Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-20DOI: 10.1016/j.bonr.2025.101866
Peter Kannu , Aliya A. Khan , Mira Francis , Jonathan D. Adachi
{"title":"Corrigendum to “Multigenerational genetic inheritance and clinical characteristics of the rare disease hypophosphatasia in 6 families: A case series” [Bone Rep. 26 (2025) 1–6 (101857)]","authors":"Peter Kannu , Aliya A. Khan , Mira Francis , Jonathan D. Adachi","doi":"10.1016/j.bonr.2025.101866","DOIUrl":"10.1016/j.bonr.2025.101866","url":null,"abstract":"","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101866"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019188","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}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.bonr.2025.101870
Mustafa UNAL , Ramazan UNLU , Sasidhar UPPUGANTI , Jeffry S. NYMAN
{"title":"Prediction of biomechanical properties of ex vivo human femoral cortical bone using Raman spectroscopy and machine learning algorithms","authors":"Mustafa UNAL , Ramazan UNLU , Sasidhar UPPUGANTI , Jeffry S. NYMAN","doi":"10.1016/j.bonr.2025.101870","DOIUrl":"10.1016/j.bonr.2025.101870","url":null,"abstract":"<div><div>This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (<em>n</em> = 118 donors; age range 21–101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (K<sub>init</sub>) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as ν<sub>1</sub>Phosphate (PO<sub>4</sub>)/CH<sub>2</sub>-wag, ν<sub>1</sub>PO<sub>4</sub>/Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (K<sub>init</sub>) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R<sup>2</sup>) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R<sup>2</sup> of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101870"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.bonr.2025.101871
Michael A. Friedman , Yasmina Zeineddine , Olivier Tuyambaze , Wesam Elhawabri , Ahmed Al Shammary , Louis Stodieck , Virginia L. Ferguson , Henry J. Donahue
{"title":"Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice","authors":"Michael A. Friedman , Yasmina Zeineddine , Olivier Tuyambaze , Wesam Elhawabri , Ahmed Al Shammary , Louis Stodieck , Virginia L. Ferguson , Henry J. Donahue","doi":"10.1016/j.bonr.2025.101871","DOIUrl":"10.1016/j.bonr.2025.101871","url":null,"abstract":"<div><div>Spaceflight (SF) and disuse result in decreases in bone and skeletal muscle volume that increase fracture risk. Hindlimb unloading (HLU) has been widely used to model the effects of microgravity. However, the effects of SF and HLU on bone and skeletal muscle have not been directly compared during long-duration SF. We examined the effects of five weeks of SF and HLU in the femurs of female Balb/c mice. For the first time, SF and HLU were directly compared using mice of the same age, strain, sex, and duration as a mission to the ISS. We hypothesized that HLU would accurately model SF, resulting in similar bone and skeletal muscle loss. Ten-week old female Balb/c mice were assigned to baseline, vivarium control, habitat control, and SF groups (n = 10/group). A separate cohort of 10-week female Balb/c mice were placed in HLU or control (n = 10/group). Femoral cortical area increased from baseline in all groups except HLU. The magnitudes of increases were lower in the SF and HLU groups. Similar effects were seen in trabecular bone. Femoral ultimate force decreased in SF and HLU groups, compared to control groups. Gastrocnemius and quadriceps mass was lower in SF and HLU mice than in control mice. HLU resulted in greater bone loss than SF, possibly due to differences in housing conditions. HLU effectively models long-duration effects of SF on the musculoskeletal system, highlighting its utility for studying astronaut health risks and developing countermeasures.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101871"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-07-28DOI: 10.1016/j.bonr.2025.101861
Michaela Tencerova , Biagio Palmisano , Stéphanie Lucas , Camille Attané , Kaisa K. Ivaska , Léa Loisay , Yoshiko M. Ikushima , Drenka Trivanovic , Alessandro Corsi , Adriana Roque , Hongshuai Li , Friederike Behler-Janbeck , Jeroen Geurts , Mara Riminucci , Izabela Podgorski , William P. Cawthorn , Bram C.J. van der Eerden , André J. van Wijnen
