Bone Reports最新文献_第4页

Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease 1例儿童期低磷血症合并晚期慢性肾脏疾病的成人患者终生随访

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-08-18 DOI: 10.1016/j.bonr.2025.101872

Maria Sääf , Sigridur Björnsdottir , Mathias Haarhaus , Ellen-Margrethe Hauge , Diana Atanasova , Per Magnusson

Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism caused by mutations in the ALPL gene, resulting in deficient activity of tissue-nonspecific alkaline phosphatase and impaired skeletal mineralization. Affected individuals have a higher prevalence of chronic kidney disease (CKD) than the general population. We report a woman who underwent craniosynostosis surgery in infancy and lost her deciduous teeth prematurely. From age 27, she experienced recurrent foot pain due to multiple metatarsal fractures. Low levels of total alkaline phosphatase (ALP) was noted at 39 years of age, and low activities for the three bone-specific ALP (BALP) isoforms B/I, B1 and B2. Genetic analysis revealed 2 missense variants in the ALPL gene (p.Glu191Lys and p.Gly456Arg) confirming HPP. At age 44, she developed bilateral hip fissures requiring right-sided total hip replacement. Treatment with the parathyroid hormone analogue teriparatide (20 μg/day) was initiated at age 50, leading to increased BALP isoform levels indicating improved mineralization, less bone pain, and no new fractures during 9 months of treatment, which was stopped due to hypercalcemia and hyperphosphatemia. She began peritoneal dialysis at age 55 and received a kidney transplant at age 58. At age 65, seven years post-transplantation, she remained free of new fractures and significant bone pain. This case illustrates the long-term natural history of HPP with progressive skeletal complications across decades, and highlights the potential of short-term teriparatide as a therapeutic option for symptom relief and improved mineralization. It also suggests that kidney transplantation may contribute to improved bone health in HPP with advanced CKD.

低磷酸酶（HPP）是由ALPL基因突变引起的一种罕见的先天性代谢错误，导致组织非特异性碱性磷酸酶活性不足和骨骼矿化受损。受影响的个体有较高的患病率慢性肾脏疾病（CKD）比一般人群。我们报告一位妇女在婴儿期接受颅缝闭锁手术并过早失去乳牙。从27岁开始，由于多处跖骨骨折，她经历了反复的足部疼痛。39岁时总碱性磷酸酶（ALP）水平较低，三种骨特异性ALP （BALP）亚型B/I、B1和B2活性较低。遗传分析显示ALPL基因有2个错义变异（p.Glu191Lys和p.Gly456Arg），证实了HPP。44岁时，她出现双侧髋关节裂，需要右侧全髋关节置换术。50岁时开始使用甲状旁腺激素类似物特利帕肽（20 μg/天）治疗，导致BALP异构体水平升高，表明矿化改善，骨痛减轻，在9个月的治疗期间没有新的骨折，治疗因高钙血症和高磷血症而停止。她55岁开始腹膜透析，58岁接受肾移植。在65岁，移植后7年，她仍然没有新的骨折和明显的骨痛。本病例说明了HPP伴进行性骨骼并发症数十年的长期自然病史，并强调了短期使用特立帕肽作为缓解症状和改善矿化的治疗选择的潜力。这也表明肾移植可能有助于改善HPP合并晚期CKD患者的骨骼健康。

{"title":"Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease","authors":"Maria Sääf , Sigridur Björnsdottir , Mathias Haarhaus , Ellen-Margrethe Hauge , Diana Atanasova , Per Magnusson","doi":"10.1016/j.bonr.2025.101872","DOIUrl":"10.1016/j.bonr.2025.101872","url":null,"abstract":"<div><div>Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism caused by mutations in the <em>ALPL</em> gene, resulting in deficient activity of tissue-nonspecific alkaline phosphatase and impaired skeletal mineralization. Affected individuals have a higher prevalence of chronic kidney disease (CKD) than the general population. We report a woman who underwent craniosynostosis surgery in infancy and lost her deciduous teeth prematurely. From age 27, she experienced recurrent foot pain due to multiple metatarsal fractures. Low levels of total alkaline phosphatase (ALP) was noted at 39 years of age, and low activities for the three bone-specific ALP (BALP) isoforms B/I, B1 and B2. Genetic analysis revealed 2 missense variants in the <em>ALPL</em> gene (p.Glu191Lys and p.Gly456Arg) confirming HPP. At age 44, she developed bilateral hip fissures requiring right-sided total hip replacement. Treatment with the parathyroid hormone analogue teriparatide (20 μg/day) was initiated at age 50, leading to increased BALP isoform levels indicating improved mineralization, less bone pain, and no new fractures during 9 months of treatment, which was stopped due to hypercalcemia and hyperphosphatemia. She began peritoneal dialysis at age 55 and received a kidney transplant at age 58. At age 65, seven years post-transplantation, she remained free of new fractures and significant bone pain. This case illustrates the long-term natural history of HPP with progressive skeletal complications across decades, and highlights the potential of short-term teriparatide as a therapeutic option for symptom relief and improved mineralization. It also suggests that kidney transplantation may contribute to improved bone health in HPP with advanced CKD.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101872"},"PeriodicalIF":2.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prediction of biomechanical properties of ex vivo human femoral cortical bone using Raman spectroscopy and machine learning algorithms 利用拉曼光谱和机器学习算法预测离体人股骨皮质骨的生物力学特性

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-08-15 DOI: 10.1016/j.bonr.2025.101870

Mustafa UNAL , Ramazan UNLU , Sasidhar UPPUGANTI , Jeffry S. NYMAN

This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (n = 118 donors; age range 21–101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (K_init) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as ν₁Phosphate (PO₄)/CH₂-wag, ν₁PO₄/Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (K_init) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R²) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R² of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.

