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Advancing HR-pQCT-based homogenised FE models with smooth structured hexahedral meshes
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-23 DOI: 10.1016/j.bone.2025.117394
Simone Poncioni , Kurt Lippuner , Philippe Zysset
Nonlinear homogenised finite element (hFE) models can accurately predict stiffness and strength of ultra-distal sections of the radius and tibia using in vivo HR-pQCT images. Recent findings showed good stiffness prediction at these distal sections but a limited ability to reproduce experimental strain localisation. The coarseness of voxel-based meshes reduces the computational effort at the cost of heavily simplifying the underlying geometry of the cortex, the gradient of material properties, and the resulting strain distribution. To overcome these limitations, we present a comprehensive approach to generating fully automated, smooth, and structured hexahedral meshes for HR-pQCT scans at the distal radius and tibia. This study used three datasets to validate the proposed hFE pipeline and its short-term repeatability: ex vivo 2nd generation HR-pQCT images of 21 human radii and 25 human tibiae, and 208 in vivo images from same-day repeated scans on 39 individuals. Results show high accuracy in predicting stiffness (tibia: R2=0.94, radius: R2=0.88) and yield force (tibia: R2=0.93, radius: R2=0.95). Mesh sensitivity analysis reveals stabilisation within a ± 3 % error margin. Dice similarity coefficients between mesh and scanned image were >0.98, and good element quality was achieved across the validation datasets (tibia: SICNavg=0.809, radius: SICNavg=0.764). Along with the improved volumetric representation of distal cortical and trabecular bone geometry and the good element quality, the new pipeline shows gains in computational performance: 11.70±1.49 min for triple-stack tibia images and 11.00±0.97 min for double-stack radius images, respectively. Generating structured meshes with consistent element-to-element correspondence facilitates seamless comparison between patient models or in longitudinal settings, providing an additional clinical information.
{"title":"Advancing HR-pQCT-based homogenised FE models with smooth structured hexahedral meshes","authors":"Simone Poncioni ,&nbsp;Kurt Lippuner ,&nbsp;Philippe Zysset","doi":"10.1016/j.bone.2025.117394","DOIUrl":"10.1016/j.bone.2025.117394","url":null,"abstract":"<div><div>Nonlinear homogenised finite element (hFE) models can accurately predict stiffness and strength of ultra-distal sections of the radius and tibia using <em>in vivo</em> HR-pQCT images. Recent findings showed good stiffness prediction at these distal sections but a limited ability to reproduce experimental strain localisation. The coarseness of voxel-based meshes reduces the computational effort at the cost of heavily simplifying the underlying geometry of the cortex, the gradient of material properties, and the resulting strain distribution. To overcome these limitations, we present a comprehensive approach to generating fully automated, smooth, and structured hexahedral meshes for HR-pQCT scans at the distal radius and tibia. This study used three datasets to validate the proposed hFE pipeline and its short-term repeatability: <em>ex vivo</em> 2nd generation HR-pQCT images of 21 human radii and 25 human tibiae, and 208 <em>in vivo</em> images from same-day repeated scans on 39 individuals. Results show high accuracy in predicting stiffness (tibia: <span><math><msup><mi>R</mi><mn>2</mn></msup><mo>=</mo><mn>0.94</mn></math></span>, radius: <span><math><msup><mi>R</mi><mn>2</mn></msup><mo>=</mo><mn>0.88</mn><mo>)</mo></math></span> and yield force (tibia: <span><math><msup><mi>R</mi><mn>2</mn></msup><mo>=</mo><mn>0.93</mn><mo>,</mo></math></span> radius: <span><math><msup><mi>R</mi><mn>2</mn></msup><mo>=</mo><mn>0.95</mn><mo>)</mo><mo>.</mo></math></span> Mesh sensitivity analysis reveals stabilisation within a <span><math><mo>±</mo></math></span> 3 % error margin. Dice similarity coefficients between mesh and scanned image were <span><math><mo>&gt;</mo><mn>0.98</mn><mo>,</mo></math></span> and good element quality was achieved across the validation datasets (tibia: <span><math><mfenced><mrow><mi>S</mi><mo>−</mo></mrow></mfenced><msub><mi>ICN</mi><mi>avg</mi></msub><mo>=</mo><mn>0.809</mn><mo>,</mo></math></span> radius: <span><math><mfenced><mrow><mi>S</mi><mo>−</mo></mrow></mfenced><msub><mi>ICN</mi><mi>avg</mi></msub><mo>=</mo><mn>0.764</mn><mo>)</mo><mo>.</mo></math></span> Along with the improved volumetric representation of distal cortical and trabecular bone geometry and the good element quality, the new pipeline shows gains in computational performance: <span><math><mfenced><mrow><mn>11.70</mn><mo>±</mo><mn>1.49</mn></mrow></mfenced></math></span> min for triple-stack tibia images and <span><math><mfenced><mrow><mn>11.00</mn><mo>±</mo><mn>0.97</mn></mrow></mfenced></math></span> min for double-stack radius images, respectively. Generating structured meshes with consistent element-to-element correspondence facilitates seamless comparison between patient models or in longitudinal settings, providing an additional clinical information.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117394"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Associations of the serum 25-hydroxyvitamin D with mortality among patients in osteopenia or osteoporosis
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-23 DOI: 10.1016/j.bone.2025.117408
Ming Ma , Yuji Zhang , Jinmin Liu , Cong Tian , Zhenkun Duan , Xingchun Huang , Bin Geng

Purpose

The correlation between serum 25-hydroxy vitamin D [(25(OH)D] and mortality in patients with osteopenia or osteoporosis remains unclear. Therefore, this study examined the relationship between serum 25(OH)D and mortality in patients with osteopenia or osteoporosis.

