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Prevention of glucocorticoid-induced impairment of bone metabolism-a randomized, placebo-controlled, single centre proof-of-concept clinical trial. 预防糖皮质激素引起的骨代谢损伤——一项随机、安慰剂对照、单中心概念验证临床试验。
IF 3.4
JBMR Plus Pub Date : 2025-02-17 eCollection Date: 2025-04-01 DOI: 10.1093/jbmrpl/ziaf031
Giulia Gregori, Lisa Johansson, Lena Silberberg, Henrik Imberg, Per Magnusson, Marcus Lind, Mattias Lorentzon
{"title":"Prevention of glucocorticoid-induced impairment of bone metabolism-a randomized, placebo-controlled, single centre proof-of-concept clinical trial.","authors":"Giulia Gregori, Lisa Johansson, Lena Silberberg, Henrik Imberg, Per Magnusson, Marcus Lind, Mattias Lorentzon","doi":"10.1093/jbmrpl/ziaf031","DOIUrl":"10.1093/jbmrpl/ziaf031","url":null,"abstract":"<p><p>Oral glucocorticoid (GC) therapy rapidly and deleteriously affects bone metabolism and blood glucose regulation. The gut microbiota regulates bone metabolism and a prior study found that <i>Limosilactobacillus reuteri</i> ATCC PTA6475 (<i>L. reuteri</i>) reduced bone loss over 12 mo in older women<i>.</i> Mice treated either with broad-spectrum antibiotics or with <i>L. reuteri</i> did not experience GC-induced trabecular bone loss. This proof-of-concept, randomized, double-blind, placebo-controlled trial aimed to investigate if daily supplementation with <i>L. reuteri</i>, compared with placebo, could mitigate or prevent the negative effects of oral GC on bone turnover and blood glucose regulation in healthy young adults. Twenty-one men and 29 women, aged 18-45, were randomized to either placebo or <i>L. reuteri</i> (1 × 10<sup>10</sup> CFU/d) treatment for 2 wk, followed by open-label oral prednisolone 25 mg daily for 7 d. Primary outcomes were changes in blood bone status indices (osteocalcin, C-terminal telopeptide cross-links of collagen type-I (CTX), and type-I procollagen intact N-terminal propeptide [PINP]) from baseline to 7 d after starting oral GC. Secondary endpoints included changes in blood glucose levels using continuous glucose monitoring during the same period (ClinicalTrials.gov NCT04767711). Blood samples were collected from participants in the morning after overnight fasting. Forty-six participants completed the 30-d study. The <i>L. reuteri</i> and placebo groups were well balanced in terms of baseline characteristics (age, BMI, sex, dietary intake, and physical activity). No significant differences were found between <i>L. reuteri</i> vs placebo for percent changes in CTX (-0.3 [95%CI -19.2-18.7], <i>p</i> = .98) or PINP (4.2 [-6.3-14.8], <i>p</i> = .43), or in osteocalcin levels (14.2 [-7.8-36.3], <i>p</i> = .21), although the group-to-group difference in osteocalcin was larger. There was no effect of treatment on mean blood glucose (-0.1 [-0.3-0.1] mmol/L, <i>p</i> = .28). In conclusion, we failed to detect a significant effect of <i>L. reuteri</i> supplementation on GC-related adverse effects on bone status indices in this proof-of-concept RCT. Larger studies are needed to identify any potential smaller effects.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 4","pages":"ziaf031"},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752743","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
Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice. 空间组织形态测量显示,局部周围神经调节,但不是骨骼适应施加负荷所必需的小鼠。
IF 3.4
JBMR Plus Pub Date : 2025-01-12 eCollection Date: 2025-03-01 DOI: 10.1093/jbmrpl/ziaf006
Alec T Beeve, Mohamed G Hassan, Anna Li, Nicole Migotsky, Matthew J Silva, Erica L Scheller
{"title":"Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice.","authors":"Alec T Beeve, Mohamed G Hassan, Anna Li, Nicole Migotsky, Matthew J Silva, Erica L Scheller","doi":"10.1093/jbmrpl/ziaf006","DOIUrl":"10.1093/jbmrpl/ziaf006","url":null,"abstract":"<p><p>Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their role in the bone anabolic response remains controversial. We hypothesized that spatial alignment of periosteal nerves with sites of load-induced bone formation would clarify this relationship. To achieve this, we developed RadialQuant, a custom tool for spatial histomorphometry. Tibiae of control and neurectomized (sciatic/femoral nerve cut) pan-neuronal Baf53b-tdTomato reporter mice were loaded for 5 days. Bone formation and periosteal nerve axon density were then quantified simultaneously in non-decalcified sections of the mid-diaphysis using RadialQuant. In control animals, anabolic loading