本研究将拉曼光谱（RS）应用于离体人尸体股骨骨干中段皮质骨标本（118例供体，年龄21-101岁），通过机器学习（ML）模型预测断裂韧性特性。光谱特征，连同人口统计学变量（年龄、性别）和结构参数（皮质孔隙度、体积骨矿物质密度），被输入到支持向量回归（SVR）、极端树回归（ETR）、极端梯度增强（XGB）和集合模型中，以预测断裂韧性指标，如裂纹起裂韧性（Kinit）和断裂能量（j积分）。特征选择基于拉曼衍生的矿物和有机基质参数，如ν1Phosphate (PO4)/CH2-wag， ν1PO4/Amide I等，以捕获骨的复杂组成。我们的研究结果表明，集成模型始终优于单个模型，使用集成方法预测裂纹起裂韧性（Kinit）的效果最好。其决定系数（R2）为0.623，均方根误差（RMSE）为1.320，平均绝对误差（MAE）为1.015，平均百分比绝对误差（MAPE）为0.134。对于裂纹扩展总能量（j积分）的预测，XGB模型的R2为0.737，RMSE为2.634，MAE为2.283，MAPE为0.240。该研究强调了结合矿物质量性质（MP）和有机基质性质（OMP）对提高预测精度的重要性。这项工作是首次将拉曼光谱与其他临床和结构特征结合起来预测人类皮质骨断裂韧性的研究，展示了人工智能（AI）和机器学习在推进骨骼研究方面的潜力。未来的研究可以集中在更大的数据集和更先进的建模技术上，以进一步提高预测能力。

{"title":"Prediction of biomechanical properties of ex vivo human femoral cortical bone using Raman spectroscopy and machine learning algorithms","authors":"Mustafa UNAL , Ramazan UNLU , Sasidhar UPPUGANTI , Jeffry S. NYMAN","doi":"10.1016/j.bonr.2025.101870","DOIUrl":"10.1016/j.bonr.2025.101870","url":null,"abstract":"<div><div>This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (<em>n</em> = 118 donors; age range 21–101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (K<sub>init</sub>) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as ν<sub>1</sub>Phosphate (PO<sub>4</sub>)/CH<sub>2</sub>-wag, ν<sub>1</sub>PO<sub>4</sub>/Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (K<sub>init</sub>) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R<sup>2</sup>) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R<sup>2</sup> of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101870"},"PeriodicalIF":2.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice 模拟微重力准确地模拟了长时间太空飞行对骨骼未成熟小鼠骨骼和骨骼肌的影响

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-08-15 DOI: 10.1016/j.bonr.2025.101871

Michael A. Friedman , Yasmina Zeineddine , Olivier Tuyambaze , Wesam Elhawabri , Ahmed Al Shammary , Louis Stodieck , Virginia L. Ferguson , Henry J. Donahue

Spaceflight (SF) and disuse result in decreases in bone and skeletal muscle volume that increase fracture risk. Hindlimb unloading (HLU) has been widely used to model the effects of microgravity. However, the effects of SF and HLU on bone and skeletal muscle have not been directly compared during long-duration SF. We examined the effects of five weeks of SF and HLU in the femurs of female Balb/c mice. For the first time, SF and HLU were directly compared using mice of the same age, strain, sex, and duration as a mission to the ISS. We hypothesized that HLU would accurately model SF, resulting in similar bone and skeletal muscle loss. Ten-week old female Balb/c mice were assigned to baseline, vivarium control, habitat control, and SF groups (n = 10/group). A separate cohort of 10-week female Balb/c mice were placed in HLU or control (n = 10/group). Femoral cortical area increased from baseline in all groups except HLU. The magnitudes of increases were lower in the SF and HLU groups. Similar effects were seen in trabecular bone. Femoral ultimate force decreased in SF and HLU groups, compared to control groups. Gastrocnemius and quadriceps mass was lower in SF and HLU mice than in control mice. HLU resulted in greater bone loss than SF, possibly due to differences in housing conditions. HLU effectively models long-duration effects of SF on the musculoskeletal system, highlighting its utility for studying astronaut health risks and developing countermeasures.

太空飞行（SF）和不使用导致骨骼和骨骼肌体积减少，增加骨折风险。后肢卸载（HLU）被广泛用于模拟微重力的影响。然而，SF和HLU对骨和骨骼肌的影响尚未在长时间SF中直接比较。我们检测了5周的SF和HLU对雌性Balb/c小鼠股骨的影响。第一次，SF和HLU直接比较使用相同的年龄，品系，性别和持续时间的小鼠作为国际空间站的任务。我们假设HLU可以准确地模拟SF，导致类似的骨骼和骨骼肌损失。将10周龄雌性Balb/c小鼠分为基线组、室内对照组、生境对照组和SF组（n = 10/组）。另取10周龄雌性Balb/c小鼠，分别置于HLU组和对照组（n = 10/组）。除HLU外，所有组的股骨皮质面积均较基线增加。SF组和HLU组的增加幅度较小。小梁骨也有类似的效果。与对照组相比，SF组和HLU组股骨极限力降低。SF和HLU小鼠腓肠肌和股四头肌质量低于对照组小鼠。HLU导致的骨质流失比SF更大，可能是由于住房条件的差异。HLU有效地模拟了SF对肌肉骨骼系统的长期影响，突出了其在研究宇航员健康风险和制定对策方面的实用性。

{"title":"Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice","authors":"Michael A. Friedman , Yasmina Zeineddine , Olivier Tuyambaze , Wesam Elhawabri , Ahmed Al Shammary , Louis Stodieck , Virginia L. Ferguson , Henry J. Donahue","doi":"10.1016/j.bonr.2025.101871","DOIUrl":"10.1016/j.bonr.2025.101871","url":null,"abstract":"<div><div>Spaceflight (SF) and disuse result in decreases in bone and skeletal muscle volume that increase fracture risk. Hindlimb unloading (HLU) has been widely used to model the effects of microgravity. However, the effects of SF and HLU on bone and skeletal muscle have not been directly compared during long-duration SF. We examined the effects of five weeks of SF and HLU in the femurs of female Balb/c mice. For the first time, SF and HLU were directly compared using mice of the same age, strain, sex, and duration as a mission to the ISS. We hypothesized that HLU would accurately model SF, resulting in similar bone and skeletal muscle loss. Ten-week old female Balb/c mice were assigned to baseline, vivarium control, habitat control, and SF groups (n = 10/group). A separate cohort of 10-week female Balb/c mice were placed in HLU or control (n = 10/group). Femoral cortical area increased from baseline in all groups except HLU. The magnitudes of increases were lower in the SF and HLU groups. Similar effects were seen in trabecular bone. Femoral ultimate force decreased in SF and HLU groups, compared to control groups. Gastrocnemius and quadriceps mass was lower in SF and HLU mice than in control mice. HLU resulted in greater bone loss than SF, possibly due to differences in housing conditions. HLU effectively models long-duration effects of SF on the musculoskeletal system, highlighting its utility for studying astronaut health risks and developing countermeasures.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101871"},"PeriodicalIF":2.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Partial cementocyte ablation does not reduce cellular cementum apposition in a mouse model of molar super-eruption 在小鼠磨牙超萌模型中，部分骨水泥细胞消融不能减少骨水泥细胞的附着