Methods and results

This prospective cohort study included patients with osteopenia or osteoporosis from the National Health and Nutrition Examination Survey from 2001 to 2018. Multivariate Cox regression models examined the correlation between serum 25(OH)D and all-cause mortality, cardiovascular mortality (CVD), and cancer mortality. The cohort included 9282 adult participants with a median follow-up period of 97.01 months, including 1394 all-cause deaths, 413 CVD-related deaths, and 322 cancer deaths. In fully adjusted models, higher serum 25(OH)D levels (≥75.0 nmol/L) were associated with a lower risk of all-cause mortality (hazard ratio 0.54, 95 % confidence interval 0.41 to 0.73) and cardiovascular death (0.47, 0.29 to 0.76), using participants with low 25(OH)D levels (<25 nmol/L) as the reference. In addition, we found an L-shaped non-linear dose-response relationship between serum 25(OH)D and all-cause and cardiovascular mortality, with inflection points of 38.8 nmol/L and 53.6 nmol/L, respectively.

Conclusion

Higher serum 25(OH)D concentrations are strongly associated with a diminished risk of all-cause and CVD mortality in patients with osteopenia or osteoporosis. This association has a threshold effect. More in-depth intervention studies are needed to clarify underlying mechanisms.
{"title":"Associations of the serum 25-hydroxyvitamin D with mortality among patients in osteopenia or osteoporosis","authors":"Ming Ma ,&nbsp;Yuji Zhang ,&nbsp;Jinmin Liu ,&nbsp;Cong Tian ,&nbsp;Zhenkun Duan ,&nbsp;Xingchun Huang ,&nbsp;Bin Geng","doi":"10.1016/j.bone.2025.117408","DOIUrl":"10.1016/j.bone.2025.117408","url":null,"abstract":"<div><h3>Purpose</h3><div>The correlation between serum 25-hydroxy vitamin D [(25(OH)D] and mortality in patients with osteopenia or osteoporosis remains unclear. Therefore, this study examined the relationship between serum 25(OH)D and mortality in patients with osteopenia or osteoporosis.</div></div><div><h3>Methods and results</h3><div>This prospective cohort study included patients with osteopenia or osteoporosis from the National Health and Nutrition Examination Survey from 2001 to 2018. Multivariate Cox regression models examined the correlation between serum 25(OH)D and all-cause mortality, cardiovascular mortality (CVD), and cancer mortality. The cohort included 9282 adult participants with a median follow-up period of 97.01 months, including 1394 all-cause deaths, 413 CVD-related deaths, and 322 cancer deaths. In fully adjusted models, higher serum 25(OH)D levels (≥75.0 nmol/L) were associated with a lower risk of all-cause mortality (hazard ratio 0.54, 95 % confidence interval 0.41 to 0.73) and cardiovascular death (0.47, 0.29 to 0.76), using participants with low 25(OH)D levels (&lt;25 nmol/L) as the reference. In addition, we found an L-shaped non-linear dose-response relationship between serum 25(OH)D and all-cause and cardiovascular mortality, with inflection points of 38.8 nmol/L and 53.6 nmol/L, respectively.</div></div><div><h3>Conclusion</h3><div>Higher serum 25(OH)D concentrations are strongly associated with a diminished risk of all-cause and CVD mortality in patients with osteopenia or osteoporosis. This association has a threshold effect. More in-depth intervention studies are needed to clarify underlying mechanisms.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117408"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Parathyroid hormone levels following denosumab vs. zoledronic acid therapy for osteoporosis
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-23 DOI: 10.1016/j.bone.2025.117407
Pnina Rotman-Pikielny , Liat Barzilai-Yosef , Erez Ramaty , Sofia Braginski-Shapira , Michal Kasher Meron , Tzipi Hornik Lurie
The objective of this retrospective, database study was to characterize the rate, magnitude and timeline of increases in parathyroid hormone (PTH) levels post-denosumab (DMAb) vs. zoledronic acid (ZA) injection in patients with osteoporosis and near normal baseline PTH. Included were osteoporotic females, 50 years, initiating treatment with 60 mg DMAb or 5 mg ZA. PTH levels within 6-months post-DMAb or 12-months post-ZA injection were extracted from the electronic database of a 4.5 million-member health maintenance organization. The indication for PTH measurements was unknown. Exclusion criteria were creatinine >2 mg/dL, vitamin D < 50 nmol/L or parathyroid hormone level > 1.5 × upper limit of normal (ULN). Among 3317 women, 1992 received DMAb and 1325 ZA. The DMAb group was older (73.3 ± 8.5 vs. 69.8 ± 8.6 years, p < 0.001) and more patients treated with DMAb compared with patients treated with ZA had prior non-vertebral fractures (7.7 % vs. 5.2 %, p < 0.01) and had previously been treated with osteoporosis medication (56.3 % vs. 50.3 %, p < 0.001). Among the patients, 14.9 % had at least one post-treatment PTH > 1.5 ULN. Of 7273 post-treatment PTH tests, 62.6 % were within normal limits, while 24.8 % were mildly elevated at 1.01–1.5 ULN. Two-months after both treatments, >1.5 ULN PTH levels peaked at ∼20 %. Elevated PTH was associated with eGFR < 60 mL/min/1.73 m2 and comorbidities. In conclusion, most PTH levels post-DMAb or ZA in osteoporotic patients with baseline PTH < 1.5 ULN, were within normal range. PTH increased to >1.5 ULN in 14.9 % of patients; peaking in the first 2-months post-treatment and declining thereafter. Elevated PTH may be related to anti-resorptive effects and is not medication specific. PTH measurements in the first few months post-DMAb and ZA therapy should be limited.
