JBMR Plus最新文献

{"title":"Sex hormone deficiency in male and female mice expressing the Alzheimer's disease-associated risk-factor TREM2 R47H variant impacts the musculoskeletal system in a sex- and genotype-dependent manner.","authors":"Roquelina Pianeta, Padmini Deosthale, Natasha Sanz, Rachel Kohler, Chiebuka Okpara, Matthew Arnett, Iqra Asad, Amber Rogers, Madison Gerbig, Alyson Essex, Ziyue Liu, Joseph M Wallace, Lilian I Plotkin","doi":"10.1093/jbmrpl/ziae144","DOIUrl":"10.1093/jbmrpl/ziae144","url":null,"abstract":"<p><p>The R47H variant of the triggering receptor expressed on myeloid cells 2 (TREM2) is a risk factor for Alzheimer's disease in humans and leads to lower bone mass accrual in female but not male 12-mo-old mice. To determine whether, as with aging, gonadectomy results in sex-specific musculoskeletal effects, gonad removal or SHAM surgery was performed in 4-mo-old TREM2^R47H/+ mice and WT male and female littermates (<i>n</i> = 10-12/group), with sexes analyzed separately. Body weight was lower in males, but higher in females after gonadectomy, independently of their genotype. Gonadectomy also leads to decreased BMD in males at all sites and in the whole body (total) and spine in female mice for both genotypes. Total and femur BMD was lower in gonadectomized male mice 6-wk post-surgery, independently of the genotype. On the other hand, BMD was only lower in ovariectomized WT but not TREM2^R47H/+ mice in all sites measured at this time point. Bone formation and resorption marker levels were not affected by orchiectomy, whereas CTX was higher 3 wk after surgery and P1NP showed a tendency toward lower values at the 6-wk time point only in ovariectomized WT mice. Micro-CT analyses showed no differences resulting from gonadectomy in structural parameters in femoral cortical bone for either sex, but lower tissue mineral density in males of either genotype 6-wk post-surgery. Nevertheless, biomechanical properties were overall lower in gonadectomized males of either genotype, and only for WT ovariectomized mice. Distal femur cancellous bone structure was also affected by gonadectomy in a genotype- and sex-dependent manner, with genotype-independent changes in males, and only in WT female mice. Thus, expression of the TREM2 R47H variant minimally alters the impact of gonadectomy in the musculoskeletal system in males, whereas it partially ameliorates the consequences of ovariectomy in female mice.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 1","pages":"ziae144"},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828663","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}

{"title":"In-depth clinical characterization of intravenous iron infusion-induced hypophosphatemic osteomalacia and its resolution.","authors":"Felix N von Brackel, Jonathan Grambeck, Florian Barvencik, Michael Amling, Ralf Oheim","doi":"10.1093/jbmrpl/ziae139","DOIUrl":"10.1093/jbmrpl/ziae139","url":null,"abstract":"<p><p>Iron deficiency anemia is treated by iron supplementation. Increasing evidence has shown that the carbohydrate components in iron infusions can cause hypophosphatemia and subsequent osteomalacia due to excess intact fibroblast growth factor 23 (iFGF23). We here undertook an in-depth characterization of 13 patients with iron infusion-induced osteomalacia (IIIO). Patients were characterized (monocentric institutional practice) by means of laboratory, bone density, HR-pQCT, and virtual osteoid volume estimation. We additionally report a patient who was treated with burosumab because iron infusions had to be continued despite osteomalacia. All 13 patients received ferric carboxymaltose (FCM) infusions and presented with low phosphate levels. Stopping the FCM infusions and supportive treatment by substitution of phosphate, calcium, native, and/or active Vitamin D was the chosen therapeutic approach. Pain, mobility, and biochemical data, such as serum phosphate levels, BMD, bone microstructure, and virtual osteoid volume, were the main outcome measures. Our results indicate biochemical normalization (eg, phosphate levels pre: 0.50 mmol/L ± 0.23 mmol/L, post: 0.93 mmol/L ± 0.32 mmol/L, <i>p</i><.001) after stopping the FCM infusion and establishing supportive treatment. Additionally, pain levels on the visual analog scale (VAS) decreased (VAS_pre 7.31 ± 1.22, VAS_post 2.73 ± 1.27, <i>p</i><.0001) and areal BMD (expressed by T-score) improved significantly (T-score_pre: -1.85 ± 1.84, T-score_post: -0.91 ± 2.13, <i>p</i><.05). One patient requiring ongoing FCM infusions experienced significant additional benefits from burosumab treatment. In conclusion, our results highlight the importance of monitoring phosphate in patients treated with FCM infusions. Stopping FCM infusions is effective in addressing the excess of iFGF23 and thereby phosphate wasting. Supportive therapy enables quick recovery of the musculoskeletal system and improves pain levels in these patients.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"8 12","pages":"ziae139"},"PeriodicalIF":3.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806795","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}