induced maximal periosteal bone formation at the site of peak compression, as has been reported previously. By contrast, loading did not significantly change overall periosteal nerve density. Neurectomy depleted ~90% of all periosteal axons, with near-total depletion on load-responsive surfaces. Neurectomy alone also caused de novo bone formation on the lateral aspect of the mid-diaphysis. However, neurectomy did not inhibit load-induced increases in periosteal bone area, mineralizing surface, or bone formation rate. Rather, neurectomy spatially redistributed load-induced bone formation toward the lateral tibial surface with a reduction in periosteal bone formation at the posterolateral apex (-63%) and enhancement at the lateral surface (+1360%). Altogether, this contributed to comparable load-induced changes in cortical bone area fraction. Our results show that local skeletal innervation modulates but is not required for skeletal adaptation to applied load in our model. This supports the continued use of loading and weight-bearing exercise as an effective strategy to increase bone mass, even in settings of peripheral nerve damage or dysfunction.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 3","pages":"ziaf006"},"PeriodicalIF":3.4,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557085","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
Dental manifestations of hypophosphatasia: translational and clinical advances. 低磷血症的牙齿表现:转化和临床进展。
IF 3.4
JBMR Plus Pub Date : 2025-01-06 eCollection Date: 2025-02-01 DOI: 10.1093/jbmrpl/ziae180
Elis J Lira Dos Santos, Fatma F Mohamed, Kaitrin Kramer, Brian L Foster
{"title":"Dental manifestations of hypophosphatasia: translational and clinical advances.","authors":"Elis J Lira Dos Santos, Fatma F Mohamed, Kaitrin Kramer, Brian L Foster","doi":"10.1093/jbmrpl/ziae180","DOIUrl":"10.1093/jbmrpl/ziae180","url":null,"abstract":"<p><p>Hypophosphatasia (HPP) is an inherited error in metabolism resulting from loss-of-function variants in the <i>ALPL</i> gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP plays a crucial role in biomineralization of bones and teeth, in part by reducing levels of inorganic pyrophosphate (PP<sub>i</sub>), an inhibitor of biomineralization. HPP onset in childhood contributes to rickets, including growth plate defects and impaired growth. In adulthood, osteomalacia from HPP contributes to increased fracture risk. HPP also affects oral health. The dentoalveolar complex, that is, the tooth and supporting connective tissues of the surrounding periodontia, include 4 unique hard tissues: enamel, dentin, cementum, and alveolar bone, and all can be affected by HPP. Premature tooth loss of fully rooted teeth is pathognomonic for HPP. Patients with HPP often have complex oral health issues that require multidisciplinary dental care, potentially involving general or pediatric dentists, periodontists, prosthodontists, and orthodontists. The scientific literature to date has relatively few reports on dental care of individuals with HPP. Animal models to study HPP included global <i>Alpl</i> knockout mice, <i>Alpl</i> mutation knock-in mice, and mice with tissue-specific conditional <i>Alpl</i> ablation, allowing for new studies on pathological mechanisms and treatment effects in dental and skeletal tissues. Enzyme replacement therapy (ERT) in the form of injected, recombinant mineralized tissue-targeted TNAP has been available for nearly a decade and changed the prognosis for those with HPP. However, effects of ERT on dental tissues remain poorly defined and limitations of the current ERT have prompted exploration of gene therapy approaches to treat HPP. Preclinical gene therapy studies are promising and may contribute to improved oral health in HPP.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 2","pages":"ziae180"},"PeriodicalIF":3.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052406","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
Load-to-strength ratio as an estimate of wrist facture after gastric bypass vs gastric banding. 负荷-强度比作为胃旁路与胃束带术后腕关节骨折的估计。
IF 3.4
JBMR Plus Pub Date : 2024-12-30 eCollection Date: 2025-03-01 DOI: 10.1093/jbmrpl/ziae175
Grace H Jung, Bita Zahedi, Mary L Bouxsein, Elaine W Yu