{"title":"Parathyroid hormone levels following denosumab vs. zoledronic acid therapy for osteoporosis","authors":"Pnina Rotman-Pikielny ,&nbsp;Liat Barzilai-Yosef ,&nbsp;Erez Ramaty ,&nbsp;Sofia Braginski-Shapira ,&nbsp;Michal Kasher Meron ,&nbsp;Tzipi Hornik Lurie","doi":"10.1016/j.bone.2025.117407","DOIUrl":"10.1016/j.bone.2025.117407","url":null,"abstract":"<div><div>The objective of this retrospective, database study was to characterize the rate, magnitude and timeline of increases in parathyroid hormone (PTH) levels post-denosumab (DMAb) vs. zoledronic acid (ZA) injection in patients with osteoporosis and near normal baseline PTH. Included were osteoporotic females, <span><math><mo>≥</mo></math></span>50 years, initiating treatment with 60 mg DMAb or 5 mg ZA. PTH levels within 6-months post-DMAb or 12-months post-ZA injection were extracted from the electronic database of a 4.5 million-member health maintenance organization. The indication for PTH measurements was unknown. Exclusion criteria were creatinine &gt;2 mg/dL, vitamin D &lt; 50 nmol/L or parathyroid hormone level &gt; 1.5 × upper limit of normal (ULN). Among 3317 women, 1992 received DMAb and 1325 ZA. The DMAb group was older (73.3 ± 8.5 vs. 69.8 ± 8.6 years, <em>p</em> &lt; 0.001) and more patients treated with DMAb compared with patients treated with ZA had prior non-vertebral fractures (7.7 % vs. 5.2 %, <em>p</em> &lt; 0.01) and had previously been treated with osteoporosis medication (56.3 % vs. 50.3 %, <em>p</em> &lt; 0.001). Among the patients, 14.9 % had at least one post-treatment PTH &gt; 1.5 ULN. Of 7273 post-treatment PTH tests, 62.6 % were within normal limits, while 24.8 % were mildly elevated at 1.01–1.5 ULN. Two-months after both treatments, &gt;1.5 ULN PTH levels peaked at ∼20 %. Elevated PTH was associated with eGFR &lt; 60 mL/min/1.73 m<sup>2</sup> and comorbidities. In conclusion, most PTH levels post-DMAb or ZA in osteoporotic patients with baseline PTH &lt; 1.5 ULN, were within normal range. PTH increased to &gt;1.5 ULN in 14.9 % of patients; peaking in the first 2-months post-treatment and declining thereafter. Elevated PTH may be related to anti-resorptive effects and is not medication specific. PTH measurements in the first few months post-DMAb and ZA therapy should be limited.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117407"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Automatic segmentation of cortical bone microstructure: Application and analysis of three proximal femur sites
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-23 DOI: 10.1016/j.bone.2025.117404
Mathieu Simon , Silvia Owusu , Stefan Bracher , Dieter D. Bosshardt , Michael Pretterklieber , Philippe Zysset
Osteoporosis is the most common bone metabolic unbalance, leading to fragility fractures, which are known to be associated with structural changes in the bone. Cortical bone accounts for 80 % of the skeleton mass and undergoes remodeling throughout life, leading to changes in its thickness and microstructure. Although many studies quantified the different cortical bone structures using CT techniques (3D), they are often realised on a small number of samples. Therefore, the work presented here proposes a method to quantify cortical bone microstructure using 2D histology, shows its application on a set of 94 samples and compares to 3D methods.
Fresh frozen human femur pairs from 47 donors aged between 57 and 96 years were obtained from the Medical University of Vienna. Bone samples were cut from 3 sites: proximal part of the diaphysis, inferior and superior segments of the neck. The samples were stained with toluidine blue and imaged under light microscopy. After manual segmentation of a few regions of interest by multiple operators, a convolutional neural network was trained in combination with a random forest for automatic segmentation. The segmentation analysis compares morphology and structure distribution of Haversian canals, osteocyte lacunae, and cement lines with literature, between anatomical sites, sex, left and right sides, and relation to ageing.
Morphological analysis of the segmentation gives results similar to the literature. Comparison between male and female donors shows no significant differences. There is no significant difference between left and right femur on paired samples but significant differences are observed between anatomical locations. The structures' relative amounts do not present significant changes with age but only weak tendencies. Nevertheless, a strong correlation was observed between osteocyte lacunae density and bone areal fraction.
This study presents a full process to stain and automatically segment digital cortical bone images. Its application to a large sample set of proximal femora provides strong statistics on the cortical bone structures morphology and distribution. Similarities observed between sides and sexes together with differences observed between sites could indicate that mechanical loading might be a main driver for bone microstructure. Additionally, the relationship between osteocyte lacunae density and bone areal fraction could suggest that bone porosity is regulated by osteocyte survival.