{"title":"Lysine specific demethylase 1 conditional myeloid cell knockout mice have decreased osteoclast differentiation due to increased IFN-<b>β</b> gene expression.","authors":"Kristina Astleford-Hopper, Juan E Abrahante Llorens, Elizabeth W Bradley, Kim C Mansky","doi":"10.1093/jbmrpl/ziae142","DOIUrl":"10.1093/jbmrpl/ziae142","url":null,"abstract":"<p><p>Osteoclasts are large multinucleated cells that degrade bone mineral and extracellular matrix. Investigating the epigenetic mechanisms orchestrating osteoclast differentiation is key to our understanding of the pathogenesis of skeletal related diseases such as periodontitis and osteoporosis. Lysine specific demethylase 1 (LSD1/KDM1A) is a member of the histone demethylase family that mediates the removal of mono- and dimethyl groups from H3K4 and H3K9 to elicit dichotomous effects on gene expression. Prior to our study, little was known about the contributions of LSD1 to skeletal development and osteoclast differentiation. Here we show that conditional deletion of <i>Lsd1</i> within the myeloid lineage or macrophage/osteoclast precursors results in enhanced bone mass of male and female mice accompanied by diminished osteoclast size in vivo. Furthermore, <i>Lsd1</i> deletion decreased osteoclast differentiation and activity within in vitro assays. Our bulk RNA-SEQ data suggest <i>Lsd1</i> ablation in male and female mice inhibits osteoclast differentiation due to enhanced expression of interferon-β target genes. Lastly, we demonstrate that LSD1 forms an immune complex with HDAC1 and HDAC2. These data suggest that the combination of methylation and acetylation of histone residues, facilitated by LSD1, mechanistically promotes osteoclast gene expression.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 1","pages":"ziae142"},"PeriodicalIF":3.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813093","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}

{"title":"Altered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction.","authors":"Benjamin Osipov, Armaun J Emami, Hailey C Cunningham, Sophie Orr, Yu-Yang Lin, Elias H Jbeily, Ritvik S Punati, Deepa K Murugesh, Hannah M Zukowski, Gabriela G Loots, Randy Carney, Diego Vargas, Virginia L Ferguson, Blaine A Christiansen","doi":"10.1093/jbmrpl/ziae135","DOIUrl":"10.1093/jbmrpl/ziae135","url":null,"abstract":"<p><p>Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes. This causes enhanced osteoblast proliferation, followed by disruption in lacunar-canalicular connectivity and massive osteocyte death by 10 wk of age. We hypothesized that reduced viable osteocyte density would decrease the magnitude of systemic bone loss after femur fracture, reduce perilacunar remodeling, and alter callus formation. Bone remodeling was assessed using serum biomarkers of bone formation and resorption at 5 d post-fracture. We used micro-computed tomography, high resolution x-ray microscopy, mechanical testing, and Raman spectroscopy to quantify the magnitude of systemic bone loss, as well as changes in osteocyte lacunar volume, bone strength, and bone composition 2 wk post-fracture. Fracture was associated with a reduction in circulating markers of bone resorption in non-transgenic (TG-) animals. TG+ mice exhibited high bone mass in the limbs, greater cortical elastic modulus and reduced post-yield displacement. After fracture, TG+ mice lost less trabecular bone than TG- mice, but conversely TG+ mice exhibited trends toward a lower yield point and reduced femoral cortical thickness after fracture, though these were not statistically significant. Lacunar density was greater in TG+ mice, but fracture did not alter lacunar volume in TG+ or TG- mice. These findings suggest that osteocytes potentially play a significant role in the post-traumatic systemic response to fracture, though the effects differ between trabecular and cortical bone.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"8 12","pages":"ziae135"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739456","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}