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-08-15 DOI: 10.1016/j.bonr.2025.101873

Fatma F. Mohamed , Aonjittra Phanrungsuwan , Francisco H. Nociti Jr. , Brian L. Foster

Cementocytes reside in the cellular cementum of the apical tooth root and resemble bone osteocytes in their markers, lacunocanalicular network, and response to mineralization defects. However, it is unclear if cementocytes have a role in regulating cellular cementum similar to that of osteocytes in controlling bone formation and resorption. The Dmp1Cre-iDTR^fl/fl (Dmp1-DTR) mouse sensitizes Dmp1-expressing cells, including osteocytes and cementocytes, to diphtheria toxin (DT), allowing selective ablation of cell populations. Compared to iDTR^fl/fl control (CTR) mice, 1.0 μg/kg intraperitoneal DT administration at 6 and 8 weeks of age increased femur cortical bone porosity and reduced alveolar bone density in Dmp1-DTR mice, validating the model. DT administration eliminated approximately 80 % of alveolar bone osteocytes and 60 % of cementocytes in Dmp1Cre-iDTR^fl/fl mice. Mice were subjected to the challenge of unopposed first molar super-eruption, which promotes increased cellular cementum apposition. Maxillary molars were bilaterally extracted at 7 weeks, and effects on cellular cementum accumulation in mandibular first molars were analyzed at 3 weeks post-procedure using micro-computed tomography and histology. DT-directed cementocyte ablation did not alter cellular cementum volume, density, or porosity vs. CTR mice. Immunostaining showed similar distributions between treatment groups of osteopontin (OPN), an extracellular matrix protein associated with axial tooth movement. Localization of DMP1 in cellular cementum and cementocyte networks of Dmp1-DTR mice appeared reduced compared to CTR mice. Within the limits of the study, these results suggest that cementocytes are not essential for new cellular cementum formation under challenge. Further insights into roles for cementocytes require additional in vivo approaches.

骨水泥细胞存在于尖牙根的细胞骨水泥中，在它们的标记物、腔隙管网络和对矿化缺陷的反应方面与骨细胞相似。然而，骨水泥细胞在调节骨水泥方面是否具有类似于骨细胞在控制骨形成和骨吸收方面的作用尚不清楚。Dmp1Cre-iDTRfl/fl （Dmp1-DTR）小鼠使表达dmp1的细胞（包括骨细胞和骨质细胞）对白喉毒素（DT）敏感，允许选择性消融细胞群。与iDTRfl/fl对照（CTR）小鼠相比，Dmp1-DTR小鼠在6和8周龄时腹腔注射1.0 μg/kg DT可增加股骨皮质骨孔隙度，降低牙槽骨密度，验证了模型的有效性。在Dmp1Cre-iDTRfl/fl小鼠中，DT治疗消除了大约80%的牙槽骨骨细胞和60%的骨水泥细胞。小鼠受到无对抗的第一磨牙超级爆发的挑战，这促进了细胞骨质增生。7周时双侧拔除上颌磨牙，术后3周通过显微计算机断层扫描和组织学分析对下颌第一磨牙骨质积累的影响。与CTR小鼠相比，ct定向骨水泥细胞消融没有改变骨水泥体积、密度或孔隙度。免疫染色显示骨桥蛋白（OPN）在治疗组之间的分布相似，骨桥蛋白是一种与轴向牙齿运动相关的细胞外基质蛋白。与CTR小鼠相比，DMP1 - dtr小鼠的细胞骨水泥和骨水泥细胞网络中的DMP1定位明显减少。在本研究的范围内，这些结果表明，在挑战下，骨水泥细胞并不是形成新细胞骨水泥所必需的。进一步了解胶质细胞的作用需要额外的体内方法。

{"title":"Partial cementocyte ablation does not reduce cellular cementum apposition in a mouse model of molar super-eruption","authors":"Fatma F. Mohamed , Aonjittra Phanrungsuwan , Francisco H. Nociti Jr. , Brian L. Foster","doi":"10.1016/j.bonr.2025.101873","DOIUrl":"10.1016/j.bonr.2025.101873","url":null,"abstract":"<div><div>Cementocytes reside in the cellular cementum of the apical tooth root and resemble bone osteocytes in their markers, lacunocanalicular network, and response to mineralization defects. However, it is unclear if cementocytes have a role in regulating cellular cementum similar to that of osteocytes in controlling bone formation and resorption. The Dmp1Cre-iDTR<sup>fl/fl</sup> (Dmp1-DTR) mouse sensitizes <em>Dmp1</em>-expressing cells, including osteocytes and cementocytes, to diphtheria toxin (DT), allowing selective ablation of cell populations. Compared to iDTR<sup>fl/fl</sup> control (CTR) mice, 1.0 μg/kg intraperitoneal DT administration at 6 and 8 weeks of age increased femur cortical bone porosity and reduced alveolar bone density in Dmp1-DTR mice, validating the model. DT administration eliminated approximately 80 % of alveolar bone osteocytes and 60 % of cementocytes in <em>Dmp1Cre</em>-iDTR<sup>fl/fl</sup> mice. Mice were subjected to the challenge of unopposed first molar super-eruption, which promotes increased cellular cementum apposition. Maxillary molars were bilaterally extracted at 7 weeks, and effects on cellular cementum accumulation in mandibular first molars were analyzed at 3 weeks post-procedure using micro-computed tomography and histology. DT-directed cementocyte ablation did not alter cellular cementum volume, density, or porosity vs. CTR mice. Immunostaining showed similar distributions between treatment groups of osteopontin (OPN), an extracellular matrix protein associated with axial tooth movement. Localization of DMP1 in cellular cementum and cementocyte networks of Dmp1-DTR mice appeared reduced compared to CTR mice. Within the limits of the study, these results suggest that cementocytes are not essential for new cellular cementum formation under challenge. Further insights into roles for cementocytes require additional in vivo approaches.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101873"},"PeriodicalIF":2.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inpatient rehabilitation fracture liaison service (FLS) improves outcomes for secondary prevention of hip fractures 住院康复骨折联络服务（FLS）改善髋部骨折二级预防的结果