{"title":"Load-to-strength ratio as an estimate of wrist facture after gastric bypass vs gastric banding.","authors":"Grace H Jung, Bita Zahedi, Mary L Bouxsein, Elaine W Yu","doi":"10.1093/jbmrpl/ziae175","DOIUrl":"10.1093/jbmrpl/ziae175","url":null,"abstract":"<p><p>Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) lead to long-term deficits in bone density but are also accompanied by decreased weight, which may lower the impact force with falls. The aim of this study was to compare the long-term skeletal impact of RYGB and AGB using a biomechanical evaluation of load-to-strength ratio at the distal radius as a surrogate for wrist fracture risk. We conducted a cross-sectional study evaluating bone microarchitectural parameters and bone turnover in adults who received either RYGB or AGB surgery ≥10 yr ago (RYGB: <i>n</i> = 22; AGB: <i>n</i> = 23). Bone strength at the distal radius was estimated by microfinite element analysis from HR-pQCT. We used a single-spring biomechanical model to estimate impact force and then calculated load-to-strength ratio as a ratio of impact force to bone strength, with higher load-to-strength ratios representing a higher susceptibility to fracture. In multivariable analyses, the RYGB group had higher bone resorption marker C-telopeptide (CTX) levels, lower volumetric bone density, and worse cortical and trabecular microarchitectural parameters than the AGB group. Furthermore, estimated bone strength at the radius was lower in the RYGB group (3725 ± 139 N vs 4141 ± 157 N, <i>p</i> = .030), and the load-to-strength ratio was higher in RYGB group as compared with AGB (0.84 ± 0.04 vs 0.72 ± 0.05, <i>p</i> = .035), suggestive of higher propensity for wrist fracture. Taken together, these results indicate the long-term deleterious skeletal effects are more concerning with RYGB than AGB.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 3","pages":"ziae175"},"PeriodicalIF":3.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189301","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
Understanding the structural biology of osteomalacia through multiscale 3D X-ray and electron tomographic imaging: a review of X-linked hypophosphatemia, the Hyp mouse model, and imaging methods. 通过多尺度三维x射线和电子断层成像了解骨软化症的结构生物学:x连锁低磷血症、Hyp小鼠模型和成像方法的综述。
IF 3.4
JBMR Plus Pub Date : 2024-12-30 eCollection Date: 2025-02-01 DOI: 10.1093/jbmrpl/ziae176
Daniel J Buss, Joseph Deering, Natalie Reznikov, Marc D McKee
{"title":"Understanding the structural biology of osteomalacia through multiscale 3D X-ray and electron tomographic imaging: a review of X-linked hypophosphatemia, the <i>Hyp</i> mouse model, and imaging methods.","authors":"Daniel J Buss, Joseph Deering, Natalie Reznikov, Marc D McKee","doi":"10.1093/jbmrpl/ziae176","DOIUrl":"10.1093/jbmrpl/ziae176","url":null,"abstract":"<p><p>Biomineralization in bones and teeth is a highly regulated extracellular event. In the skeleton, mineralization at the tissue level is controlled within the collagenous extracellular matrix by both circulating and local factors. While systemic regulation of mineral ion homeostasis has been well-studied over many decades, much less is known about the regulation of mineralization at the local level directly within the extracellular matrix. Some local regulators have been identified, such as tissue-nonspecific alkaline phosphatase (TNAP), phosphate-regulating endopeptidase homolog X-linked (PHEX), pyrophosphate, and osteopontin, and others are currently under investigation. Dysregulation of the actions of enzyme-inhibitor substrate pairs engaged in mineralization (as we describe by the <i>Stenciling Principle</i> for extracellular matrix mineralization) leads to osteomalacic \"soft bone\" diseases, such as hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). This review addresses how advances in 3D imaging tools and software now allow contextual and correlative viewing and interpretation of mineralized tissue structure across most length scales. Contextualized and integrated 3D multiscale data obtained from these imaging modalities have afforded an unprecedented structural biology view of bone from the macroscale to the nanoscale. Such correlated volume imaging data is highly quantitative, providing not only an integrated view of the skeleton in health, but also a means to observe alterations that occur in disease. In the context of the many hierarchical levels of skeletal organization, here we summarize structural features of bone over multiple length scales, with a focus on nano- and microscale features as viewed by X-ray and electron tomography imaging methods (submicron μCT and FIB-SEM). We additionally summarize structural changes observed after dysregulation of the mineralization pathway, focusing here on the <i>Hyp</i> mouse model for XLH. More specifically, we summarize how mineral patterns/packs at the microscale (3D crossfibrillar mineral tessellation), and how this is defective in <i>Hyp</i> mouse bone and <i>Hyp</i> enthesis fibrocartilage.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 2","pages":"ziae176"},"PeriodicalIF":3.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079752","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
