Bone Reports最新文献

Bone mechanical loading reduces heart rate and increases heart rate variability in mice

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-04-16 DOI: 10.1016/j.bonr.2025.101844

Julian A. Vallejo , Mark Gray , Jackson Klump , Andrew Wacker , Mark Dallas , Mark L. Johnson , Michael J. Wacker

Cardiovascular disease and osteoporosis are clinically associated. Bone adapts to mechanical forces by altering its overall structure and mass. In response to mechanical strain bone cells release signaling molecules and activate the nervous system. Bone also exhibits endocrine functions that modulate a number of tissues including the heart. We hypothesized that bone mechanical loading acutely alters cardiac function via neural and/or endocrine mechanisms. To test this hypothesis, we performed in vivo tibia mechanical loading in anesthetized mice while monitoring heart parameters using electrocardiogram (ECG). An immediate, transient reduction in resting heart rate was observed during tibial loading in both adult male and female mice (p < 0.01) with concurrent increases in heart rate variability (HRV) (p < 0.01). ECG intervals, PR, QRS and QTc were unaffected with loading. In further studies, we found that at least 3 N of load was necessary to elicit this heart response in adult mice. With aging to 11–12 months the responsiveness of the heart to loading was blunted, suggesting this bone-heart connection may weaken with age. Administration of lidocaine around the tibia significantly diminished the heart rate response to bone loading (p < 0.05). Moreover, pre-treatment with sympathetic antagonist propranolol inhibited this heart rate response to loading (p < 0.05), while parasympathetic antagonist atropine did not (p > 0.05). This suggests that a neuronal afferent pathway in the hindlimb and reduction in efferent sympathetic tone mediate this bone-neuro-heart reflex. In conclusion, the findings that tibia bone loading age-dependently modulates heart function support the concept of physiological coupling of the skeletal and cardiovascular systems.

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引用次数: 0

A rat traumatized shoulder model for the study of post-surgical adhesions

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-04-14 DOI: 10.1016/j.bonr.2025.101843

Yael Milgrom , Aharon S. Finestone , Charles Milgrom

A third of patients after open reduction and plating of proximal humerus fractures require subsequent plate removal principally because of adhesions which occur between the deep surface of the deltoid and fracture fixation zone and limit shoulder motion. A rat model of post-surgical shoulder adhesions was developed using a deltoid split approach commonly used in proximal humerus fracture surgery, with trauma induced by a straight diamond nasal rasp to the undersurface of the deltoid and supraspinatus tendon and adjoining proximal humerus. Using the model, the traumatized limb of 12 animals treated with an alginate mimetic injected into the wound before closure and 9 untreated animals were immobilized for 9 ± 1 days and then their passive range of shoulder flexion-extension measured, followed by histopathology examination. The total passive range of shoulder flexion-extension of 120 degrees in the alginate treated group was greater than the 84 degrees in the untreated group (p = 0.0043). The mean periosteal fibrotic capsule width in the injured area of untreated animals (515 ± 449 μm) was greater than that of animals treated with alginate (186 ± 180 μm, p = 0.003). Untreated animals had severe, grade 4 fibrosis and collagen deposition, and granulation tissue, while treated animals had mild grade 1 responses. The animal model developed produced limited shoulder motion and associated fibrotic changes. It can be used to evaluate potential treatments designed to prevent adhesions that develop after plating of proximal humeral fractures.

{"title":"A rat traumatized shoulder model for the study of post-surgical adhesions","authors":"Yael Milgrom , Aharon S. Finestone , Charles Milgrom","doi":"10.1016/j.bonr.2025.101843","DOIUrl":"10.1016/j.bonr.2025.101843","url":null,"abstract":"<div><div>A third of patients after open reduction and plating of proximal humerus fractures require subsequent plate removal principally because of adhesions which occur between the deep surface of the deltoid and fracture fixation zone and limit shoulder motion. A rat model of post-surgical shoulder adhesions was developed using a deltoid split approach commonly used in proximal humerus fracture surgery, with trauma induced by a straight diamond nasal rasp to the undersurface of the deltoid and supraspinatus tendon and adjoining proximal humerus. Using the model, the traumatized limb of 12 animals treated with an alginate mimetic injected into the wound before closure and 9 untreated animals were immobilized for 9 ± 1 days and then their passive range of shoulder flexion-extension measured, followed by histopathology examination. The total passive range of shoulder flexion-extension of 120 degrees in the alginate treated group was greater than the 84 degrees in the untreated group (p = 0.0043). The mean periosteal fibrotic capsule width in the injured area of untreated animals (515 ± 449 μm) was greater than that of animals treated with alginate (186 ± 180 μm, p = 0.003). Untreated animals had severe, grade 4 fibrosis and collagen deposition, and granulation tissue, while treated animals had mild grade 1 responses. The animal model developed produced limited shoulder motion and associated fibrotic changes. It can be used to evaluate potential treatments designed to prevent adhesions that develop after plating of proximal humeral fractures.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101843"},"PeriodicalIF":2.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838506","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