{"title":"Experimental analysis of bone marrow adipose tissue and bone marrow adipocytes: An update from the bone marrow adiposity society (BMAS)","authors":"Michaela Tencerova , Biagio Palmisano , Stéphanie Lucas , Camille Attané , Kaisa K. Ivaska , Léa Loisay , Yoshiko M. Ikushima , Drenka Trivanovic , Alessandro Corsi , Adriana Roque , Hongshuai Li , Friederike Behler-Janbeck , Jeroen Geurts , Mara Riminucci , Izabela Podgorski , William P. Cawthorn , Bram C.J. van der Eerden , André J. van Wijnen","doi":"10.1016/j.bonr.2025.101861","DOIUrl":"10.1016/j.bonr.2025.101861","url":null,"abstract":"<div><div>Bone marrow adipose tissue (BMAT) is physiologically linked to bone and energy metabolism, endocrine regulation, hematopoiesis and cancer-related processes. A key challenge in the field is that methods for isolating BMAT or bone marrow adipocytes (BMAds) are variable because there are no widely adopted standardized protocols. To generate awareness of this challenge and to establish uniformity in experimental approaches requiring isolation, storage and characterization of BMAT and BMAds, the Biobanking Working Group of the international Bone Marrow Adiposity Society (BMAS) has previously recommended experimental standards. This paper provides an update on this effort and presents current state-of-the-art methods and technical considerations for isolation and characterization of BMAT and BMAds, including currently available high-throughput omics approaches. This review provides a reference point based on the consensus view of BMAS investigators to support studies on biomedical, biological, biochemical and biophysical questions associated with bone marrow adiposity.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101861"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-07-28DOI: 10.1016/j.bonr.2025.101860
Xiaoqing Lu, Jun Zhu, Bai Zheng, Junsheng Wang
{"title":"Effect of denosumab combination with proximal femoral nail antirotation surgery in elderly patients with intertrochanteric femoral fractures: A comparative study","authors":"Xiaoqing Lu, Jun Zhu, Bai Zheng, Junsheng Wang","doi":"10.1016/j.bonr.2025.101860","DOIUrl":"10.1016/j.bonr.2025.101860","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effect of denosumab combined with proximal femoral nail antirotation (PFNA) surgery in elderly patients with osteoporotic intertrochanteric femoral fractures (ITF Fx).</div></div><div><h3>Design and Setting</h3><div>This retrospective, comparative study included patients aged ≥65 years with osteoporotic ITF Fx who underwent PFNA fixation at Huai'an Second People's Hospital between July 2021 and July 2023.</div></div><div><h3>Participants</h3><div>Pain relief (visual analogue scale, VAS), hip function, bone mineral density (BMD), time to fracture healing, refracture rate, and adverse events were compared.</div></div><div><h3>Interventions</h3><div>This is a retrospective study, without the addition of any intervention measures.</div></div><div><h3>Results</h3><div>A total of 76 patients were included, with 38 patients in the denosumab + PFNA group and 38 in the PFNA group. The denosumab + PFNA group showed significantly greater improvements in pain relief (1.68 ± 0.93 vs 2.29 ± 0.97, <em>p</em> = 0.014) and BMD T-score (−1.49 ± 0.61 vs −1.98 ± 0.52, <em>p</em> = 0.006) at 12 months compared to the PFNA group. Fracture healing time was significantly shorter in the denosumab + PFNA group (12.37 ± 1.38 vs 13.63 ± 1.34 weeks, <em>p</em> < 0.001), and the refracture rate was significantly lower (2.63 % vs 21.05 %, <em>p</em> < 0.05) than that in the PFNA group. The post-treatment hip function was comparable between the denosumab + PFNA and PFNA groups. Only one case of hypocalcemia was reported in the denosumab + PFNA group (2.63 %).</div></div><div><h3>Conclusion</h3><div>Denosumab combined with PFNA surgery might have an advantage in pain relief, BMD T-score, and fracture healing, while reducing refracture risk in elderly patients with osteoporotic ITF Fx compared with PFNA surgery alone.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101860"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713413","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}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-18DOI: 10.1016/j.bonr.2025.101872
Maria Sääf , Sigridur Björnsdottir , Mathias Haarhaus , Ellen-Margrethe Hauge , Diana Atanasova , Per Magnusson
{"title":"Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease","authors":"Maria Sääf , Sigridur Björnsdottir , Mathias Haarhaus , Ellen-Margrethe Hauge , Diana Atanasova , Per Magnusson","doi":"10.1016/j.bonr.2025.101872","DOIUrl":"10.1016/j.bonr.2025.101872","url":null,"abstract":"<div><div>Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism caused by mutations in the <em>ALPL</em> gene, resulting in deficient activity of tissue-nonspecific alkaline phosphatase and impaired skeletal mineralization. Affected individuals have a higher prevalence of chronic kidney disease (CKD) than the general population. We report a woman who underwent craniosynostosis surgery in infancy and lost her deciduous teeth prematurely. From age 27, she experienced recurrent foot pain due to multiple metatarsal fractures. Low levels of total alkaline phosphatase (ALP) was noted at 39 years of age, and low activities