OBJECTIVE: To evaluate the 10-year influence of soft tissue height (STH) on crestal bone level changes (CBC) in bone-level implants with non-matching internal conical connections.
METHODS: From the initial 97 patients, 59 (19 men, 40 women, age 55.86 ± 9.5 years) returned for the recall visit. Based on baseline STH, they were categorized into T1 (thin STH ≤2 mm, n = 33), T2 (thin STH augmented with allogenic tissue matrix (ATM), n = 32), and C (thick STH >2mm, n = 32). Implants were placed in the posterior mandible using a one-stage approach and received single screw-retained restorations. Clinical (PPD, BOP, PI) and radiographic examinations were conducted after 10 years, with CBC calculated mesial and distal to each implant.
RESULTS: After 10 years, implants in surgically thickened (T2) or naturally thick STH (C) showed bone gains of 0.57 ± 0.55mm and 0.56 ± 0.40mm, respectively (p < 0.0001) shifting from an initial CBC of -0.21 ± 0.33 mm to 0.36 ± 0.29 mm in the thick STH group and -0.2 ± 0.35 mm to 0.37 ± 0.29 mm in the surgically thickened STH group after 10 years. Implants in naturally thin STH yielded a non-significant trend of bone loss (-0.12 ± 0.41mm; p > 0.05).
CONCLUSIONS: Implants in thin STH (≤2 mm) exhibited greater CBC over the study period. Significant bone gains were observed in thick STH cases, indicating that naturally thick STH or STH augmentation with ATM and may contribute to maintaining CBC in long-term around implants.
CONCLUSIONS: This is the first long-term follow-up study suggesting that adequate soft tissue height around implants helps maintain stable peri-implant bone levels. While tissue thickness plays a key role, other factors also interact with peri-implant tissue height to sustain crestal bone stability over time.

The bone turnover capability influences the acquisition and maintenance of osseointegration. The architectures of osteocyte three-dimensional (3D) networks determine the direction and activity of bone turnover through osteocyte intercellular crosstalk, which exchanges prostaglandins through gap junctions in response to mechanical loading. Titanium nanosurfaces with anisotropically patterned dense nanospikes promote the development of osteocyte lacunar-canalicular networks. We investigated the effects of titanium nanosurfaces on intercellular network development and regulatory capabilities of bone turnover in osteocytes under cyclic compressive loading. MLO-Y4 mouse osteocyte-like cell lines embedded in type I collagen 3D gels on titanium nanosurfaces promoted the formation of intercellular networks and gap junctions even under static culture conditions, in contrast to the poor intercellular connectivity in machined titanium surfaces. The osteocyte 3D network on the titanium nanosurfaces further enhanced gap junction formation after additional culturing under cyclic compressive loading simulating masticatory loading, beyond the degree observed on machined titanium surfaces. A prostaglandin synthesis inhibitor cancelled the dual effects of titanium nanosurfaces and cyclic compressive loading on the upregulation of gap junction-related genes in the osteocyte 3D culture. Supernatants from osteocyte monolayer culture on titanium nanosurfaces promoted osteocyte maturation and intercellular connections with gap junctions. With cyclic loading, titanium nanosurfaces induced expression of the regulatory factors of bone turnover in osteocyte 3D cultures, toward higher osteoblast activation than that observed on machined surfaces. Titanium nanosurfaces with anisotropically patterned dense nanospikes promoted intercellular 3D network development and regulatory function toward osteoblast activation in osteocytes activated by cyclic compressive loading, through intercellular crosstalk by prostaglandin.

BACKGROUND: Early-onset osteoporosis is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT). It remains unknown if physical training can improve bone formation in these patients, as the transplantation procedure may cause sustained dysregulation of the bone-forming osteoblast progenitor cells.
OBJECTIVE: We aimed to explore the effect of resistance training on bone remodeling in long-term survivors of pediatric HSCT.
METHODS: In this prospective, controlled intervention study, we included seven HSCT survivors and 15 age- and sex-matched healthy controls. The participants completed a 12-week heavy load, lower extremity resistance training intervention with three weekly sessions. We measured fasting serum levels of the bone formation marker \"N-terminal propeptide of type I procollagen\" (P1NP), and the bone resorption marker \"C-terminal telopeptide of type I collagen\" (CTX). The hypothesis was planned before data collection began. The trial was registered at Clinicaltrials.gov before including the first participant, with trial registration no. NCT04922970.
RESULTS: Resistance training led to significantly increased levels of fasting P1NP in both patients (from 57.62 to 114.99 ng/mL, p = .03) and controls (from 66.02 to 104.62 ng/mL, p < .001). No significant changes in fasting CTX levels were observed.
CONCLUSIONS: Despite previous high-dose cytotoxic therapy, long-term survivors of pediatric HSCT respond to resistance training with improvement of bone formation, comparable to that of healthy controls. This suggests that resistance training might be a promising non-pharmacological approach to prevent the early decline in bone mass, and should be considered as part of a follow-up program to counteract long-term sequela after pediatric HSCT.