The effect of acupuncture on reducing postoperative complications in fracture patients: A retrospective analysis using the TriNetX database

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-04-04 DOI: 10.1016/j.bonr.2025.101842

Yi-Pin Chang , Hsin-Hua Chen , Jui-Ju Tseng , Chia-I Tsai

Background

Bone fracture is a common orthopedic condition that affects millions of people worldwide. The management frequently involves surgery, which requires hospitalization. Patients with fractures often have a risk of developing complications, including pain, inflammation, infection, delayed healing, thrombosis, and organ failure. Acupuncture is widely used for conditions such as pain, respiratory issues, urinary system disorders, and gastrointestinal discomfort.

Methods

In this retrospective study, we evaluated the effectiveness of acupuncture in reducing postoperative complications in fracture patients. Using the TriNetX platform, we identified individuals hospitalized for their first fracture surgery and performed 1: 1 propensity score matching. Patients who received three or more acupuncture treatments within one week (n = 433) were compared to those who received none (n = 433), with matching based on age, sex, race, BMI, comorbidities, and medications (standardized mean differences). Postoperative complications within 180 days were analyzed using risk percentages, risk ratios, odds ratios, Kaplan-Meier analysis with log-rank tests, and hazard ratios, all reported with 95 % confidence intervals and P-values.

Results

Fourteen patients in the acupuncture group experienced respiratory failure with a risk of 3.2 %, while 29 patients in the non-acupuncture group developed respiratory failure with a risk of 6.7 %. The risk ratio was 0.48 (95 % CI 0.26–0.90) and the OR was 0.47 (95 % CI 0.24–0.89). The Kaplan-Meier analysis found a significantly higher survival probability in the acupuncture group (log-rank test P = 0.01; HR 0.44, 95%CI 0.23–0.83).

Conclusions

Acupuncture appeared to have the potential to reduce postoperative complications in bone fracture patients. Further large-scale studies are needed to provide stronger evidence.

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引用次数: 0

Ribosylation-induced increase in advanced glycation end products has limited impacts on mechanical properties in human cortical bone

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-04-02 DOI: 10.1016/j.bonr.2025.101841

Katelynn R. Gallagher, Olivia N. White, Andrew A. Tomaschke, Dyann M. Segvich, Joseph M. Wallace

Diabetes affects over 38 million individuals in the U.S. and is associated with a heightened risk of fractures despite normal or elevated bone mineral density (BMD). This increased fracture susceptibility may be linked to the accumulation of advanced glycation end products (AGEs), which are theorized to compromise bone quality by stiffening the collagen network, leading to tissue embrittlement. In this study, the mechanical effects of AGE accumulation in human cortical bone were evaluated in vitro. Bone beams, derived from a human femur, were incubated in a ribose solution to induce AGE accumulation, while control beams were incubated in a control solution. Dynamic Mechanical Analysis (DMA) and three-point bending tests were conducted to assess the mechanical properties of the bone beams. Fluorescent AGE analysis was performed to quantify and compare AGE levels between the groups. The study found no significant differences in mechanical properties between the control and ribose-treated groups, despite a significant elevation in normalized AGE content in the ribose group. These results suggest that AGE accumulation may have a weaker impact on the mechanical properties of human bone than previously hypothesized. However, this study emphasizes the need for further research to explore the relationship between AGE accumulation and bone quality. Understanding this relationship is crucial for developing strategies to reduce fracture risk in populations with high AGE levels, such as diabetic and elderly individuals.