A protein corona modulates the function of mineralization-competent matrix vesicles. 蛋白质电晕调节矿化能力的基质囊泡的功能。
IF 3.4
JBMR Plus Pub Date : 2024-12-24 eCollection Date: 2025-02-01 DOI: 10.1093/jbmrpl/ziae168
Juçara Gastaldi Cominal, Heitor Gobbi Sebinelli, Larwsk Hayann, Lucas Fabrício Bahia Nogueira, Marcos Antonio Eufrásio Cruz, Maryanne Trafanni Mello, Luiz Henrique da Silva Andrilli, Maytê Bolean, Ana Paula Ramos, Saida Mebarek, Massimo Bottini, José Luis Millán, Pietro Ciancaglini
{"title":"A protein corona modulates the function of mineralization-competent matrix vesicles.","authors":"Juçara Gastaldi Cominal, Heitor Gobbi Sebinelli, Larwsk Hayann, Lucas Fabrício Bahia Nogueira, Marcos Antonio Eufrásio Cruz, Maryanne Trafanni Mello, Luiz Henrique da Silva Andrilli, Maytê Bolean, Ana Paula Ramos, Saida Mebarek, Massimo Bottini, José Luis Millán, Pietro Ciancaglini","doi":"10.1093/jbmrpl/ziae168","DOIUrl":"10.1093/jbmrpl/ziae168","url":null,"abstract":"<p><p>Mineralizing cells release a special class of extracellular vesicles known as matrix vesicles (MV), crucial for bone mineralization. Following their release, MV anchor to the extracellular matrix (ECM), where their highly specialized enzymatic machinery facilitates the formation of seed mineral within the MV's lumen, subsequently releasing it onto the ECM. However, how MV propagate mineral onto the collagenous ECM remains unclear. In this study, we address these questions by exploring the \"protein corona\" paradigm whereby nanoparticles entering a biological milieu become cloaked by a corona of soluble proteins modifying their biological functions. We isolated native MV from the growth plates of chicken embryos. After removing the protein corona from the native MV using high ionic strength buffer, we obtained shaved MV. Reconstituted MVs were produced by incubating shaved MV with the removed protein corona constituents. Our results show that both the removal and reconstitution of protein corona significantly affect the biochemical and physicochemical properties of MV, resulting in 3 well-defined groups. Shaved MV exhibited an increase in tissue nonspecific alkaline phosphatase (TNAP) activity and a decrease in mineral deposition compared to native MV. Reconstituted MV partially recovered these functions, showing a reduction of TNAP activity and mineral deposition compared to native MV. Furthermore, changes in the protein corona affect the MV ability to anchor to the collagenous ECM, which is crucial for initiating the propagation of the mineral phase within this organic matrix. Proteomic analyses revealed changes in the protein profile of the MV resulting from the removal of the protein corona, indicating that shaved proteins were primarily related to external structural and ECM organization and catabolism. These findings underscore the role of the protein corona in modulating the mineralization capabilities of MV. Understanding these interactions could lead to new therapeutic strategies for enhancing bone repair and regeneration.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 2","pages":"ziae168"},"PeriodicalIF":3.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058878","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
A deep intronic PHEX variant associated with X-linked hypophosphatemia in a Finnish family. 芬兰一个家庭中与x连锁低磷血症相关的深内含子PHEX变异
IF 3.4
JBMR Plus Pub Date : 2024-12-23 eCollection Date: 2025-02-01 DOI: 10.1093/jbmrpl/ziae169
Laura Koponen, Minna Pekkinen, Jelmer Legebeke, Mari Muurinen, Salla Rusanen, Shabir Hussain, Fan Wang, Pasi I Nevalainen, Outi Mäkitie