UNASSIGNED: Short stem prostheses were originally designed for younger and more active patients. In recent years, they have been increasingly offered to older patients. This study evaluates the mid-to long-term survival of a short stem prosthesis and the changes in periprosthetic bone density following implantation of a cementless short hip stem in patients over 60 years of age.
UNASSIGNED: 118 patients aged over 60 received short stem prostheses. Clinical examination included Harris Hip Score (HHS) and Hip Disability and Osteoarthritis Outcome Score (HOOS). 93 patients were followed clinically for at least five years. 53 patients underwent dual-energy x-ray absorptiometry (DXA) and radiographic evaluation. Follow-up intervals were preoperative and postoperative (t0), at approximately six months (t1), at approximately two years (t2), and at approximately five years or later (t3).
UNASSIGNED: Over a mean 6.7-year observation period for all 118 patients, one stem revision occurred due to a traumatic periprosthetic stem fracture. The five-year survival rate for the endpoint survival of the Metha® stem in 95 at-risk patients is 99.2%. HHS improved significantly from t0 55.3 ± 11.5 (range 30-79) to t3 95.3 ± 8.6 (range 57-100) at a mean of 8.0 years (p < 0.001). HOOS improved significantly in each subscale (p < 0.001). Bone mineral density (BMD) was available for review in 53 patients after a mean of 7.1 years. BMD increased from t0 to t3 in region of interest (ROI) 3 (+0.4%) and ROI 6 (+2.9%) and decreased in ROI 1 (-10.3%), ROI 2 (-9.8%), ROI 4 (-5.3%), ROI 5 (-3.4%) and ROI 7 (-23.1%).
UNASSIGNED: The evaluated short stem prosthesis shows a remarkably high survival rate in elderly patients, accompanied by excellent clinical results. Load transfer measurements show a metaphyseal-diaphyseal pattern with a trend towards increased diaphyseal transfer over the period observed.

Some previous researches have demonstrated that appropriate mechanical stimulation can enhance bone formation. However, most studies have employed the strain energy density (SED) method for predicting bone remodeling, with only a few considering the potential impact of wall fluid shear stress (FSS) on this process. To bridge this gap, the current study compared the prediction of bone formation and resorption via SED and wall FSS by using fluid-solid coupling numerical simulation. Specifically, 8-week-old female Sprague-Dawley rats were subjected to stretching of the eighth caudal vertebra using a custom-made device. Based on micro-computed tomography images, a three-dimensional model integrating fluid-solid coupling was created to represent compact bone, cancellous bone, and bone marrow. The animals were grouped into control, 1 Hz, and 10 Hz categories, wherein a tensile displacement load of 1000 με was applied to the loading end. The results revealed that SED values tended to increase with elevated porosity, whereas wall FSS values decreased it. Notably, wall FSS demonstrated the higher predictive accuracy for cancellous bone resorption than SED. These findings support the notion that fluid flow within cancellous bone spaces can significantly impact bone resorption. Therefore, the findings of this study contribute to a more comprehensive understanding of the role of wall FSS in bone remodeling, providing a theoretical support for the dynamic evolution of bone structures under mechanical stimulation.

The ubiquitin (Ub)‑proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including skeletal cell differentiation and bone homeostasis. The Ub ligase E3 promotes the transfer of Ub to the target protein, especially transcription factors, to regulate the proliferation, differentiation and survival of bone cells, as well as bone formation. In turn, the deubiquitinating enzyme removes Ub from modified substrate proteins to orchestrate bone remodeling. As a result of abnormal regulation of ubiquitination, bone cell differentiation exhibits disorder and then bone homeostasis is affected, consequently leading to osteoporosis. The present review discussed the role and mechanism of UPS in bone remodeling. However, the specific mechanism of UPS in the process of bone remodeling is still not fully understood and further research is required. The study of the mechanism of action of UPS can provide new ideas and methods for the prevention and treatment of osteoporosis. In addition, the most commonly used osteoporosis drugs that target ubiquitination processes in the clinic are discussed in the current review.