{"title":"Ribosylation-induced increase in advanced glycation end products has limited impacts on mechanical properties in human cortical bone","authors":"Katelynn R. Gallagher, Olivia N. White, Andrew A. Tomaschke, Dyann M. Segvich, Joseph M. Wallace","doi":"10.1016/j.bonr.2025.101841","DOIUrl":"10.1016/j.bonr.2025.101841","url":null,"abstract":"<div><div>Diabetes affects over 38 million individuals in the U.S. and is associated with a heightened risk of fractures despite normal or elevated bone mineral density (BMD). This increased fracture susceptibility may be linked to the accumulation of advanced glycation end products (AGEs), which are theorized to compromise bone quality by stiffening the collagen network, leading to tissue embrittlement. In this study, the mechanical effects of AGE accumulation in human cortical bone were evaluated <em>in vitro</em>. Bone beams, derived from a human femur, were incubated in a ribose solution to induce AGE accumulation, while control beams were incubated in a control solution. Dynamic Mechanical Analysis (DMA) and three-point bending tests were conducted to assess the mechanical properties of the bone beams. Fluorescent AGE analysis was performed to quantify and compare AGE levels between the groups. The study found no significant differences in mechanical properties between the control and ribose-treated groups, despite a significant elevation in normalized AGE content in the ribose group. These results suggest that AGE accumulation may have a weaker impact on the mechanical properties of human bone than previously hypothesized. However, this study emphasizes the need for further research to explore the relationship between AGE accumulation and bone quality. Understanding this relationship is crucial for developing strategies to reduce fracture risk in populations with high AGE levels, such as diabetic and elderly individuals.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101841"},"PeriodicalIF":2.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769110","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

Intake of eggshell membrane enhances bone mass and suppresses bone marrow adiposity in normal growing rats

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-04-01 DOI: 10.1016/j.bonr.2025.101840

Nao Yashima , Kaoru Fujikawa , Wataru Minamizono , Hiroya Matsunaga , Jiazheng Lyu , Hirai Suito , Takumi Okunuki , Shingo Nakai , Masafumi Ohsako

Eggshell membrane intake is considered to have beneficial effects on bone health; however, relevant evidence remains scant. Therefore, we aimed to explore the direct effects of eggshell membrane intake on osteogenic function in normal growing rats. Six-week-old male Wistar rats were divided into control (CO) and eggshell membrane (EM) groups. The experiment was conducted over 8 weeks. Visual observation and micro-computed tomography analysis revealed a significant increase in bone mass in the EM group compared with that in the CO group. Histological analysis showed thick and long trabeculae in the EM group, accompanied by an increase in the number of osteoblasts and suppression of adipocyte accumulation. Furthermore, Col1a1 expression was significantly higher in the EM group than in the CO group, although no significant differences were found in the number of TRAP-positive osteoclasts or Ctsk expression. Immunohistochemical analysis demonstrated a notable increase in the number of Col1-positive osteoblasts but a significant decrease in the number of Dlk1-positive adipocytes in the EM group. Gene expression analysis revealed no difference in the expression of Runx2 (the master regulator of osteoblast differentiation) between the groups. However, the expression of Sp7, which functions downstream of Runx2, was significantly upregulated, whereas that of Pparg, the master regulator of adipocyte differentiation, was significantly downregulated in the EM group compared with those in the CO group. Overall, the intake of eggshell membranes may enhance osteogenic function and suppress bone marrow adiposity. These findings support the beneficial effects of eggshell membrane intake on bone health.

{"title":"Intake of eggshell membrane enhances bone mass and suppresses bone marrow adiposity in normal growing rats","authors":"Nao Yashima , Kaoru Fujikawa , Wataru Minamizono , Hiroya Matsunaga , Jiazheng Lyu , Hirai Suito , Takumi Okunuki , Shingo Nakai , Masafumi Ohsako","doi":"10.1016/j.bonr.2025.101840","DOIUrl":"10.1016/j.bonr.2025.101840","url":null,"abstract":"<div><div>Eggshell membrane intake is considered to have beneficial effects on bone health; however, relevant evidence remains scant. Therefore, we aimed to explore the direct effects of eggshell membrane intake on osteogenic function in normal growing rats. Six-week-old male Wistar rats were divided into control (CO) and eggshell membrane (EM) groups. The experiment was conducted over 8 weeks. Visual observation and micro-computed tomography analysis revealed a significant increase in bone mass in the EM group compared with that in the CO group. Histological analysis showed thick and long trabeculae in the EM group, accompanied by an increase in the number of osteoblasts and suppression of adipocyte accumulation. Furthermore, <em>Col1a1</em> expression was significantly higher in the EM group than in the CO group, although no significant differences were found in the number of TRAP-positive osteoclasts or <em>Ctsk</em> expression. Immunohistochemical analysis demonstrated a notable increase in the number of Col1-positive osteoblasts but a significant decrease in the number of Dlk1-positive adipocytes in the EM group. Gene expression analysis revealed no difference in the expression of <em>Runx2</em> (the master regulator of osteoblast differentiation) between the groups. However, the expression of <em>Sp7</em>, which functions downstream of <em>Runx2</em>, was significantly upregulated, whereas that of <em>Pparg</em>, the master regulator of adipocyte differentiation, was significantly downregulated in the EM group compared with those in the CO group. Overall, the intake of eggshell membranes may enhance osteogenic function and suppress bone marrow adiposity. These findings support the beneficial effects of eggshell membrane intake on bone health.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101840"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748582","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