{"title":"A deep intronic <i>PHEX</i> variant associated with X-linked hypophosphatemia in a Finnish family.","authors":"Laura Koponen, Minna Pekkinen, Jelmer Legebeke, Mari Muurinen, Salla Rusanen, Shabir Hussain, Fan Wang, Pasi I Nevalainen, Outi Mäkitie","doi":"10.1093/jbmrpl/ziae169","DOIUrl":"10.1093/jbmrpl/ziae169","url":null,"abstract":"<p><p>Hypophosphatemic rickets is a rare bone disease characterized by short stature, bone deformities, impaired bone mineralization, and dental problems. Most commonly, hypophosphatemic rickets is caused by pathogenic variants in the X-chromosomal <i>PHEX</i> gene, but autosomal dominant and recessive forms also exist. We investigated a Finnish family in which the son (index, 29 yr) and mother (56 yr) had hypophosphatemia since childhood. Both patients had typical clinical, radiographic, and biochemical features of hypophosphatemic rickets, including a pathological fracture in the son. Gene panels and whole-exome sequencing did not reveal any pathogenic variants in the known hypophosphatemia genes. Therefore, we performed whole genome sequencing and identified a deep intronic variant (c.2147 + 1197A > G) in <i>PHEX</i>. Both the affected individuals, but none of the unaffected family members, had the same variant, as confirmed by Sanger sequencing. According to RT-PCR, whole transcriptomic data, and in silico analyses, the variant led to a new splice donor site in intron 21 and an 84 basepair pseudoexon between exons 21 and 22, likely leading to the synthesis of abnormal PHEX protein. Our study underscores the importance of intronic <i>PHEX</i> variants in X-linked hypophosphatemia (XLH). In patients with features of XLH but negative gene panel or whole-exome sequencing results, the combination of whole-genome sequencing and whole transcriptomics should be considered to detect possible deep intronic variants. The methodologies presented have the potential to be used more widely in other rare diseases.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 2","pages":"ziae169"},"PeriodicalIF":3.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058877","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
Cardiovascular outcomes of romosozumab treatment-real-world data analysis. 罗莫索单抗治疗的心血管效果真实世界数据分析。
IF 3.4
JBMR Plus Pub Date : 2024-12-10 eCollection Date: 2025-01-01 DOI: 10.1093/jbmrpl/ziae146
Anat Tsur, Avivit Cahn, Ludmila Levy, Rena Pollack
{"title":"Cardiovascular outcomes of romosozumab treatment-real-world data analysis.","authors":"Anat Tsur, Avivit Cahn, Ludmila Levy, Rena Pollack","doi":"10.1093/jbmrpl/ziae146","DOIUrl":"10.1093/jbmrpl/ziae146","url":null,"abstract":"<p><p>Romosozumab is a potent treatment for osteoporosis, with significant effects on bone density and fracture prevention. This study evaluated the cardiovascular safety of romosozumab in a real-world cohort of postmenopausal women at high fracture risk. We retrospectively evaluated postmenopausal women who initiated treatment with romosozumab between January 1, 2020, and June 30, 2023. We examined the occurrence of a major adverse cardiovascular event (MACE) across two distinct segments during the treatment period and after its conclusion. After applying inclusion and exclusion criteria, 847 women were followed for a median of 729 days (IQR: 445-1060). The incidence rate of MACE was 24.0 (95% CI 17.7-32.5) per 1000 person-years during the study period. The change in the rate of MACE from 0-90 days and 90-365 days post-treatment initiation was 0.04 and 0.06 events per 1000 days, respectively. The difference in the rate between these intervals was not statistically significant (<i>p</i> = .09). After 1 yr of treatment, the slope of MACE increased to 0.10, differing significantly from the preceding 12 mo on treatment (<i>p</i><.001). The incidence of MACE was higher in those with a background of previous cardiovascular disease or diabetes at all timepoints, as expected. The consistency in event rates during treatment suggests that romosozumab is not associated with an increase in MACE in postmenopausal women. This finding challenges reports suggesting an increase in cardiovascular events within the first year of romosozumab treatment.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 1","pages":"ziae146"},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836424","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
Discoidin Domain Receptor 1 impacts bone microarchitecture with aging in female mice. 盘状蛋白结构域受体1在雌性小鼠衰老过程中影响骨微结构。
IF 3.4
JBMR Plus Pub Date : 2024-12-10 eCollection Date: 2025-02-01 DOI: 10.1093/jbmrpl/ziae160
Kimberly Denman, Angela Blissett, Stevan Glisic, Brent Weiss, Christina Zachariadou, Hani Awad, Alan Litsky, James Cray, Beth S Lee, Brian L Foster, Gunjan Agarwal