{"title":"Automatic segmentation of cortical bone microstructure: Application and analysis of three proximal femur sites","authors":"Mathieu Simon ,&nbsp;Silvia Owusu ,&nbsp;Stefan Bracher ,&nbsp;Dieter D. Bosshardt ,&nbsp;Michael Pretterklieber ,&nbsp;Philippe Zysset","doi":"10.1016/j.bone.2025.117404","DOIUrl":"10.1016/j.bone.2025.117404","url":null,"abstract":"<div><div>Osteoporosis is the most common bone metabolic unbalance, leading to fragility fractures, which are known to be associated with structural changes in the bone. Cortical bone accounts for 80 % of the skeleton mass and undergoes remodeling throughout life, leading to changes in its thickness and microstructure. Although many studies quantified the different cortical bone structures using CT techniques (3D), they are often realised on a small number of samples. Therefore, the work presented here proposes a method to quantify cortical bone microstructure using 2D histology, shows its application on a set of 94 samples and compares to 3D methods.</div><div>Fresh frozen human femur pairs from 47 donors aged between 57 and 96 years were obtained from the Medical University of Vienna. Bone samples were cut from 3 sites: proximal part of the diaphysis, inferior and superior segments of the neck. The samples were stained with toluidine blue and imaged under light microscopy. After manual segmentation of a few regions of interest by multiple operators, a convolutional neural network was trained in combination with a random forest for automatic segmentation. The segmentation analysis compares morphology and structure distribution of Haversian canals, osteocyte lacunae, and cement lines with literature, between anatomical sites, sex, left and right sides, and relation to ageing.</div><div>Morphological analysis of the segmentation gives results similar to the literature. Comparison between male and female donors shows no significant differences. There is no significant difference between left and right femur on paired samples but significant differences are observed between anatomical locations. The structures' relative amounts do not present significant changes with age but only weak tendencies. Nevertheless, a strong correlation was observed between osteocyte lacunae density and bone areal fraction.</div><div>This study presents a full process to stain and automatically segment digital cortical bone images. Its application to a large sample set of proximal femora provides strong statistics on the cortical bone structures morphology and distribution. Similarities observed between sides and sexes together with differences observed between sites could indicate that mechanical loading might be a main driver for bone microstructure. Additionally, the relationship between osteocyte lacunae density and bone areal fraction could suggest that bone porosity is regulated by osteocyte survival.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117404"},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Heavy resistance training provides short-term benefits on bone formation in well-functioning older adults 高强度抗阻训练对功能良好的老年人的骨形成有短期的好处。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-18 DOI: 10.1016/j.bone.2025.117393
Mads Bloch-Ibenfeldt , Anne Theil Gates , Niklas Rye Jørgensen , Allan Linneberg , Mette Aadahl , Michael Kjær , Carl-Johan Boraxbekk
<div><h3>Objectives</h3><div>Maintained bone health is critical for independent living when aging. Currently, multimodal exercise regimes including weight-bearing exercises with impact are prescribed as optimal for maintaining bone health, while there is less consensus on the effects of resistance training at different intensities upon bone. Here we examined whether bone health was positively influenced by 1 year of supervised resistance training at two different intensities.</div></div><div><h3>Methods</h3><div>Older adults at retirement age (mean age: 66 ± 3 years, n = 451) were randomized to either 1 year of heavy resistance training (HRT), moderate intensity training (MIT) or a non-exercising control group (CON) in the LISA (LIve active Successful Aging) study. Bone mineral density (BMD) was assessed at whole body level, femoral neck, and the lumbar region of the spine (L1–L4) using Dual-energy X-ray absorptiometry (DXA). Bone degradation and formation were evaluated with blood C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (PINP). Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) was used as a biomarker of functional vitamin K status. Participants were assessed at baseline, immediately following the intervention (year 1), and at longitudinal follow-ups at years 2 and 4. Two-way mixed model ANOVAs were used to assess group differences at all time points.</div></div><div><h3>Results</h3><div>At the 4-year follow-up n = 329 participants (58 % women) remained in the study. BMD was not influenced by training and decreased across all groups over the 4 years for total body (F<sub>3,977</sub> = 4.617, p = 0.003, <span><math><msup><mi>η</mi><mn>2</mn></msup></math></span> = 0.01) and femoral neck both in the dominant (F<sub>3,893</sub> = 45.135, p < 0.001, <span><math><msup><mi>η</mi><mn>2</mn></msup></math></span> = 0.13) and non-dominant leg (F<sub>3,896</sub> = 33.821, p < 0.001, <span><math><msup><mi>η</mi><mn>2</mn></msup></math></span> = 0.10).