A rise in bone turnover markers (BTM) after bariatric surgery predicts poor bone health years later. This study explored factors associated with BTM and changes in BTM after bariatric surgery. Inclusion criteria were subjects 18 to 65 years of age with morbid obesity undergoing bariatric surgery. All data were measured before and 6 and 12 months after surgery. The study included 104 subjects: women/men: 83/21; mean age 43.1 (SD 8.4) years; BMI: 38.8 kg/m2 (SD 3.8). Surgery with Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) was performed in 84 (81%) and 20 (19%) subjects, respectively. From before to 6-12 months after surgery, procollagen type 1 N-terminal propeptid (P1NP) increased by 45.6 µg/L (95% CI 41.5-50.0, p < 0.001), and alkaline phosphatase (ALP) by 10 U/L (95% CI 7-14, p < 0.001). The increases were significantly larger after RYGB than after SG. The APOE- Ɛ3 allele was associated with low levels of BTM and high levels of leptin. There was an unfavourable increase in BTM after bariatric surgery. SG compared to RYGB and the presence of the APOE-Ɛ3 allele were associated with less unfavourable effects. The study emphasises the importance of optimal prophylactic interventions after bariatric surgery to prevent osteoporosis.

The stiffness of an ideal fracture internal fixation implant should have a time-varying performance, so that the fracture can generate reasonable mechanical stimulation at different healing stages, and biodegradable materials meet this performance. A topology optimization design method for composite structures of fracture internal fixation implants with time-varying stiffness is proposed, considering the time-dependent degradation process of materials. Using relative density and degradation residual rate to describe the distribution and degradation state of two materials with different degradation rates and elastic modulus, a coupled mathematical model of degradation simulation mechanical analysis was established. Biomaterial composite structures were designed based on variable density method to exhibit time-varying stiffness characteristics. Taking the bone plate used for the treatment of tibial fractures as an example, a composite structure bone plate with time-varying stiffness characteristics was designed using the proposed method. The optimization results showed that material 1 with high stiffness formed a columnar support structure, while material 2 with low stiffness was distributed at the degradation boundary and inside. Using a bone remodeling simulation model, the optimized bone plates were evaluated. After 11 months of remodeling, the average elastic modulus of callus using degradable time-varying stiffness plates, titanium alloy plates, and stainless steel plates were 8 634 MPa, 8 521 MPa, and 8 412 MPa, respectively, indicating that the use of degradable time-varying stiffness plates would result in better remodeling effects on the callus.
理想的骨折内固定植入物刚度应具有随时间变化的性能，使骨折在不同愈合阶段都能产生合理的力学刺激，可降解材料可以满足这一性能。考虑到材料降解过程的时间依赖性，提出一种具有时变刚度的骨折内固定植入物复合结构拓扑优化设计方法。采用相对密度和降解残留率描述两种具有不同降解速度和弹性模量的材料分布和降解状态，建立降解模拟-力学分析耦合数学模型；基于变密度法设计双材料复合结构，使之具有时变刚度特性。以胫骨骨折治疗用的接骨板为例，采用所提出方法设计具有时变刚度特性的复合结构接骨板，优化结果显示高刚度的材料1形成柱状的支撑结构，低刚度的材料2分布在降解边界和内部。利用骨重塑模拟模型对优化后的接骨板进行评估，经过11个月重塑，使用可降解时变刚度接骨板、钛合金接骨板和不锈钢接骨板的骨痂平均弹性模量分别为8 634、8 521、8 412 MPa，表明使用可降解时变刚度接骨板可使骨痂取得更好的重塑效果。.

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

It is important for athlete and public health that we continue to develop our understanding of the effects of exercise and nutrition on bone health. Bone turnover markers (BTMs) offer an opportunity to accelerate the progression of bone research by revealing a bone response to exercise and nutrition stimuli far more rapidly than current bone imaging techniques. However, the association between short-term change in the concentration of BTMs and long-term bone health remains ambiguous. Several other limitations also complicate the translation of acute BTM data to applied practice. Importantly, several incongruencies exist between the effects of exercise and nutrition stimuli on short-term change in BTM concentration compared with long-term bone structural outcomes to similar stimuli. There are many potential explanations for these inconsistencies, including that short-term study designs fail to encompass a full remodeling cycle. The current article presents the opinion that data from relatively acute studies measuring BTMs may not be able to reliably inform applied practice aiming to optimize bone health. There are important factors to consider when interpreting or translating BTM data and these are discussed.