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-08-08 DOI: 10.1016/j.bonr.2025.101869

Orit Mazza , Chemda Gluck , Noa Menkes-Caspi , Robyn Jacob Bornstein , Hagay Amir , Michael Bahar , Amir Haim

Background

Secondary fracture prevention is a well-defined treatment-gap within osteoporosis management. Fracture Liaison Service (FLS) coordinates the management and treatment of patients following a fragility fracture in order to close the care gap. We aim to assess the efficacy of the FLS initiative in the management and treatment of patients following fragility hip fracture in the inpatient rehabilitation setting.

Methods

This is a diagnostic, retrospective cohort study using a deidentified, electronic health record database. In the extraction process, patients with fragility hip fractures were identified. Patients after major trauma or malignancy were excluded. The prevalence of initiation and adherence to anti-osteoporotic treatments, including alendronate, risedronate, zoledronate, denosumab, romosozumab, and teriparatide, was compared between the rehabilitation FLS initiative patients and patients from other hospitals without FLS.

Results

A total of 4,124 patients with fragility hip fractures were identified between 2017 and 2021. The FLS initiative showed significantly higher rates of treatment initiation, with 72.1 % of patients receiving pharmacological therapy following a hip fracture, compared to 45.1 % in hospitals without FLS (p < 0.001). Patients in the FLS group also demonstrated higher rates of good adherence and lower rates of poor adherence (p < 0.001). Denosumab was the most commonly prescribed anti-osteoporotic treatment within the FLS initiative.

Conclusions

The FLS in the inpatient rehabilitation setting was found to be highly effective in improving time to treatment initiation and adherence rates to prescribe anti-osteoporosis therapy. These findings demonstrate the role of FLS in addressing the osteoporosis treatment gap following fragility hip fracture.

背景：在骨质疏松管理中，二级骨折预防是一个明确的治疗缺口。骨折联络服务（FLS）协调脆性骨折后患者的管理和治疗，以缩小护理差距。我们的目的是评估FLS在住院康复环境中管理和治疗脆性髋部骨折患者的疗效。方法：这是一项诊断性、回顾性队列研究，使用一个未识别的电子健康记录数据库。在拔牙过程中，识别出脆性髋部骨折患者。排除重大创伤或恶性肿瘤后的患者。比较了康复FLS患者和其他医院无FLS患者开始和坚持抗骨质疏松治疗的患病率，包括阿仑膦酸钠、利塞膦酸钠、唑来膦酸钠、地诺单抗、罗莫索单抗和特立帕肽。结果2017年至2021年共发现4124例脆性髋部骨折患者。FLS计划显示出更高的治疗起始率，72.1%的患者在髋部骨折后接受药物治疗，而没有FLS的医院为45.1% (p <；0.001)。FLS组患者也表现出较高的良好依从性和较低的不良依从性(p <；0.001)。在FLS计划中，Denosumab是最常用的抗骨质疏松治疗药物。结论在住院康复环境中使用FLS可有效提高患者的治疗起始时间和依从性。这些发现证明了FLS在解决脆性髋部骨折后骨质疏松症治疗缺口中的作用。

{"title":"Inpatient rehabilitation fracture liaison service (FLS) improves outcomes for secondary prevention of hip fractures","authors":"Orit Mazza , Chemda Gluck , Noa Menkes-Caspi , Robyn Jacob Bornstein , Hagay Amir , Michael Bahar , Amir Haim","doi":"10.1016/j.bonr.2025.101869","DOIUrl":"10.1016/j.bonr.2025.101869","url":null,"abstract":"<div><h3>Background</h3><div>Secondary fracture prevention is a well-defined treatment-gap within osteoporosis management. Fracture Liaison Service (FLS) coordinates the management and treatment of patients following a fragility fracture in order to close the care gap. We aim to assess the efficacy of the FLS initiative in the management and treatment of patients following fragility hip fracture in the inpatient rehabilitation setting.</div></div><div><h3>Methods</h3><div>This is a diagnostic, retrospective cohort study using a deidentified, electronic health record database. In the extraction process, patients with fragility hip fractures were identified. Patients after major trauma or malignancy were excluded. The prevalence of initiation and adherence to anti-osteoporotic treatments, including alendronate, risedronate, zoledronate, denosumab, romosozumab, and teriparatide, was compared between the rehabilitation FLS initiative patients and patients from other hospitals without FLS.</div></div><div><h3>Results</h3><div>A total of 4,124 patients with fragility hip fractures were identified between 2017 and 2021. The FLS initiative showed significantly higher rates of treatment initiation, with 72.1 % of patients receiving pharmacological therapy following a hip fracture, compared to 45.1 % in hospitals without FLS (p < 0.001). Patients in the FLS group also demonstrated higher rates of good adherence and lower rates of poor adherence (p < 0.001). Denosumab was the most commonly prescribed anti-osteoporotic treatment within the FLS initiative.</div></div><div><h3>Conclusions</h3><div>The FLS in the inpatient rehabilitation setting was found to be highly effective in improving time to treatment initiation and adherence rates to prescribe anti-osteoporosis therapy. These findings demonstrate the role of FLS in addressing the osteoporosis treatment gap following fragility hip fracture.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101869"},"PeriodicalIF":2.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-term tissue engineered periosteum-mediated allograft healing is hindered due to persistent fibrosis and limited allograft remodeling. 长期组织工程骨膜介导的同种异体移植物愈合受到持续纤维化和有限的同种异体移植物重塑的阻碍。

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-08-06 eCollection Date: 2025-09-01 DOI: 10.1016/j.bonr.2025.101865

Alyson March, Sandra H Castillo Aguirre, Roman Eliseev, Regine Choe, Danielle S W Benoit