Can AI reveal the next generation of high-impact bone genomics targets?

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-03-24 DOI: 10.1016/j.bonr.2025.101839

Casey S. Greene , Christopher R. Gignoux , Marc Subirana-Granés , Milton Pividori , Stephanie C. Hicks , Cheryl L. Ackert-Bicknell

Genetic studies have revealed hundreds of loci associated with bone-related phenotypes, including bone mineral density (BMD) and fracture risk. However, translating discovered loci into effective new therapies remains challenging. We review success stories including PCSK9-related drugs in cardiovascular disease and evidence supporting the use of human genetics to guide drug discovery, while highlighting advances in artificial intelligence and machine learning with the potential to improve target discovery in skeletal biology. These strategies are poised to improve how we integrate diverse data types, from genetic and electronic health records data to single-cell profiles and knowledge graphs. Such emerging computational methods can position bone genomics for a future of more precise, effective treatments, ultimately improving the outcomes for patients with common and rare skeletal disorders.

引用次数: 0

Bone mineral density and microarchitecture improvement in a young patient with Hajdu-Cheney syndrome and autosomal dominant polycystic kidney disease treated with alendronate

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-03-24 DOI: 10.1016/j.bonr.2025.101838

André Silva Franco , Valeria de Falco Caparbo , Elieser Hitoshi Watanabe , Rosa Maria Rodrigues Pereira , Luiz Fernando Onuchic

Introduction

Osteoporosis, typically seen in postmenopausal women, can also affect younger individuals, a condition known as Early-Onset Osteoporosis (EOOP). EOOP may be secondary to various conditions or arise from rare genetic disorders such as Hajdu-Cheney Syndrome (HCS), characterized by systemic bone involvement and fragility fractures.

Case Report

A 14-year-old male presented with a distal left femur fragility fracture. His medical history included spina bifida and bilateral tarsal coalition, with no family history of osteoporosis, and polycystic kidneys associated with a positive family history of autosomal dominant polycystic kidney disease (ADPKD). Laboratory tests were unremarkable, but dual X-ray absorptiometry (DXA) revealed low bone mineral density (BMD), and high resolution peripheral quantitative computed tomography (HR-pQCT) showed decreased volumetric bone density (vBMD), particularly in the cortical bone. At age 17, his kidneys were cystic and mildly enlarged. Whole exome sequencing revealed a pathogenic variant in NOTCH2, confirming the diagnosis of HCS, and a very likely causative variant in PKD1, supporting the diagnosis of ADPKD.

The treatment regimen included weekly alendronate, impact exercise, a calcium-rich diet, and vitamin D supplementation. After 3 years, follow-up DXA and HR-pQCT demonstrated significant improvements in BMD and vBMD, mainly in the cortical bone.

Discussion

This case highlights the effectiveness of alendronate in managing osteoporosis in a patient with HCS and ADPKD, despite the current lack of strong supportive evidence. Long-term monitoring revealed substantial improvements in bone density and microarchitecture, underscoring the importance of early diagnosis and intervention for genetic causes of osteoporosis to prevent fracture-related morbidity.