</div><div>Independent of group, CTX increased (F<sub>3,932</sub> = 47.434, p < 0.001, <span><math><msup><mi>η</mi><mn>2</mn></msup></math></span> = 0.13) over the 4 years. HRT resulted in an increased bone formation (PINP rise) only after the first year with systematic training (t(936) = 3.357, p = 0.04), and it was more pronounced than in CON (t(312) = 2.494, p = 0.04). Plasma dp-ucMGP remained unaltered over time in all groups. In general, women had significantly lower BMD and higher levels of CTX and PINP compared to men.</div></div><div><h3>Conclusion</h3><div>We demonstrated that 1 year of heavy resistance training positively influenced short-term bone formation in well-functioning older adults, although the effect was not maintained at long-term follow ups. These minor changes in bone biomarkers were not reflected in changes in BMD measured with DXA.</div></div><div><h3>Trial registration</h3><div><span><span>clinicaltrials.gov</span><svg><p
目的:保持骨骼健康是老年人独立生活的关键。目前,包括负重运动在内的多模式运动方案被认为是维持骨骼健康的最佳方案,而不同强度的阻力训练对骨骼的影响却鲜有共识。在这里,我们研究了1 年监督下的两种不同强度的阻力训练是否对骨骼健康有积极影响。方法:在LISA (LIve active Successful Aging)研究中,将退休年龄的老年人(平均年龄:66 ± 3 岁,n = 451)随机分为1 年的高强度训练(HRT)、中等强度训练(MIT)或不运动对照组(CON)。采用双能x线骨密度仪(DXA)评估全身水平、股骨颈和腰椎区域(L1-L4)的骨密度(BMD)。采用血I型胶原c末端末端肽(CTX)和I型前胶原n -前肽(PINP)评价骨降解和骨形成。去磷酸化未羧化基质gla蛋白(dp-ucMGP)被用作功能性维生素K状态的生物标志物。参与者在基线、干预后立即(第1年)和第2年和第4年的纵向随访时进行评估。采用双向混合模型方差分析评估各组在各时间点的差异。结果:在4年随访中,n = 329名参与者(58% %为女性)仍在研究中。BMD不会受到培训和减少在所有组4 多年全身(F3,977 = 4.617,p = 0.003,η2 = 0.01)和股骨颈主导(F3,893 = 45.135,p 2 = 0.13)和非惯用的腿(F3,896 = 33.821,p 2 = 0.10)。与组无关,CTX在4 年内增加(f3932 = 47.434,p 2 = 0.13)。HRT仅在系统训练一年后才导致骨形成增加(PINP升高)(t(936) = 3.357,p = 0.04),且比CON (t(312) = 2.494,p = 0.04)更为明显。血浆dp-ucMGP在所有组中保持不变。总的来说,与男性相比,女性的骨密度明显较低,CTX和PINP水平较高。结论:我们证明了1 年的高强度抗阻训练对功能良好的老年人的短期骨形成有积极影响,尽管在长期随访中没有维持这种效果。这些骨生物标志物的微小变化并没有反映在DXA测量的骨密度变化中。试验注册:clinicaltrials.gov (NCT02123641)。
{"title":"Heavy resistance training provides short-term benefits on bone formation in well-functioning older adults","authors":"Mads Bloch-Ibenfeldt ,&nbsp;Anne Theil Gates ,&nbsp;Niklas Rye Jørgensen ,&nbsp;Allan Linneberg ,&nbsp;Mette Aadahl ,&nbsp;Michael Kjær ,&nbsp;Carl-Johan Boraxbekk","doi":"10.1016/j.bone.2025.117393","DOIUrl":"10.1016/j.bone.2025.117393","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;Maintained bone health is critical for independent living when aging. Currently, multimodal exercise regimes including weight-bearing exercises with impact are prescribed as optimal for maintaining bone health, while there is less consensus on the effects of resistance training at different intensities upon bone. Here we examined whether bone health was positively influenced by 1 year of supervised resistance training at two different intensities.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Older adults at retirement age (mean age: 66 ± 3 years, n = 451) were randomized to either 1 year of heavy resistance training (HRT), moderate intensity training (MIT) or a non-exercising control group (CON) in the LISA (LIve active Successful Aging) study. Bone mineral density (BMD) was assessed at whole body level, femoral neck, and the lumbar region of the spine (L1–L4) using Dual-energy X-ray absorptiometry (DXA). Bone degradation and formation were evaluated with blood C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (PINP). Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) was used as a biomarker of functional vitamin K status. Participants were assessed at baseline, immediately following the intervention (year 1), and at longitudinal follow-ups at years 2 and 4. Two-way mixed model ANOVAs were used to assess group differences at all time points.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;At the 4-year follow-up n = 329 participants (58 % women) remained in the study. BMD was not influenced by training and decreased across all groups over the 4 years for total body (F&lt;sub&gt;3,977&lt;/sub&gt; = 4.617, p = 0.003, &lt;span&gt;&lt;math&gt;&lt;msup&gt;&lt;mi&gt;η&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt; = 0.01) and femoral neck both in the dominant (F&lt;sub&gt;3,893&lt;/sub&gt; = 45.135, p &lt; 0.001, &lt;span&gt;&lt;math&gt;&lt;msup&gt;&lt;mi&gt;η&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt; = 0.13) and non-dominant leg (F&lt;sub&gt;3,896&lt;/sub&gt; = 33.821, p &lt; 0.001, &lt;span&gt;&lt;math&gt;&lt;msup&gt;&lt;mi&gt;η&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt; = 0.10).&lt;/div&gt;&lt;div&gt;Independent of group, CTX increased (F&lt;sub&gt;3,932&lt;/sub&gt; = 47.434, p &lt; 0.001, &lt;span&gt;&lt;math&gt;&lt;msup&gt;&lt;mi&gt;η&lt;/mi&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/msup&gt;&lt;/math&gt;&lt;/span&gt; = 0.13) over the 4 years. HRT resulted in an increased bone formation (PINP rise) only after the first year with systematic training (t(936) = 3.357, p = 0.04), and it was more pronounced than in CON (t(312) = 2.494, p = 0.04). Plasma dp-ucMGP remained unaltered over time in all groups. In general, women had significantly lower BMD and higher levels of CTX and PINP compared to men.