for the three bone-specific ALP (BALP) isoforms B/I, B1 and B2. Genetic analysis revealed 2 missense variants in the <em>ALPL</em> gene (p.Glu191Lys and p.Gly456Arg) confirming HPP. At age 44, she developed bilateral hip fissures requiring right-sided total hip replacement. Treatment with the parathyroid hormone analogue teriparatide (20 μg/day) was initiated at age 50, leading to increased BALP isoform levels indicating improved mineralization, less bone pain, and no new fractures during 9 months of treatment, which was stopped due to hypercalcemia and hyperphosphatemia. She began peritoneal dialysis at age 55 and received a kidney transplant at age 58. At age 65, seven years post-transplantation, she remained free of new fractures and significant bone pain. This case illustrates the long-term natural history of HPP with progressive skeletal complications across decades, and highlights the potential of short-term teriparatide as a therapeutic option for symptom relief and improved mineralization. It also suggests that kidney transplantation may contribute to improved bone health in HPP with advanced CKD.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101872"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-06DOI: 10.1016/j.bonr.2025.101867
L.H. Sattgast , A.J. Branscum , V.A. Jimenez , N. Newman , K.A. Grant , R.T. Turner , U.T. Iwaniec
{"title":"Corrigendum to “Between-subject and within-subject variability in measures of biochemical markers of bone turnover in cynomolgus and rhesus macaques” [Bone Rep. 15(2021) 101126]","authors":"L.H. Sattgast , A.J. Branscum , V.A. Jimenez , N. Newman , K.A. Grant , R.T. Turner , U.T. Iwaniec","doi":"10.1016/j.bonr.2025.101867","DOIUrl":"10.1016/j.bonr.2025.101867","url":null,"abstract":"","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101867"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019189","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}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-08DOI: 10.1016/j.bonr.2025.101869
Orit Mazza , Chemda Gluck , Noa Menkes-Caspi , Robyn Jacob Bornstein , Hagay Amir , Michael Bahar , Amir Haim
{"title":"Inpatient rehabilitation fracture liaison service (FLS) improves outcomes for secondary prevention of hip fractures","authors":"Orit Mazza , Chemda Gluck , Noa Menkes-Caspi , Robyn Jacob Bornstein , Hagay Amir , Michael Bahar , Amir Haim","doi":"10.1016/j.bonr.2025.101869","DOIUrl":"10.1016/j.bonr.2025.101869","url":null,"abstract":"<div><h3>Background</h3><div>Secondary fracture prevention is a well-defined treatment-gap within osteoporosis management. Fracture Liaison Service (FLS) coordinates the management and treatment of patients following a fragility fracture in order to close the care gap. We aim to assess the efficacy of the FLS initiative in the management and treatment of patients following fragility hip fracture in the inpatient rehabilitation setting.</div></div><div><h3>Methods</h3><div>This is a diagnostic, retrospective cohort study using a deidentified, electronic health record database. In the extraction process, patients with fragility hip fractures were identified. Patients after major trauma or malignancy were excluded. The prevalence of initiation and adherence to anti-osteoporotic treatments, including alendronate, risedronate, zoledronate, denosumab, romosozumab, and teriparatide, was compared between the rehabilitation FLS initiative patients and patients from other hospitals without FLS.</div></div><div><h3>Results</h3><div>A total of 4,124 patients with fragility hip fractures were identified between 2017 and 2021. The FLS initiative showed significantly higher rates of treatment initiation, with 72.1 % of patients receiving pharmacological therapy following a hip fracture, compared to 45.1 % in hospitals without FLS (p < 0.001). Patients in the FLS group also demonstrated higher rates of good adherence and lower rates of poor adherence (p < 0.001). Denosumab was the most commonly prescribed anti-osteoporotic treatment within the FLS initiative.</div></div><div><h3>Conclusions</h3><div>The FLS in the inpatient rehabilitation setting was found to be highly effective in improving time to treatment initiation and adherence rates to prescribe anti-osteoporosis therapy. These findings demonstrate the role of FLS in addressing the osteoporosis treatment gap following fragility hip fracture.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101869"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone ReportsPub Date : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.bonr.2025.101873
Fatma F. Mohamed , Aonjittra Phanrungsuwan , Francisco H. Nociti Jr. , Brian L. Foster