{"title":"Bone mineral density and microarchitecture improvement in a young patient with Hajdu-Cheney syndrome and autosomal dominant polycystic kidney disease treated with alendronate","authors":"André Silva Franco , Valeria de Falco Caparbo , Elieser Hitoshi Watanabe , Rosa Maria Rodrigues Pereira , Luiz Fernando Onuchic","doi":"10.1016/j.bonr.2025.101838","DOIUrl":"10.1016/j.bonr.2025.101838","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis, typically seen in postmenopausal women, can also affect younger individuals, a condition known as Early-Onset Osteoporosis (EOOP). EOOP may be secondary to various conditions or arise from rare genetic disorders such as Hajdu-Cheney Syndrome (HCS), characterized by systemic bone involvement and fragility fractures.</div></div><div><h3>Case Report</h3><div>A 14-year-old male presented with a distal left femur fragility fracture. His medical history included spina bifida and bilateral tarsal coalition, with no family history of osteoporosis, and polycystic kidneys associated with a positive family history of autosomal dominant polycystic kidney disease (ADPKD). Laboratory tests were unremarkable, but dual X-ray absorptiometry (DXA) revealed low bone mineral density (BMD), and high resolution peripheral quantitative computed tomography (HR-pQCT) showed decreased volumetric bone density (vBMD), particularly in the cortical bone. At age 17, his kidneys were cystic and mildly enlarged. Whole exome sequencing revealed a pathogenic variant in <em>NOTCH2</em>, confirming the diagnosis of HCS, and a very likely causative variant in <em>PKD1</em>, supporting the diagnosis of ADPKD.</div><div>The treatment regimen included weekly alendronate, impact exercise, a calcium-rich diet, and vitamin D supplementation. After 3 years, follow-up DXA and HR-pQCT demonstrated significant improvements in BMD and vBMD, mainly in the cortical bone.</div></div><div><h3>Discussion</h3><div>This case highlights the effectiveness of alendronate in managing osteoporosis in a patient with HCS and ADPKD, despite the current lack of strong supportive evidence. Long-term monitoring revealed substantial improvements in bone density and microarchitecture, underscoring the importance of early diagnosis and intervention for genetic causes of osteoporosis to prevent fracture-related morbidity.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101838"},"PeriodicalIF":2.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697921","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

Mild antiresorptive activity of an anti-vascular endothelial growth factor A antibody and sunitinib in a rat model of bone resorption

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-03-17 DOI: 10.1016/j.bonr.2025.101837

J.I. Aguirre, S.M. Croft, E.J. Castillo, C.J. Cruz-Camacho, D.B. Kimmel

Medication-Related-Osteonecrosis-of-the-Jaw (MRONJ) is an adverse event linked to antiresorptives such as bisphosphonates and denosumab. While MRONJ predominantly affects cancer patients treated with these agents, it has been less frequently reported in cancer patients receiving angiogenesis inhibitors (AgIs) like bevacizumab and sunitinib, even without concurrent use of antiresorptives. We hypothesized that certain AgIs exhibit antiresorptive activity in addition to their antiangiogenic effects, potentially influencing the pathophysiology of MRONJ.

52 five-week-old SD rats were randomized to receive vehicle (VEH), an oncologic dose of zoledronic acid (ZOL), or low (LD) and high doses (HD) of either an anti-VEGFA antibody or sunitinib (SU) for 10 days. We used the Schenk assay to assess the in vivo antiresorptive properties of these drugs/agents. We evaluated serum biomarkers of bone resorption (TRACP 5b) and formation (P1NP), pQCT variables of the femurs/tibias, and bone resorption/formation variables by bone histomorphometry at the distal femur metaphysis.

ZOL reduced TRACP-5b levels, osteoclast number, and BFR while increasing vBMD, mineralized tissue volume, calcified cartilage volume, and bone volume. Both anti-VEGFA and SU decreased osteoclast number and increased calcified cartilage volume relative to total mineralized tissue volume, though to a lesser extent than ZOL. Anti-VEGFA (HD) also reduced TRACP-5b levels. Furthermore, both AgIs decreased P1NP levels, MAR, and bone elongation rate but increased growth cartilage thickness and induced physeal dysplasia.

In conclusion, AgIs, particularly anti-VEGFA, exhibit significant yet milder antiresorptive activity compared to ZOL. They also affect bone formation, suggesting a complex mechanism that may play a role in the pathophysiology of MRONJ.