Decellularized bone allografts are used in approximately 1/3 of grafting procedures and are preferred in treating critical-size bone defects, as volumetric constraints limit autografts. However, allografts demonstrate high failure rates, with 60 % of allografts failing within 10-years post-implantation. Allograft failure is linked to poor graft integration, which directly results from lack of periosteum, which surrounds bone and is necessary for successful bone healing. Therefore, a tissue-engineered periosteum (TEP) is a promising approach to recapitulate the missing periosteum and promote allograft healing. We have systematically developed an enzymatically degradable poly(ethylene glycol) (PEG) hydrogel with encapsulated mouse mesenchymal stem cells and osteoprogenitor cells, recapitulating key periosteal paracrine signals and producing improvements in bone allograft healing. While successful TEP-mediated allograft healing has been observed, previous studies have been limited to short-term healing (up to 16-weeks), which has yet to enable the observation of TEP-modified allograft healing resolution. To this end, this study extended evaluation of allograft healing in a murine femur defect model up to 12-months post-implantation. TEP-modified allografts demonstrated improvements in key bone healing outcomes, including graft vascularization and bone callus formation, at early time points (up to 9-weeks post-implantation), but improvements in healing outcomes compared to unmodified allografts were lost after 4-months post-implantation. In addition, unmodified allografts displayed incomplete healing up to 12-months post-implantation, with significant fibrotic tissue, incomplete graft remodeling, and inferior biomechanical strength observed. Given these results, future TEP designs should support long-term healing and graft remodeling to promote resolution of TEP-mediated graft healing in a clinically relevant timeline.

脱细胞异体骨移植在大约三分之一的移植手术中使用，并且首选用于治疗临界大小的骨缺陷，因为体积限制限制了自体移植。然而，同种异体移植的失败率很高，60%的同种异体移植在植入后10年内失败。同种异体移植失败与移植物整合不良有关，这直接导致缺乏骨膜，骨膜包围骨，是成功骨愈合所必需的。因此，组织工程骨膜（TEP）是一种很有前途的方法来重建缺失的骨膜并促进同种异体移植愈合。我们系统地开发了一种酶降解的聚乙二醇（PEG）水凝胶，包被小鼠间充质干细胞和骨祖细胞，再现了关键的骨膜旁分泌信号，并改善了同种异体骨移植愈合。虽然已经观察到tep介导的同种异体移植物愈合成功，但先前的研究仅限于短期愈合（长达16周），这还不能观察到tep修饰的同种异体移植物愈合的决议。为此，本研究将同种异体移植物在小鼠股骨缺损模型中的愈合评估延长至植入后12个月。tep修饰的同种异体移植物在早期时间点（植入后9周）显示出关键骨愈合结果的改善，包括移植物血管形成和骨痂形成，但与未修饰的同种异体移植物相比，在植入后4个月后愈合结果的改善消失了。此外，未修饰的同种异体移植物在植入后12个月显示不完全愈合，有明显的纤维化组织，移植物重塑不完全，并且观察到较差的生物力学强度。鉴于这些结果，未来的TEP设计应该支持长期愈合和移植物重塑，以促进TEP介导的移植物愈合在临床相关时间内的解决。

{"title":"Long-term tissue engineered periosteum-mediated allograft healing is hindered due to persistent fibrosis and limited allograft remodeling.","authors":"Alyson March, Sandra H Castillo Aguirre, Roman Eliseev, Regine Choe, Danielle S W Benoit","doi":"10.1016/j.bonr.2025.101865","DOIUrl":"10.1016/j.bonr.2025.101865","url":null,"abstract":"<p><p>Decellularized bone allografts are used in approximately 1/3 of grafting procedures and are preferred in treating critical-size bone defects, as volumetric constraints limit autografts. However, allografts demonstrate high failure rates, with 60 % of allografts failing within 10-years post-implantation. Allograft failure is linked to poor graft integration, which directly results from lack of periosteum, which surrounds bone and is necessary for successful bone healing. Therefore, a tissue-engineered periosteum (TEP) is a promising approach to recapitulate the missing periosteum and promote allograft healing. We have systematically developed an enzymatically degradable poly(ethylene glycol) (PEG) hydrogel with encapsulated mouse mesenchymal stem cells and osteoprogenitor cells, recapitulating key periosteal paracrine signals and producing improvements in bone allograft healing. While successful TEP-mediated allograft healing has been observed, previous studies have been limited to short-term healing (up to 16-weeks), which has yet to enable the observation of TEP-modified allograft healing resolution. To this end, this study extended evaluation of allograft healing in a murine femur defect model up to 12-months post-implantation. TEP-modified allografts demonstrated improvements in key bone healing outcomes, including graft vascularization and bone callus formation, at early time points (up to 9-weeks post-implantation), but improvements in healing outcomes compared to unmodified allografts were lost after 4-months post-implantation. In addition, unmodified allografts displayed incomplete healing up to 12-months post-implantation, with significant fibrotic tissue, incomplete graft remodeling, and inferior biomechanical strength observed. Given these results, future TEP designs should support long-term healing and graft remodeling to promote resolution of TEP-mediated graft healing in a clinically relevant timeline.</p>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"101865"},"PeriodicalIF":2.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of 650 nm laser acupuncture on cartilage, bone, and skeletal muscle in osteoarthritis 650nm激光针刺对骨关节炎软骨、骨和骨骼肌的影响

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-07-31 DOI: 10.1016/j.bonr.2025.101864

Seung-Ho Seo , Sang-Mi Kang , Yang-Hee You , Chang-Su Na

This study evaluated the therapeutic effects of 650 nm laser acupuncture at 10 mW and 20 mW in a monosodium iodoacetate (MIA) induced osteoarthritis (OA) rat model. OA was induced by intra-articular injection of MIA, and laser acupuncture was applied to GB34 and GB39 twice weekly for four weeks. Cartilage preservation was assessed by Safranin-O staining, pain by hind paw weight distribution, bone structure by micro-CT analysis of bone volume fraction, trabecular volume, and cortical thickness, and muscle condition by histology and wet weight of the gastrocnemius and quadriceps. Both laser treatments reduced cartilage degeneration and improved weight-bearing. The 10 mW group showed greater improvements than the 20 mW group, including higher proteoglycan content, better bone structural parameters, and greater muscle mass. These results indicate that 10 mW laser acupuncture is more effective than 20 mW in reducing joint damage and preserving musculoskeletal tissue. The findings support the use of low-power laser acupuncture as a non-invasive treatment for OA. The study also shows that higher laser power does not necessarily lead to better outcomes, highlighting the need for appropriate dose selection. Further studies are needed to assess long-term effects and investigate underlying mechanisms.