{"title":"Partial cementocyte ablation does not reduce cellular cementum apposition in a mouse model of molar super-eruption","authors":"Fatma F. Mohamed , Aonjittra Phanrungsuwan , Francisco H. Nociti Jr. , Brian L. Foster","doi":"10.1016/j.bonr.2025.101873","DOIUrl":"10.1016/j.bonr.2025.101873","url":null,"abstract":"<div><div>Cementocytes reside in the cellular cementum of the apical tooth root and resemble bone osteocytes in their markers, lacunocanalicular network, and response to mineralization defects. However, it is unclear if cementocytes have a role in regulating cellular cementum similar to that of osteocytes in controlling bone formation and resorption. The Dmp1Cre-iDTR<sup>fl/fl</sup> (Dmp1-DTR) mouse sensitizes <em>Dmp1</em>-expressing cells, including osteocytes and cementocytes, to diphtheria toxin (DT), allowing selective ablation of cell populations. Compared to iDTR<sup>fl/fl</sup> control (CTR) mice, 1.0 μg/kg intraperitoneal DT administration at 6 and 8 weeks of age increased femur cortical bone porosity and reduced alveolar bone density in Dmp1-DTR mice, validating the model. DT administration eliminated approximately 80 % of alveolar bone osteocytes and 60 % of cementocytes in <em>Dmp1Cre</em>-iDTR<sup>fl/fl</sup> mice. Mice were subjected to the challenge of unopposed first molar super-eruption, which promotes increased cellular cementum apposition. Maxillary molars were bilaterally extracted at 7 weeks, and effects on cellular cementum accumulation in mandibular first molars were analyzed at 3 weeks post-procedure using micro-computed tomography and histology. DT-directed cementocyte ablation did not alter cellular cementum volume, density, or porosity vs. CTR mice. Immunostaining showed similar distributions between treatment groups of osteopontin (OPN), an extracellular matrix protein associated with axial tooth movement. Localization of DMP1 in cellular cementum and cementocyte networks of Dmp1-DTR mice appeared reduced compared to CTR mice. Within the limits of the study, these results suggest that cementocytes are not essential for new cellular cementum formation under challenge. Further insights into roles for cementocytes require additional in vivo approaches.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101873"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone ReportsPub Date : 2025-08-06eCollection Date: 2025-09-01DOI: 10.1016/j.bonr.2025.101865
Alyson March, Sandra H Castillo Aguirre, Roman Eliseev, Regine Choe, Danielle S W Benoit
{"title":"Long-term tissue engineered periosteum-mediated allograft healing is hindered due to persistent fibrosis and limited allograft remodeling.","authors":"Alyson March, Sandra H Castillo Aguirre, Roman Eliseev, Regine Choe, Danielle S W Benoit","doi":"10.1016/j.bonr.2025.101865","DOIUrl":"10.1016/j.bonr.2025.101865","url":null,"abstract":"<p><p>Decellularized bone allografts are used in approximately 1/3 of grafting procedures and are preferred in treating critical-size bone defects, as volumetric constraints limit autografts. However, allografts demonstrate high failure rates, with 60 % of allografts failing within 10-years post-implantation. Allograft failure is linked to poor graft integration, which directly results from lack of periosteum, which surrounds bone and is necessary for successful bone healing. Therefore, a tissue-engineered periosteum (TEP) is a promising approach to recapitulate the missing periosteum and promote allograft healing. We have systematically developed an enzymatically degradable poly(ethylene glycol) (PEG) hydrogel with encapsulated mouse mesenchymal stem cells and osteoprogenitor cells, recapitulating key periosteal paracrine signals and producing improvements in bone allograft healing. While successful TEP-mediated allograft healing has been observed, previous studies have been limited to short-term healing (up to 16-weeks), which has yet to enable the observation of TEP-modified allograft healing resolution. To this end, this study extended evaluation of allograft healing in a murine femur defect model up to 12-months post-implantation. TEP-modified allografts demonstrated improvements in key bone healing outcomes, including graft vascularization and bone callus formation, at early time points (up to 9-weeks post-implantation), but improvements in healing outcomes compared to unmodified allografts were lost after 4-months post-implantation. In addition, unmodified allografts displayed incomplete healing up to 12-months post-implantation, with significant fibrotic tissue, incomplete graft remodeling, and inferior biomechanical strength observed. Given these results, future TEP designs should support long-term healing and graft remodeling to promote resolution of TEP-mediated graft healing in a clinically relevant timeline.</p>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"101865"},"PeriodicalIF":2.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}