{"title":"Mild antiresorptive activity of an anti-vascular endothelial growth factor A antibody and sunitinib in a rat model of bone resorption","authors":"J.I. Aguirre, S.M. Croft, E.J. Castillo, C.J. Cruz-Camacho, D.B. Kimmel","doi":"10.1016/j.bonr.2025.101837","DOIUrl":"10.1016/j.bonr.2025.101837","url":null,"abstract":"<div><div>Medication-Related-Osteonecrosis-of-the-Jaw (MRONJ) is an adverse event linked to antiresorptives such as bisphosphonates and denosumab. While MRONJ predominantly affects cancer patients treated with these agents, it has been less frequently reported in cancer patients receiving angiogenesis inhibitors (AgIs) like bevacizumab and sunitinib, even without concurrent use of antiresorptives. We <em>hypothesized</em> that certain AgIs exhibit antiresorptive activity in addition to their antiangiogenic effects, potentially influencing the pathophysiology of MRONJ.</div><div>52 five-week-old SD rats were randomized to receive vehicle (VEH), an oncologic dose of zoledronic acid (ZOL), or low (LD) and high doses (HD) of either an anti-VEGFA antibody or sunitinib (SU) for 10 days. We used the Schenk assay to assess the <em>in vivo</em> antiresorptive properties of these drugs/agents. We evaluated serum biomarkers of bone resorption (TRACP 5b) and formation (P1NP), pQCT variables of the femurs/tibias, and bone resorption/formation variables by bone histomorphometry at the distal femur metaphysis.</div><div>ZOL reduced TRACP-5b levels, osteoclast number, and BFR while increasing vBMD, mineralized tissue volume, calcified cartilage volume, and bone volume. Both anti-VEGFA and SU decreased osteoclast number and increased calcified cartilage volume relative to total mineralized tissue volume, though to a lesser extent than ZOL. Anti-VEGFA (HD) also reduced TRACP-5b levels. Furthermore, both AgIs decreased P1NP levels, MAR, and bone elongation rate but increased growth cartilage thickness and induced physeal dysplasia.</div><div>In conclusion, AgIs, particularly anti-VEGFA, exhibit significant yet milder antiresorptive activity compared to ZOL. They also affect bone formation, suggesting a complex mechanism that may play a role in the pathophysiology of MRONJ.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101837"},"PeriodicalIF":2.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642223","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

Chronic heavy alcohol consumption impairs the ability of demineralized allogenic bone matrix to support osteoinduction in alcohol-naïve rats

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-03-12 DOI: 10.1016/j.bonr.2025.101836

Russell T. Turner , Amida F. Kuah , Cynthia H. Trevisiol , Kathy S. Howe , Adam J. Branscum , Urszula T. Iwaniec

Allografts play an important role in treatment of complex bone fractures and deformities. The purpose of this study was to test the hypothesis that alcohol consumption impairs graft incorporation and bone healing by two mechanisms: (1) by lowering osteoinductive capacity and (2) by suppressing bone formation. We performed experiments using a demineralized allogeneic bone matrix (DBM) model in which DBM harvested from donor rats fed control or ethanol diet was implanted subcutaneously into recipient rats fed control or ethanol diet. We also evaluated the efficacy of intermittent parathyroid hormone (PTH) on bone graft incorporation (DBM from donor rats fed alcohol or control diet) using a critical size defect model. Bone formed during osteoinduction was measured by micro-computed tomography. Experiment 1: Bone volume was lower in DBM harvested from ethanol-consuming donors 6 weeks following implantation into recipients fed control diet, indicating that exposure of the donor rats to ethanol lowered osteoinductive capacity. Experiment 2: Bone volume was lower in DBM harvested 3 weeks following implantation from ethanol-consuming donors into ethanol-consuming recipients compared to DBM harvested from control donors implanted into control recipients or DBM harvested from control donors implanted into ethanol-consuming recipients. Experiment 3: Ethanol consumption by donors resulted in a tendency for lower DBM bone volume (p = 0.085) whereas PTH treatment resulted in higher DBM bone volume in the critical size defect model. Our results suggest that chronic heavy alcohol consumption by allograft donors may impair osteoinduction and this negative outcome may be worsened by alcohol intake during bone healing. Additionally, PTH has the potential to increase osteoinduction in DBM harvested from both abstinent and alcohol-consuming donors.