研究了10 mW和20 mW 650 nm激光针刺对碘乙酸钠（MIA）诱导的骨关节炎（OA）大鼠模型的治疗作用。采用MIA关节内注射诱导OA，激光针刺GB34、GB39，每周2次，连续4周。采用Safranin-O染色评估软骨保存情况，采用后爪重量分布评估疼痛情况，采用显微ct分析骨体积分数、骨小梁体积和骨皮质厚度评估骨结构，采用腓肠肌和股四头肌的组织学和湿重评估肌肉状况。两种激光治疗都能减少软骨变性并改善负重。与20 mW组相比，10 mW组表现出更大的改善，包括更高的蛋白聚糖含量、更好的骨结构参数和更大的肌肉质量。这些结果表明，10mw激光针刺在减轻关节损伤和保护肌肉骨骼组织方面比20mw更有效。研究结果支持使用低功率激光针灸作为OA的非侵入性治疗。该研究还表明，更高的激光功率不一定会带来更好的结果，强调了适当剂量选择的必要性。需要进一步的研究来评估长期影响和调查潜在的机制。

{"title":"Effects of 650 nm laser acupuncture on cartilage, bone, and skeletal muscle in osteoarthritis","authors":"Seung-Ho Seo , Sang-Mi Kang , Yang-Hee You , Chang-Su Na","doi":"10.1016/j.bonr.2025.101864","DOIUrl":"10.1016/j.bonr.2025.101864","url":null,"abstract":"<div><div>This study evaluated the therapeutic effects of 650 nm laser acupuncture at 10 mW and 20 mW in a monosodium iodoacetate (MIA) induced osteoarthritis (OA) rat model. OA was induced by intra-articular injection of MIA, and laser acupuncture was applied to GB34 and GB39 twice weekly for four weeks. Cartilage preservation was assessed by Safranin-O staining, pain by hind paw weight distribution, bone structure by micro-CT analysis of bone volume fraction, trabecular volume, and cortical thickness, and muscle condition by histology and wet weight of the gastrocnemius and quadriceps. Both laser treatments reduced cartilage degeneration and improved weight-bearing. The 10 mW group showed greater improvements than the 20 mW group, including higher proteoglycan content, better bone structural parameters, and greater muscle mass. These results indicate that 10 mW laser acupuncture is more effective than 20 mW in reducing joint damage and preserving musculoskeletal tissue. The findings support the use of low-power laser acupuncture as a non-invasive treatment for OA. The study also shows that higher laser power does not necessarily lead to better outcomes, highlighting the need for appropriate dose selection. Further studies are needed to assess long-term effects and investigate underlying mechanisms.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101864"},"PeriodicalIF":2.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144770959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of fatty acid analogues with potent anabolic effects on bone in male mice 对雄性小鼠骨具有强合成代谢作用的脂肪酸类似物的研制

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-07-30 DOI: 10.1016/j.bonr.2025.101862

Jian-ming Lin , Ivo Dimitrov , Karen E. Callon , Maureen Watson , Ian R. Reid , William A. Denny , Jillian Cornish

Natural fatty acids are inhibitory to osteoclastogenesis, but only mildly so, as reported earlier by our and other groups. To improve the potency, we have synthesized two categories of analogues based on the backbone of saturated palmitic acid by inserting an ether or a triazole group in the carbon chain. The most effective compound proved to be with a triazole moiety farthest away from the acid unit. Following this strategy, we now have developed even more potent molecules, methylated triazole and tetrazole analogues. Tetrazole analogue displays about 10-fold higher inhibitory activity over the natural counterpart as tested in the osteoclastogenesis assay using mouse bone marrow cell cultures. Importantly, this inhibition is not due to cytotoxicity as both the methylated triazole and tetrazole molecules slightly increase the viability of bone marrow cells. It was found that the inhibition of osteoclastogenesis by the tetrazole analogue in mouse bone marrow cultures is associated with the decreased expression of the key osteoclastogenic or osteoclastic marker genes: Dcstamp, Nfatc1, Tnfa, Trap and Ctsk. The best analogue-tetrazole was then tested in vivo in a mouse calvarial local injection model after being solubilized by (2-hydroxypropyl)-β-cyclodextrin (β-CD). The results show that the tetrazole at the daily dose of 40 μg/injection (along with 264 μg β-CD) significantly reduce TRAP surface, and significantly increased mineralizing surface/bone surface, mineral apposition rate and bone formation rate. This study provides a novel effective agent for inhibiting osteoclastogenesis and positively regulating bone homeostasis.

天然脂肪酸对破骨细胞的形成有抑制作用，但只有轻微的抑制作用，正如我们和其他研究小组先前所报道的那样。为了提高效力，我们在饱和棕榈酸的骨架上，通过在碳链上插入醚或三唑，合成了两类类似物。最有效的化合物被证明是离酸单元最远的三唑部分。根据这一策略，我们现在已经开发出更有效的分子，甲基化三唑和四唑类似物。在小鼠骨髓细胞培养的破骨细胞生成实验中，四氮唑类似物显示出比天然对应物高10倍的抑制活性。重要的是，这种抑制不是由于细胞毒性，因为甲基化的三唑和四唑分子都会略微增加骨髓细胞的活力。在小鼠骨髓培养中发现，四唑类似物对破骨细胞生成的抑制作用与关键破骨细胞或破骨细胞标记基因Dcstamp、Nfatc1、Tnfa、Trap和Ctsk的表达降低有关。然后用（2-羟丙基）-β-环糊精（β-CD）溶解后，在小鼠颅骨局部注射模型中进行体内实验。结果表明，日剂量为40 μg/次的四唑（与264 μg β-CD一起）显著降低了TRAP表面，显著提高了矿化面/骨表面、矿物附着率和骨形成率。本研究为抑制破骨细胞生成和积极调节骨稳态提供了一种新的有效药物。