{"title":"The uremic toxin indoxyl sulfate decreases osteocyte RANKL/OPG and increases Wnt inhibitor RNA expression that is reversed by PTH.","authors":"Neal X Chen, Kalisha D O'Neill, Hannah E Wilson, Shruthi Srinivasan, Lynda Bonewald, Sharon M Moe","doi":"10.1093/jbmrpl/ziae136","DOIUrl":"10.1093/jbmrpl/ziae136","url":null,"abstract":"<p><p>Renal osteodystrophy (ROD) leads to increased fractures, potentially due to underlying low bone turnover in chronic kidney disease (CKD). We hypothesized that indoxyl sulfate (IS), a circulating toxin elevated in CKD and a ligand for the aryl hydrocarbon receptor (AhR), may target the osteocytes leading to bone cell uncoupling in ROD. The IDG-SW3 osteocytes were cultured for 14 days (early) and 35 days (mature osteocytes) and incubated with 500 μM of IS after dose finding studies to confirm AhR activation. Long-term incubation of IS for 14 days led to decreased expression of Tnfsf11/Tnfrsf11b ratio (RANKL/OPG), which would increase osteoclast activity, and increased expression of Wnt inhibitors Sost and Dkk1, which would decrease bone formation in addition to decreased mineralization and alkaline phosphatase (ALP) activity. When osteocytes were incubated with IS and the AhR translocation inhibitor CH223191, mineralization and ALP activity were restored. However, the Tnfsf11/Tnfrsf11b ratio and Sost, Dkk1 expression were not altered compared with IS alone, suggesting more complex signaling. In both early and mature osteocytes, co-culture with parathyroid hormone (PTH) and IS reversed the IS-induced upregulation of Sost and Dkk1, and IS enhanced the PTH-induced increase of the Tnfsf11/Tnfrsf11b ratio. Co-culture of IS with PTH additively enhanced the AhR activity assessed by <i>Cyp1a1</i> and <i>Cyp1b1</i> expression. In summary, IS in the absence of PTH increased osteocyte messenger RNA (mRNA) Wnt inhibitor expression in both early and mature osteocytes, decreased mRNA expression ofTnfsf11/Tnfrsf11b ratio and decreased mineralization in early osteocytes. These changes would lead to decreased resorption and formation resulting in low bone remodeling. These data suggest IS may be important in the underlying low turnover bone disease observed in CKD when PTH is not elevated. In addition, when PTH is elevated, IS interacts to further increase Tnfsf11/Tnfrsf11b ratio for osteoclast activity in both early and mature osteocytes, which would worsen bone resorption.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 1","pages":"ziae136"},"PeriodicalIF":3.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813118","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}

{"title":"Therapy with transitions from one bone-forming agent to another: a retrospective cohort study on teriparatide and romosozumab.","authors":"Tomonori Kobayakawa, Yasuhide Kanayama, Yuji Hirano, Toshitaka Yukishima, Yukio Nakamura","doi":"10.1093/jbmrpl/ziae131","DOIUrl":"10.1093/jbmrpl/ziae131","url":null,"abstract":"<p><p>This study aimed to evaluate the effectiveness of sequential therapy with a bone formation-promoting agent (either teriparatide or romosozumab) for osteoporosis treatment following prior treatment with the other bone-forming agent (teriparatide or romosozumab). This is a multicenter retrospective cohort study observing 2 groups for comparison: one with 69 patients transitioning from teriparatide to romosozumab (the T2R group) and the other with 25 patients transitioning from romosozumab to teriparatide (the R2T group), monitored for 12 months on the second drug. Key outcomes included changes in bone mineral density (BMD), bone turnover marker changes, and adverse events. The mean ages of each group were 72.3 years in the T2R group and 67.6 years in the R2T group, with the proportions of women being 91.3% and 80.0%, respectively. The percent changes of BMD in the lumbar spine after 12 months of sequential therapy were +10.8% in the T2R group (<i>p</i> < .001 versus baseline) and -0.0% in the R2T group (<i>p</i> = .875). The percent changes in BMD in the total hip and femoral neck were +4.4% and +4.4% in the T2R group, and -1.3% and -0.8% in the R2T group, respectively. When comparing the 2 groups, BMD changes at all sites in the T2R group were significantly higher than those in the R2T group (<i>p</i> < .001). Furthermore, when examining the changes in the proportion of patients who achieved the osteoporosis treatment goal of a T-score exceeding -2.5, no significant increase was observed in the R2T group, whereas a significant increase was observed in the lumbar spine in the T2R group. Regarding therapy switching between bone-forming agents, this study suggests that transitioning from teriparatide to romosozumab increases BMD more effectively than transitioning in the opposite sequence.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"8 12","pages":"ziae131"},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739458","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}