{"title":"Discoidin Domain Receptor 1 impacts bone microarchitecture with aging in female mice.","authors":"Kimberly Denman, Angela Blissett, Stevan Glisic, Brent Weiss, Christina Zachariadou, Hani Awad, Alan Litsky, James Cray, Beth S Lee, Brian L Foster, Gunjan Agarwal","doi":"10.1093/jbmrpl/ziae160","DOIUrl":"10.1093/jbmrpl/ziae160","url":null,"abstract":"<p><p>Discoidin Domain Receptor 1 (DDR1) is a receptor tyrosine kinase that binds to and is activated by collagen(s), including collagen type I. <i>Ddr1</i> deletion in osteoblasts and chondrocytes has previously demonstrated the importance of this receptor in bone development. In this study, we examined the effect of DDR1 ablation on bone architecture and mechanics as a function of aging. Femurs were collected from female global <i>Ddr1</i> knockout (KO) and wild-type (WT) mice at 2, 6, and 12 mo of age and analyzed by high-resolution micro-computed tomography (μCT), mechanical testing, and histology. Primary monocytes were collected for in vitro osteoclastogenesis assays. Our studies on younger (2 mo) mice revealed no significant differences between the two genotypes and the microarchitectural and mechanical features had a similar trend as those reported earlier for osteoblast or chondrocyte specific <i>Ddr1</i> knockdown. At an advanced age (12 mo), significant differences were noted across the two genotypes. μCT analysis showed a decrease in medullary cavity area as well as increased trabeculation in cortical and trabecular bone in the <i>Ddr1</i> KO vs. WT mice. In addition, <i>Ddr1</i> KO mouse bones exhibited reduced mechanical properties (lower peak load, yield load, and energy to yield) at 12 mo. Histological analysis revealed reduced osteoclast count in <i>Ddr1</i> KO femurs at 12 mo with no significant difference in osteocyte count between the genotypes. In vitro, osteoclastogenesis was impaired in <i>Ddr1</i> KO bone marrow derived cells. These results suggest that DDR1 deficiency adversely impacts osteoclast differentiation and bone remodeling in an age-dependent manner.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 2","pages":"ziae160"},"PeriodicalIF":3.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949040","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
Management of multiple vertebral fractures during lactation in a patient with osteogenesis imperfecta type I following twin delivery. 1例双胎分娩后成骨不全I型患者哺乳期多发椎体骨折的处理。
IF 3.4
JBMR Plus Pub Date : 2024-12-05 eCollection Date: 2025-01-01 DOI: 10.1093/jbmrpl/ziae134
Chrislyn Ng, Anne Trinh Ng, Roger Zebaze, Cat Shore-Lorenti Zebaze, Peter R Ebeling, Frances Milat
{"title":"Management of multiple vertebral fractures during lactation in a patient with osteogenesis imperfecta type I following twin delivery.","authors":"Chrislyn Ng, Anne Trinh Ng, Roger Zebaze, Cat Shore-Lorenti Zebaze, Peter R Ebeling, Frances Milat","doi":"10.1093/jbmrpl/ziae134","DOIUrl":"10.1093/jbmrpl/ziae134","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is an uncommon bone disorder caused by mutations in type I collagen involved in bone matrix leading to increased fracture risk. There are several sub-categories within OI, with OI type I being the most common and mildest form. Women with OI considering pregnancy need to be aware of bone loss and fracture risk, particularly with lactation. We report the first case of a female with twin pregnancy and OI type I who presented with multiple vertebral fractures following delivery and postpartum lactation. Following endocrine review, she weaned breast-feeding but represented within weeks with further pain and magnetic resonance imaging (MRI) demonstrating new T12 and L1 fractures. Even after receiving intravenous zoledronic acid, she experienced further thoracic pain after lifting, and MRI demonstrated a further T7 fracture. Following modification of her treatment regimen to daily teriparatide injections for 12 months, repeat dual-energy X-ray absorptiometry scan showed a significant improvement in bone mineral density at the lumbar spine and left hip. Bone loss with lactation is an important consideration for women with OI considering pregnancy. Women with OI should be assessed by an endocrinologist prior to conception to optimize bone health and have an individualized plan to mitigate bone loss and fracture risk during pregnancy and the postpartum period.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 1","pages":"ziae134"},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813100","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
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