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;We demonstrated that 1 year of heavy resistance training positively influenced short-term bone formation in well-functioning older adults, although the effect was not maintained at long-term follow ups. These minor changes in bone biomarkers were not reflected in changes in BMD measured with DXA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Trial registration&lt;/h3&gt;&lt;div&gt;&lt;span&gt;&lt;span&gt;clinicaltrials.gov&lt;/span&gt;&lt;svg&gt;&lt;p","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117393"},"PeriodicalIF":3.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcriptome and metabolome analysis of osteoblasts identifies disrupted purine metabolism and parathyroid hormone associated pathway induced by P. gingivalis infection 成骨细胞转录组学和代谢组学分析发现牙龈假单胞菌感染诱导嘌呤代谢中断和甲状旁腺激素相关途径。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-18 DOI: 10.1016/j.bone.2025.117401
Dianbin Liu , Yaoyao Xiang , Mengxin Sun , Jiayi Hu, Qiuchong Chen, Longxiang Liao, Yan Liu, Yanxia Wei
Porphyromonas gingivalis (P. gingivalis), a major pathogenic bacterium of chronic periodontitis and central player in the onset and subsequent progression of periodontitis, can cause alveolar bone resorption. The osteoblast dysfunction induced by P. gingivalis infection is a crucial pathological process causing bone loss. However, the comprehensive responses of osteoblasts, especially metabolism processes involved in osteoblast dysfunction under P. gingivalis invasion are largely unknown. In the present study, to profile the molecules switched in osteoblast dysfunction caused by P. gingivalis infection, the effect of P. gingivalis invasion on osteoblast differentiation was assessed and investigated through transcriptomics and metabolomics approaches. We found that P. gingivalis infection dramatically impaired osteoblast function. P. gingivalis invasion disrupted homeostasis of phosphorus (Pi)/calcium (Ca2+) and induced robust oxidative stress, cell apoptosis and massive activation of inflammatory response in osteoblasts. Notably, the exposure to P. gingivalis induced the inactivation of endocrines pathways, involved in bone formation, which is characterized by downregulated genes and less accumulated metabolites in “Parathyroid hormone synthesis, secretion and action”, its downstream “Wnt signaling pathway” and related Pi/Ca2+ transport. Furthermore, we found that disrupted purine metabolism produced less ATP in P. gingivalis-infected osteoblasts and the reduced ATP may directly inhibit phosphorus transport. Collectively, these results provide a new insight into the molecular changes in P. gingivalis-infected osteoblasts in a comprehensive way.
牙龈卟啉单胞菌(P. gingivalis)是慢性牙周炎的主要病原菌,在牙周炎的发病和随后的进展中起主要作用,可引起牙槽骨吸收。牙龈假单胞菌感染引起的成骨细胞功能障碍是导致骨质流失的重要病理过程。然而,在牙龈假单胞菌侵袭下,成骨细胞的综合反应,特别是参与成骨细胞功能障碍的代谢过程在很大程度上是未知的。本研究通过转录组学和代谢组学方法,研究牙龈假单胞菌侵染对成骨细胞分化的影响,以了解牙龈假单胞菌感染引起成骨细胞功能障碍的分子开关。我们发现牙龈假单胞菌感染会显著损害成骨细胞的功能。牙龈假单胞菌的入侵破坏了成骨细胞中磷(Pi)/钙(Ca2+)的稳态,诱导了强大的氧化应激、细胞凋亡和大量炎症反应的激活。值得注意的是,P. gingivalis暴露导致参与骨形成的内分泌通路失活,其特征是“甲状旁腺激素合成、分泌和作用”及其下游“Wnt信号通路”和相关的Pi/Ca2+运输中基因下调和代谢物积累减少。此外,我们发现在牙龈卟啉卟啉感染的成骨细胞中,嘌呤代谢被破坏产生的ATP减少,减少的ATP可能直接抑制磷的运输。总之,这些结果为全面了解牙龈卟啉卟啉感染成骨细胞的分子变化提供了新的见解。
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引用次数: 0
Real-world safety and effectiveness of romosozumab following daily or weekly administration of teriparatide in primary and secondary osteoporosis 原发性和继发性骨质疏松症患者每日或每周服用特立帕肽后romosozumab的安全性和有效性
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-16 DOI: 10.1016/j.bone.2025.117392
Kazuaki Mineta , Toshihiko Nishisho , Masahiko Okada , Mitsuhiro Kamada , Koichi Sairyo
Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption, and it became available for patients at high risk of osteoporotic fractures in Japan in 2019. The aim of this study was to clarify the clinical effects, safety, and predictors of the effectiveness of 12 months of romosozumab therapy following daily or weekly administration of teriparatide. The study had an observational pre–post design and included 171 female patients. Romosozumab was administered at a dose of 210 mg subcutaneously every 4 weeks for 12 months following daily or weekly administration of teriparatide. The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers were recorded. New fractures occurred in 3 cases (2.2 %). Four patients (2.3 %) with secondary osteoporosis experienced cardiovascular events, which were fatal in 1 patient (0.6 %). The percent changes in BMD at the spine and total hip at 12 months from baseline were + 7.9 % and + 2.4 %, respectively. The percent change in spine BMD did not significantly differ according to whether daily or weekly teriparatide was given as previous treatment. Romosozumab following teriparatide showed greater effectiveness in patients with primary osteoporosis, high P1NP level at 1 month, and low percent changes in TRACP-5b after 12 months of treatment. Romosozumab after treatment with daily or weekly teriparatide was relatively safe and more effective in patients with primary osteoporosis than in those with secondary osteoporosis.