{"title":"Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology, and resorptive activity.","authors":"Molly E Muehlebach, Staci L Haney, Yashpal S Chhonker, Mamunur Rashid, Daryl J Murry, Geoffrey Talmon, Sarah A Holstein","doi":"10.1093/jbmrpl/ziae133","DOIUrl":"10.1093/jbmrpl/ziae133","url":null,"abstract":"<p><p>Nitrogen bisphosphonates, such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in the isoprenoid biosynthetic pathway (IBP), and are the frontline treatment for osteolytic bone diseases. A strong affinity of these agents for bone limits their distribution out of the skeleton. Geranylgeranyl diphosphate synthase (GGDPS) is directly downstream to FDPS in the IBP and novel GGDPS inhibitors such as RAM2061 have been shown to have key drug-like features including prolonged half-life, metabolic stability, and systemic distribution. Furthermore, RAM2061 exerts anti-neoplastic benefits in mouse models of multiple myeloma and Ewing sarcoma. Therefore, we are interested in determining the potential impact of RAM2061 on osteoclast biology and bone remodeling. Studies utilizing undifferentiated RAW264.7 cells demonstrated that treatment with RAM2061 depletes cells of geranylgeranyl diphosphate, impairs protein geranylgeranylation, and induces markers of the unfolded protein response pathway and apoptosis. Differentiation of RAW264.7 cells to mature osteoclasts is disrupted by RAM2061, resulting in decreased numbers of mature osteoclasts, altered morphology, and decreased tartrate-resistant acid phosphatase activity. Treatment of fully differentiated RAW264.7 cells with RAM2061 led to decreased resorptive activity. Confocal microscopy studies revealed that RAM2061 disrupts Cdc42 localization, inhibiting proper actin ring formation in osteoclasts. No significant impact on bone turnover markers or bone histomorphology was observed following a 3-week treatment of CD-1 mice with RAM2061, although decreased numbers of osteoclasts were observed. Liquid chromatography-tandem mass spectrometry studies confirmed accumulation of RAM2061 in bone from the in vivo studies as well as hydroxyapatite binding in vitro. In conclusion, these studies are the first to demonstrate the anti-osteoclastic activity of GGDPS inhibitor treatment and support future studies exploring the therapeutic benefit of this novel therapy in the setting of pathological bone remodeling.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 1","pages":"ziae133"},"PeriodicalIF":3.4,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854205","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}