{"title":"Development of fatty acid analogues with potent anabolic effects on bone in male mice","authors":"Jian-ming Lin , Ivo Dimitrov , Karen E. Callon , Maureen Watson , Ian R. Reid , William A. Denny , Jillian Cornish","doi":"10.1016/j.bonr.2025.101862","DOIUrl":"10.1016/j.bonr.2025.101862","url":null,"abstract":"<div><div>Natural fatty acids are inhibitory to osteoclastogenesis, but only mildly so, as reported earlier by our and other groups. To improve the potency, we have synthesized two categories of analogues based on the backbone of saturated palmitic acid by inserting an ether or a triazole group in the carbon chain. The most effective compound proved to be with a triazole moiety farthest away from the acid unit. Following this strategy, we now have developed even more potent molecules, methylated triazole and tetrazole analogues. Tetrazole analogue displays about 10-fold higher inhibitory activity over the natural counterpart as tested in the osteoclastogenesis assay using mouse bone marrow cell cultures. Importantly, this inhibition is not due to cytotoxicity as both the methylated triazole and tetrazole molecules slightly increase the viability of bone marrow cells. It was found that the inhibition of osteoclastogenesis by the tetrazole analogue in mouse bone marrow cultures is associated with the decreased expression of the key osteoclastogenic or osteoclastic marker genes: <em>Dcstamp</em>, <em>Nfatc1</em>, <em>Tnfa</em>, <em>Trap</em> and <em>Ctsk</em>. The best analogue-tetrazole was then tested <em>in vivo</em> in a mouse calvarial local injection model after being solubilized by (2-hydroxypropyl)-β-cyclodextrin (β-CD). The results show that the tetrazole at the daily dose of 40 μg/injection (along with 264 μg β-CD) significantly reduce TRAP surface, and significantly increased mineralizing surface/bone surface, mineral apposition rate and bone formation rate. This study provides a novel effective agent for inhibiting osteoclastogenesis and positively regulating bone homeostasis.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101862"},"PeriodicalIF":2.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteoblasts sense extracellular levels of phosphate to control the local expression of phosphatases for matrix mineralisation 成骨细胞通过感知细胞外的磷酸盐水平来控制磷酸酶在基质矿化中的局部表达

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-07-30 DOI: 10.1016/j.bonr.2025.101863

Soher Nagi Jayash, Thomas Duff, Qaisar Tanveer, Worachet Promruk, Colin Farquharson

The provision of inorganic phosphate (P_i) for biomineralisation is under systemic and local control. Locally, osteoblast production of phosphatases such as tissue-nonspecific alkaline phosphatase (TNAP) and PHOSPHO1 is required for normal skeletal mineralisation and osteoblasts may sense extracellular P_i concentrations to control local phosphatase activity and thereby “fine-tune” P_i production and delivery for biomineralisation. This has been poorly explored and this study examined the ability of osteoblasts to sense and respond to extracellular P_i to control the local expression of TNAP and PHOSPHO1.

Extracellular P_i downregulated the expression of PHOSPHO1 and TNAP by human primary osteoblasts at both mRNA and protein levels. Increasing P_i concentrations also reduced the mRNA expression of the type III Na- P_i co-transporters, PiT-1 and PiT-2 and selectively enhanced ERK1/2 phosphorylation. Inhibition of PiT-1 and PiT-2 by Foscarnet or MEK1/2 by UO126 abolished the downregulation of PHOSPHO1 and ALPL expression by extracellular Pi. Moreover, extracellular P_i phosphorylated fibroblast growth factor receptor (FGFR) substrate 2α (FRS2α) and this activation was abolished by Foscarnet. Also, blocking FGFR signalling inhibited the phosphorylation of ERK1/2 and prevented the decrease in ALPL and PHOSPHO1 expression by extracellular P_i. Similar results were observed in cultured murine calvaria. Osteoblast matrix mineralisation by extracellular P_i was dependent upon type III Na- P_i co-transporters and FGFR signalling.

In conclusion, these results suggest an interplay between FGFR and P_i transporters is required for osteoblasts to sense and respond to extracellular P_i. This understanding advances our knowledge of the molecular control of physiological bone mineralisation by osteoblasts.

无机磷酸盐（Pi）的生物矿化是在系统和局部控制下提供的。局部，成骨细胞产生的磷酸酶，如组织非特异性碱性磷酸酶（TNAP）和PHOSPHO1，是正常骨骼矿化所必需的，成骨细胞可以感知细胞外Pi浓度来控制局部磷酸酶活性，从而“微调”Pi的产生和传递，以实现生物矿化。这方面的研究很少，本研究检测了成骨细胞感知和响应细胞外Pi的能力，以控制TNAP和PHOSPHO1的局部表达。胞外Pi在mRNA和蛋白水平上下调人原代成骨细胞PHOSPHO1和TNAP的表达。增加Pi浓度也降低了III型Na- Pi共转运体pit1和pit2的mRNA表达，并选择性地增强了ERK1/2的磷酸化。UO126对Foscarnet或MEK1/2对PiT-1和PiT-2的抑制消除了细胞外Pi对PHOSPHO1和ALPL表达的下调。此外，胞外Pi磷酸化成纤维细胞生长因子受体（FGFR）底物2α (FRS2α)，这种激活被Foscarnet消除。此外，阻断FGFR信号传导可抑制ERK1/2的磷酸化，阻止细胞外Pi对ALPL和PHOSPHO1表达的降低。在培养的小鼠颅骨中也观察到类似的结果。细胞外Pi的成骨细胞基质矿化依赖于III型Na- Pi共转运蛋白和FGFR信号传导。总之，这些结果表明，FGFR和Pi转运蛋白之间的相互作用是成骨细胞感知和响应细胞外Pi的必要条件。这种理解促进了我们对成骨细胞生理骨矿化的分子控制的认识。

