorts are needed.
Tang Y, Xu Y, Song J
… +4 more, Zhang C, Tian R, Wang K, Yang P
J Bone Miner Metab
· 2024 Nov · PMID 39325234
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OBJECTIVE: This study aimed to estimate the relation between cigarette smoking and hip fracture in men compared with women using a meta-analytic approach. METHODS: On March 1, 2024, prospective cohort studies were search...OBJECTIVE: This study aimed to estimate the relation between cigarette smoking and hip fracture in men compared with women using a meta-analytic approach. METHODS: On March 1, 2024, prospective cohort studies were searched from PubMed, Embase and Cochrane library systems. The gender difference in the relationship between smoking and hip fracture risk was evaluated by random effect model. RESULTS: Eleven prospective cohort studies involving data from 2,689,620 individuals were selected for meta-analysis. The ratio of relative risk (RRR) of hip fractures in current smokers was significantly higher in men than in women (RRR: 1.10; 95%CI: 1.00 - 1.20; P = 0.047), while no evidence of sex differences in former smoking and hip fracture risk (RRR: 0.98; 95%CI: 0.88 - 1.10; P = 0.759). CONCLUSIONS: The male-to-female RRR of hip fractures increased in current smokers, whereas no sex difference was found in the relationship between former smoking and the risk of hip fractures.