Romosozumab是一种抗硬化蛋白抗体,可增加骨形成,减少骨吸收,2019年在日本开始用于骨质疏松性骨折的高风险患者。本研究的目的是阐明每日或每周服用特立帕肽后12 个月的romosozumab治疗的临床效果、安全性和有效性的预测因素。该研究采用观察性前后设计,包括171名女性患者。Romosozumab在每日或每周给药特立帕肽后,每4 周皮下给药210 mg,持续12 个月。记录新骨折的发生率、安全性、骨密度(BMD)和骨转换指标的变化。新发骨折3例(2.2% %)。4例继发性骨质疏松患者(2.3 %)发生心血管事件,其中1例患者(0.6 %)死亡。从基线到12 个月,脊柱和全髋的骨密度变化百分比分别为 + 7.9 %和 + 2.4 %。脊柱骨密度的百分比变化没有显著差异,无论每日或每周给予特立帕肽作为先前的治疗。特立帕肽后Romosozumab在原发性骨质疏松患者中显示出更大的疗效,1 个月时P1NP水平较高,治疗12 个月后TRACP-5b变化百分比较低。与继发性骨质疏松患者相比,原发性骨质疏松患者接受每日或每周特立帕肽治疗后的Romosozumab相对安全且更有效。
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引用次数: 0
A systematic study of the effect of measurement parameters on determination of osteocyte lacunar properties using laboratory X-ray micro-computed tomography 使用实验室x射线微计算机断层扫描测定骨细胞腔隙特性的测量参数影响的系统研究。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-13 DOI: 10.1016/j.bone.2025.117391
Maja Østergaard, Nina Kølln Wittig, Henrik Birkedal
Accurate 3D characterization of osteocyte lacunae is important when investigating the role of osteocytes under various physiological and pathological conditions but remains a challenge. With the continued development of laboratory X-ray micro-computed tomography, an increasing number of studies employ these techniques beyond traditional bone morphometry to quantify osteocyte lacunae. However, there is a lack of knowledge on the effect of measurement parameters on the image quality and resolution and in turn the osteocyte lacunar quantification. Herein, we have examined the interplay between scan parameters and the resultant lacunar quantification in terms of lacunar size, shape, and density by comparison with a synchrotron benchmark dataset. We summarize our conclusions in a guide for use of μ-CT for osteocyte lacunar quantification: (1) Identification of the measurement requirements to address the research questions. (2) Collection and preparation of suitable sample(s) that fulfills these requirements. (3) Experimental considerations including determination of the required voxel size, in turn dictating the maximum FOV and by extension the maximum size of the sample(s). The experimental parameters chosen should ensure optimal image contrast, sufficient signal to noise, angular sampling etc. Usually, it is advisable to measure as well as possible within the limits of time, budget, data storage and analysis capabilities. (4) Data analysis and reporting of the results, including visual examination of the data at multiple steps in the analysis, to ensure correct feature identification and suitable reporting approaches. (5) Cross study comparisons, which may be unsuitable if the experimental conditions and analysis strategies are not comparable.
在研究骨细胞在各种生理和病理条件下的作用时,准确的骨细胞腔隙三维表征是重要的,但仍然是一个挑战。随着实验室x射线微计算机断层扫描技术的不断发展,越来越多的研究使用这些技术超越传统的骨形态测量来量化骨细胞腔隙。然而,对测量参数对图像质量和分辨率的影响以及骨细胞腔隙定量的影响缺乏了解。在此,我们通过与同步加速器基准数据集的比较,研究了扫描参数与腔隙大小、形状和密度之间的相互作用。我们在μ-CT骨细胞腔隙定量指南中总结了我们的结论:(1)确定测量要求以解决研究问题。(2)收集和制备符合这些要求的合适样品。(3)实验考虑,包括所需体素大小的确定,进而决定最大视场和扩展的最大尺寸的样本。实验参数的选择应保证最佳的图像对比度、足够的信噪比、角度采样等。通常,在时间、预算、数据存储和分析能力的限制下尽可能地度量是明智的。(4)数据分析和报告结果,包括在分析的多个步骤中对数据进行目视检查,以确保正确识别特征和合适的报告方法。(5)交叉研究比较,如果实验条件和分析策略不具有可比性,可能不适合交叉研究比较。
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引用次数: 0
Skeletal and dental tissue mineralization: The potential role of the endoplasmic reticulum/Golgi complex and the endolysosomal and autophagic transport systems 骨骼和牙齿组织矿化:内质网/高尔基复合体、内溶酶体和自噬运输系统的潜在作用。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-13 DOI: 10.1016/j.bone.2025.117390
Irving M. Shapiro , Makarand V. Risbud , Tengteng Tang , William J. Landis
This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there are sound reasons for considering that they may be liberated from mitochondria during the utilization of ATP for anabolic purposes, perhaps linked to matrix synthesis. Published studies indicate that calcium and phosphate ions or their clusters contained as cargo within the intracellular organelles noted above lead to formation of extracellular mineral. The mineral sequestered in mitochondria has been documented as an amorphous calcium phosphate. The ion-, ion cluster- or mineral-containing vesicles exit the cell in plasma membrane blebs, secretory lysosomes or possibly intraluminal vesicles. Such a cell-regulated process provides a means for the rapid transport of ions or mineral particles to the mineralization front of skeletal and dental tissues. Within the extracellular matrix, the ions or mineral may associate to form larger aggregates and potential mineral nuclei, and they may bind to collagen and other proteins. How cells of hard tissues perform their housekeeping and other biosynthetic functions while transporting the very large volumes of ions required for mineralization of the extracellular matrix is far from clear. Addressing this and related questions raised in this review suggests guidelines for further investigations of the intracellular processes promoting the mineralization of the skeletal and dental tissues.