{"title":"Osteoblasts sense extracellular levels of phosphate to control the local expression of phosphatases for matrix mineralisation","authors":"Soher Nagi Jayash, Thomas Duff, Qaisar Tanveer, Worachet Promruk, Colin Farquharson","doi":"10.1016/j.bonr.2025.101863","DOIUrl":"10.1016/j.bonr.2025.101863","url":null,"abstract":"<div><div>The provision of inorganic phosphate (P<sub>i</sub>) for biomineralisation is under systemic and local control. Locally, osteoblast production of phosphatases such as tissue-nonspecific alkaline phosphatase (TNAP) and PHOSPHO1 is required for normal skeletal mineralisation and osteoblasts may sense extracellular P<sub>i</sub> concentrations to control local phosphatase activity and thereby “fine-tune” P<sub>i</sub> production and delivery for biomineralisation. This has been poorly explored and this study examined the ability of osteoblasts to sense and respond to extracellular P<sub>i</sub> to control the local expression of TNAP and PHOSPHO1.</div><div>Extracellular P<sub>i</sub> downregulated the expression of PHOSPHO1 and TNAP by human primary osteoblasts at both mRNA and protein levels. Increasing P<sub>i</sub> concentrations also reduced the mRNA expression of the type III Na- P<sub>i</sub> co-transporters, PiT-1 and PiT-2 and selectively enhanced ERK1/2 phosphorylation. Inhibition of PiT-1 and PiT-2 by Foscarnet or MEK1/2 by UO126 abolished the downregulation of <em>PHOSPHO1</em> and <em>ALPL</em> expression by extracellular Pi. Moreover, extracellular P<sub>i</sub> phosphorylated fibroblast growth factor receptor (FGFR) substrate 2α (FRS2α) and this activation was abolished by Foscarnet. Also, blocking FGFR signalling inhibited the phosphorylation of ERK1/2 and prevented the decrease in <em>ALPL</em> and <em>PHOSPHO1</em> expression by extracellular P<sub>i</sub>. Similar results were observed in cultured murine calvaria. Osteoblast matrix mineralisation by extracellular P<sub>i</sub> was dependent upon type III Na- P<sub>i</sub> co-transporters and FGFR signalling.</div><div>In conclusion, these results suggest an interplay between FGFR and P<sub>i</sub> transporters is required for osteoblasts to sense and respond to extracellular P<sub>i</sub>. This understanding advances our knowledge of the molecular control of physiological bone mineralisation by osteoblasts.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101863"},"PeriodicalIF":2.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Experimental analysis of bone marrow adipose tissue and bone marrow adipocytes: An update from the bone marrow adiposity society (BMAS) 骨髓脂肪组织和骨髓脂肪细胞的实验分析：来自骨髓脂肪学会（BMAS）的最新进展

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-07-28 DOI: 10.1016/j.bonr.2025.101861

Michaela Tencerova , Biagio Palmisano , Stéphanie Lucas , Camille Attané , Kaisa K. Ivaska , Léa Loisay , Yoshiko M. Ikushima , Drenka Trivanovic , Alessandro Corsi , Adriana Roque , Hongshuai Li , Friederike Behler-Janbeck , Jeroen Geurts , Mara Riminucci , Izabela Podgorski , William P. Cawthorn , Bram C.J. van der Eerden , André J. van Wijnen

Bone marrow adipose tissue (BMAT) is physiologically linked to bone and energy metabolism, endocrine regulation, hematopoiesis and cancer-related processes. A key challenge in the field is that methods for isolating BMAT or bone marrow adipocytes (BMAds) are variable because there are no widely adopted standardized protocols. To generate awareness of this challenge and to establish uniformity in experimental approaches requiring isolation, storage and characterization of BMAT and BMAds, the Biobanking Working Group of the international Bone Marrow Adiposity Society (BMAS) has previously recommended experimental standards. This paper provides an update on this effort and presents current state-of-the-art methods and technical considerations for isolation and characterization of BMAT and BMAds, including currently available high-throughput omics approaches. This review provides a reference point based on the consensus view of BMAS investigators to support studies on biomedical, biological, biochemical and biophysical questions associated with bone marrow adiposity.

骨髓脂肪组织（BMAT）在生理上与骨和能量代谢、内分泌调节、造血和癌症相关过程有关。该领域的一个关键挑战是分离BMAT或骨髓脂肪细胞（BMAds）的方法是可变的，因为没有广泛采用的标准化方案。为了提高对这一挑战的认识，并在需要分离、储存和表征BMAT和BMAds的实验方法上建立一致性，国际骨髓肥胖协会（BMAS）的生物银行工作组先前推荐了实验标准。本文提供了这项工作的最新进展，并介绍了目前最先进的分离和表征BMAT和BMAds的方法和技术考虑，包括目前可用的高通量组学方法。这篇综述提供了一个参考点，基于BMAS研究者的共识，以支持与骨髓肥胖相关的生物医学、生物学、生化和生物物理问题的研究。

{"title":"Experimental analysis of bone marrow adipose tissue and bone marrow adipocytes: An update from the bone marrow adiposity society (BMAS)","authors":"Michaela Tencerova , Biagio Palmisano , Stéphanie Lucas , Camille Attané , Kaisa K. Ivaska , Léa Loisay , Yoshiko M. Ikushima , Drenka Trivanovic , Alessandro Corsi , Adriana Roque , Hongshuai Li , Friederike Behler-Janbeck , Jeroen Geurts , Mara Riminucci , Izabela Podgorski , William P. Cawthorn , Bram C.J. van der Eerden , André J. van Wijnen","doi":"10.1016/j.bonr.2025.101861","DOIUrl":"10.1016/j.bonr.2025.101861","url":null,"abstract":"<div><div>Bone marrow adipose tissue (BMAT) is physiologically linked to bone and energy metabolism, endocrine regulation, hematopoiesis and cancer-related processes. A key challenge in the field is that methods for isolating BMAT or bone marrow adipocytes (BMAds) are variable because there are no widely adopted standardized protocols. To generate awareness of this challenge and to establish uniformity in experimental approaches requiring isolation, storage and characterization of BMAT and BMAds, the Biobanking Working Group of the international Bone Marrow Adiposity Society (BMAS) has previously recommended experimental standards. This paper provides an update on this effort and presents current state-of-the-art methods and technical considerations for isolation and characterization of BMAT and BMAds, including currently available high-throughput omics approaches. This review provides a reference point based on the consensus view of BMAS investigators to support studies on biomedical, biological, biochemical and biophysical questions associated with bone marrow adiposity.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101861"},"PeriodicalIF":2.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0