{"title":"Chronic heavy alcohol consumption impairs the ability of demineralized allogenic bone matrix to support osteoinduction in alcohol-naïve rats","authors":"Russell T. Turner , Amida F. Kuah , Cynthia H. Trevisiol , Kathy S. Howe , Adam J. Branscum , Urszula T. Iwaniec","doi":"10.1016/j.bonr.2025.101836","DOIUrl":"10.1016/j.bonr.2025.101836","url":null,"abstract":"<div><div>Allografts play an important role in treatment of complex bone fractures and deformities. The purpose of this study was to test the hypothesis that alcohol consumption impairs graft incorporation and bone healing by two mechanisms: (1) by lowering osteoinductive capacity and (2) by suppressing bone formation. We performed experiments using a demineralized allogeneic bone matrix (DBM) model in which DBM harvested from donor rats fed control or ethanol diet was implanted subcutaneously into recipient rats fed control or ethanol diet. We also evaluated the efficacy of intermittent parathyroid hormone (PTH) on bone graft incorporation (DBM from donor rats fed alcohol or control diet) using a critical size defect model. Bone formed during osteoinduction was measured by micro-computed tomography. <u>Experiment 1</u>: Bone volume was lower in DBM harvested from ethanol-consuming donors 6 weeks following implantation into recipients fed control diet, indicating that exposure of the donor rats to ethanol lowered osteoinductive capacity. <u>Experiment 2</u>: Bone volume was lower in DBM harvested 3 weeks following implantation from ethanol-consuming donors into ethanol-consuming recipients compared to DBM harvested from control donors implanted into control recipients or DBM harvested from control donors implanted into ethanol-consuming recipients. <u>Experiment 3</u>: Ethanol consumption by donors resulted in a tendency for lower DBM bone volume (<em>p</em> = 0.085) whereas PTH treatment resulted in higher DBM bone volume in the critical size defect model. Our results suggest that chronic heavy alcohol consumption by allograft donors may impair osteoinduction and this negative outcome may be worsened by alcohol intake during bone healing. Additionally, PTH has the potential to increase osteoinduction in DBM harvested from both abstinent and alcohol-consuming donors.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101836"},"PeriodicalIF":2.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632198","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

The biological function of integrin-linked kinase on bone formation

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2025-03-10 DOI: 10.1016/j.bonr.2025.101834

Yu-ling Liu , Yue-ming Mei , Jing-qiong Xun , Zhuo-yue Lv , Qian He , Zhou-bo-ran Liu , Lin Li , Fen Xie , Ru-chun Dai

Bone remodeling process is the basis for maintaining normal bone microstructure and promoting fracture repair. Recent studies have proven that integrins can promote bone formation and fracture repair. Integrin-linked kinase (ILK), as the proximal effector of the integrin receptor, is a key protein factor linking integrin and cytoskeleton. It is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system. At present, the regulation effect of ILK in bone formation attracts the attention of researchers. This review emphasizes that ILK as a key molecule affects the functions of bone marrow stromal cells (BMSCs) and osteoblasts, and regulates bone formation. Additionally, ILK plays a key role in the process of“angiogenic–osteogenic coupling ”. The present role of ILK in the pathogenesis of osteoporosis is also described. Strategies that target ILK may as a new prospective treatment for osteoporosis (OP).

{"title":"The biological function of integrin-linked kinase on bone formation","authors":"Yu-ling Liu , Yue-ming Mei , Jing-qiong Xun , Zhuo-yue Lv , Qian He , Zhou-bo-ran Liu , Lin Li , Fen Xie , Ru-chun Dai","doi":"10.1016/j.bonr.2025.101834","DOIUrl":"10.1016/j.bonr.2025.101834","url":null,"abstract":"<div><div>Bone remodeling process is the basis for maintaining normal bone microstructure and promoting fracture repair. Recent studies have proven that integrins can promote bone formation and fracture repair. Integrin-linked kinase (ILK), as the proximal effector of the integrin receptor, is a key protein factor linking integrin and cytoskeleton. It is involved in crucial cellular processes including proliferation, survival, differentiation, migration, invasion, and angiogenesis reflects on systemic changes in the kidney, heart, muscle, skin, and vascular system. At present, the regulation effect of ILK in bone formation attracts the attention of researchers. This review emphasizes that ILK as a key molecule affects the functions of bone marrow stromal cells (BMSCs) and osteoblasts, and regulates bone formation. Additionally, ILK plays a key role in the process of“angiogenic–osteogenic coupling ”. The present role of ILK in the pathogenesis of osteoporosis is also described. Strategies that target ILK may as a new prospective treatment for osteoporosis (OP).</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101834"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609277","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