本文综述了内质网/高尔基复合体和细胞内囊泡在介导导致或与脊椎动物组织矿化相关的事件中的潜在作用。钙离子在内质网和高尔基体的小管和腔隙中积累的观察表明,这些细胞器在这一过程中可能具有重要作用。类似水平的钙离子(接近毫摩尔)存在于由核内体、溶酶体和自噬体产生的囊泡中。这些细胞器中磷酸离子的细胞水平也很高(毫摩尔)。虽然这些离子形成矿物质的来源尚未确定,但有充分的理由认为它们可能是在ATP的合成代谢过程中从线粒体中释放出来的,可能与基质合成有关。已发表的研究表明,上文提到的细胞内细胞器内的钙和磷酸盐离子或它们的簇状物作为货物导致细胞外矿物质的形成。封存在线粒体中的矿物质已被证明是一种无定形的磷酸钙。含有离子、离子簇或矿物的囊泡以质膜泡、分泌性溶酶体或可能的腔内囊泡的形式离开细胞。这种细胞调控的过程为离子或矿物颗粒快速运输到骨骼和牙齿组织的矿化前沿提供了一种手段。在细胞外基质中,离子或矿物质可能结合形成更大的聚集体和潜在的矿物核,它们可能与胶原蛋白和其他蛋白质结合。硬组织细胞是如何在运输矿化细胞外基质所需的大量离子的同时,执行其内务管理和其他生物合成功能的,目前尚不清楚。解决这一问题以及本综述中提出的相关问题,为进一步研究促进骨骼和牙齿组织矿化的细胞内过程提供了指导方针。
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引用次数: 0
Impact of prior teriparatide treatment on the effectiveness of romosozumab in patients with postmenopausal osteoporosis: A case-control study 既往特立帕肽治疗对绝经后骨质疏松患者romosozumab疗效的影响:一项病例对照研究。
IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-04 DOI: 10.1016/j.bone.2025.117389
Kosuke Ebina , Tomonori Kobayakawa , Yuki Etani , Takaaki Noguchi , Masafumi Kashii , Gensuke Okamura , Yoshio Nagayama , Hideki Tsuboi , Akira Miyama , Makoto Hirao , Yuji Fukuda , Takuya Kurihara , Atsushi Sugimoto , Ken Nakata , Seiji Okada

Purpose

To evaluate the impact of prior teriparatide (TPTD) treatment on the effectiveness of romosozumab (ROMO) in postmenopausal osteoporosis.

Methods

In this retrospective, case-controlled, multicenter study, 323 postmenopausal patients were initiated ROMO. Of these, 275 were treatment-naïve, and 48 were switched from TPTD, with uninterrupted ROMO treatment for 12 months. Propensity score matching was applied to ensure clinical comparability, yielding 44 patients in each group. Baseline characteristics included a mean age of 78.0 years, lumbar spine (LS) T-score of −3.6, and total hip (TH) T-score of −2.8. Bone mineral density (BMD) and serum bone turnover markers were evaluated over the 12-month period.

Results

The increasing rate in the bone formation marker PINP was significantly greater in the treatment-naïve group compared to the TPTD-switched group throughout the 1–12 month period. Conversely, the reduction in the bone resorption marker TRACP-5b was similar between the groups, indicating a diminished anabolic window in the TPTD-switched group. After 12 months, the TPTD-switched group showed lower BMD gains in the LS (10.3 % vs. 17.3 %; P = 0.002) and TH (3.1 % vs. 7.8 %; P = 0.002) compared to the treatment-naïve group. Multiple regression analysis revealed positive associations between the 12-month percentage BMD increases (LS; β = 0.30; 95 % CI = 0.85–11.61; P = 0.024 / TH; β = 0.32; 95 % CI = 0.51–8.56; P = 0.028) and being treatment-naïve compared to prior TPTD treatment.

Conclusions

Prior TPTD treatment may attenuate the effectiveness of ROMO, potentially due to diminished bone formation activation.
目的:评价既往特立帕肽(TPTD)治疗对罗莫索单抗(romosozumab)治疗绝经后骨质疏松症疗效的影响。方法:在这项回顾性、病例对照、多中心研究中,323例绝经后患者接受了ROMO治疗。其中275例为treatment-naïve, 48例从TPTD转为不间断ROMO治疗12 个月。采用倾向评分匹配确保临床可比性,每组44例。基线特征包括平均年龄78.0 岁,腰椎(LS) t评分为-3.6,全髋关节(TH) t评分为-2.8。在12个月期间评估骨密度(BMD)和血清骨转换指标。结果:在1-12 个月期间,treatment-naïve组骨形成标志物PINP的增加率明显高于tppd切换组。相反,骨吸收标志物TRACP-5b的减少在两组之间相似,表明tppd开关组的合成代谢窗口减少。12 个月后,tppd切换组在LS中显示出较低的骨密度增加(10.3 % vs. 17.3 %;P = 0.002)和TH(3.1 % vs. 7.8 %;P = 0.002)与treatment-naïve组比较。多元回归分析显示,12个月骨密度增加百分比(LS;β = 0.30;95 % CI = 0.85 - -11.61;P = 0.024 / th;β = 0.32;95 % CI = 0.51 - -8.56;P = 0.028),与之前的TPTD治疗相比为treatment-naïve。结论:先前的TPTD治疗可能会减弱ROMO的有效性,可能是由于骨形成激活减少。
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引用次数: 0
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