{"title":"Evaluating the relationship between glycemic control and bone fragility within the UK Biobank: observational and one-sample Mendelian randomization analyses.","authors":"Samuel Ghatan, Fjorda Koromani, Katerina Trajanoska, Evert F S van Velsen, Maryam Kavousi, M Carola Zillikens, Carolina Medina-Gomez, Ling Oei, Fernando Rivadeneira","doi":"10.1093/jbmrpl/ziae126","DOIUrl":"10.1093/jbmrpl/ziae126","url":null,"abstract":"<p><p>We aimed to: (1) examine the relationship between glycemic control, BMD estimated from heel ultrasound (eBMD) and fracture risk in individuals with type 1 (T1D) and type 2 diabetes (T2D) and (2) perform a one-sample Mendelian randomization (MR) study to explore potential causal associations between glycemic control, eBMD, and fractures. This study comprised 452 131 individuals from the UK Biobank with glycated hemoglobin A1C (HbA_1c) and eBMD levels. At baseline, 4078 participants were diagnosed with T1D and 23 682 with T2D. HbA_1c was used to classify patients into \"adequately-\" (ACD; <i>n</i> = 17 078; HbA_1c < 7.0%/53 mmol/mol) and \"inadequately-\" (ICD; <i>n</i> = 10 682; HbA_1c ≥ 7.0%/53 mmol/mol) controlled diabetes. In individuals with T1D, a 1% unit (11 mmol/mol) increase in HbA_1c levels was associated with a 12% increase in fracture risk (HR: 1.12, 95% CI [1.05-1.19]). Fracture risk was highest in individuals with T1D and ICD (HR 2.84, 95%CI [2.53, 3.19]), followed by those with ACD (HR 2.26, 95%CI [1.91, 2.69]), as compared to subjects without diabetes. Evidence for a non-linear association between HbA_1c and fracture risk was observed (F-test ANOVA <i>p</i>-value = 0.002) in individuals with T2D, with risk being increased at both low and high levels of HbA_1c. Fracture risk between the T2D ACD and ICD groups was not significantly different (HR: 0.97, 95%CI [0.91-1.16]), despite increased BMD. In MR analyses genetically predicted higher HbA_1c levels were not significantly associated with fracture risk (causal risk ratio: 1.04, 95%CI [0.95-1.14]). We did observe evidence of a non-linear causal association with eBMD (quadratic test <i>p</i>-value = 0.0002), indicating U-shaped relationship between HbA_1c and eBMD. We obtained evidence that lower HbA_1c levels will reduce fracture risk in patients with T1D. In individuals with T2D, lowering HbA_1c levels can mitigate the risk of fractures up to a threshold, beyond which the risk may begin to rise again.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"8 11","pages":"ziae126"},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521864","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}

{"title":"Correction to: Evidence for peri-lacunar remodeling and altered osteocyte lacuno-canalicular network in mouse models of myeloma-induced bone disease.","authors":"","doi":"10.1093/jbmrpl/ziae123","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae123","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/jbmrpl/ziae093.].</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"8 10","pages":"ziae123"},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346837","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}

{"title":"Healing sequelae following tooth extraction and dental implant placement in an aged, ovariectomy model.","authors":"Jessica M Latimer, Shogo Maekawa, Takahiko Shiba, Tobias Fretwurst, Michael Chen, Lena Larsson, James V Sugai, Paul Kostenuik, Bruce Mitlak, Beate Lanske, William V Giannobile","doi":"10.1093/jbmrpl/ziae113","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae113","url":null,"abstract":"<p><p>At present, a lack of consensus exists regarding the clinical impact of osteoporosis on alveolar bone metabolism during implant osseointegration. While limited preclinical and clinical evidence demonstrates a negative influence of osteoporosis on dental extraction socket healing, no preclinical studies offer data on the results of implant placement in 6-mo-old, ovariectomized (OVX) Sprague-Dawley rats. This study aimed to investigate the outcomes of dental tooth extraction socket healing and implant placement in a rodent model of osteoporosis following daily vehicle (VEH) or abaloparatide (ABL) administration. Micro-CT and histologic analysis demonstrated signs of delayed wound healing, consistent with alveolar osteitis in extraction sockets following 42 d of healing in both the VEH and ABL groups. In a semiquantitative histological analysis, the OVX-ABL group demonstrated a tendency for improved socket regeneration with a 3-fold greater rate for moderate socket healing when compared to the OVX-VEH group (43% vs 14%), however, this finding was not statistically significant (<i>p</i>=.11). No significant differences were observed between vehicle and test groups in terms of implant outcomes (BMD and bone volume/total volume) at 14- and 21-d post-implant placement. Abaloparatide (ABL) significantly increased BMD of the femoral shaft and intact maxillary alveolar bone sites in OVX animals, demonstrating the therapeutic potential for oral hard tissue regeneration. The present model involving estrogen-deficiency-induced bone loss demonstrated an impaired healing response to dental extraction and implant installation.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"8 10","pages":"ziae113"},"PeriodicalIF":3.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346839","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}