Abstract： Objective To study thoracic bone remodeling and clinical effects after minimally invasive correctionfor pectus excavatum （PE） in children. Methods A retrospective review was conducted of a prospectively gathereddatabase of 74 child patients who underwent minimally invasive repair of PE at General Hospital of Beijing MilitaryDistrict between Apr. 2009 and Sept. 2010. Of the patients, 63 were males and 11 females; the age was（ 11.90±8.50）years, 11 patients ＜ 10-year-old among them. Under general anesthesia, two incisions were made at the side midaxillaryline, and the introducer created a tunnel at the trans-substernum and shaped the thoracic cavity. The bar was then insertedinto the retrosternum by video-assistant thoracoscopic monitoring. All patients were checked by chest computerizedtomography（CT） scan preoperatively and one week after operation, with three-dimensional reconstruction. The sagittalview was by means of the center line of the body of thoracic vertebrae. The distance between the sternum and the frontaledge of the body of thoracic vertebrae was measured and the return of displacement of the heart was observed. ResultsAll 74 operations were successful; there were no deaths. One bar was used for 66 patients （89.19%）, while two barswere used for the other 8 patients （10.81%）. Comparing the results of pre- with post-correction, for patients youngerthan 10 years（n=11） who had one bar placed, the inferior extremity of the manubrium and midsternum displacedforward to 3.76-22.92 mm. For 11-17 year-old patients（n=55） , anterior displacement of only the middle and lowerpart of the midsternum was 2.08-10.42 mm. There was a significant difference between the two groups in the inferiorextremity of the midsternum displaced（t=14.24, P ＜ 0.05）. For those patients with two bars, the inferior extremity ofthe manubrium and the midsternum were each displaced forward 4.19-15.03 mm at 7 d after operation. At 7 d after operation,the cardiac position in 65 patients（ 87.84%） of the all putted back by CT image. The chest shape of patients who received twobars was better than that of patients who received one bar. After 6-23 months of follow-up, it was pre-operative symptomsdisappeared in the patients, chest shape was satiation. Cardiac position in all patients was completely recovered. ConclusionThe thoracic bones of children with PE after minimally invasive repair have favorable remodeling. Older children requiregreater strength of support of the sternum during correction, but still realize a satisfactory therapeutic effect.
Objective To study the expression difference of Sclerostin in the medial and lateral subchondral bone of the varus osteoarthritic knee plateau. Methods The tibial plateau was obtained from 20 patients with varus knee osteoarthritis receiving total knee arthroplasty from March to October 2015. There were 8 males and 12 females with an average age of 67.8 years (range, 61-78 years). The mean course of osteoarthritis was 3.2 years (range, 2-5 years). Before operation, the varus angle was 12.0-25.5° (mean, 17.6°) on the X-ray film. Five cases were rated as grade III and 15 cases as grade IV according to Kellgren-Lawrance classification. Micro-CT scan was performed on the medial and lateral subchondral bone to compare the changes of bone structure; bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), structure model index (SMI), and the trabecular separation (Tb.Sp) were measured. Immunohistochemistry and real-time fluorescent quantitative PCR were used to test the expressions of Sclerostin protein and sost gene. Results Micro-CT showed that BV/TV, Tb.N, and Tb.Th significantly increased in the medial subchondral bone when compared with the lateral part (P<0.05), but SMI and Tb.Sp significantly reduced (P<0.05). Real-time fluorescent quantitative PCR detection showed that sost gene expression level in the medial subchondral bone (1.000) was significantly lower than that in the lateral part (4.157±2.790) (t=2.371,P=0.040). The percentage of Sclerostin positive cells in the lateral subchondral bone (52.00%±0.19%) was significantly higher than that in the medial subchondral bone (7.20%±0.04%) (t=5.094,P=0.005). Conclusion Sclerostin plays an important role in the subchondral bone remodeling of the varus osteoarthritic knee. And the low expression of Sclerostin may be an important factor to promote bone remodeling and aggravate knee deformity.
Bone remodeling requires an intimate cross-talk between osteoclasts and osteoblasts and is tightly coordinated with regulatory proteins that interact through complex autocrine/paracrine processes. Osteocytes, bone lining cells, osteomacs and vascular endothelial cells also regulate bone remodeling in the basic multicellular unit (BMU) via cell signaling networks of ligand-receptor complexes. In addition, through secreted and membrane-bound factors in the bone microenvironment, T and B lymphocytes mediate bone homeostasis for osteoimmunology. Osteoporosis and other bone diseases occur because multicellular communication within the BMU is disrupted. This review focuses on the roles of the cells in the BMU and the interaction between these cells and the factors involved in regulating bone remodeling at the cellular level. Understanding the process of bone remodeling and related genes could help us to lay the foundation for drug development against bone diseases.
Objective To review the regulation of microRNA-17-92 cluster on bone development, remodeling, and metabolism. Methods The related literature was reviewed. The clinical genetic phenotype, animal experiment, and cell research were illustrated so as to explore the possible regulatory mechanisms. Results MicroRNA-17-92 cluster is involved in physiological normal organs development, pathological neoplasm occurrence, and development. Recently, studies have shown that microRNA-17-92 cluster constitutes an intricate molecular signaling network with its upstream transcription factors and downstream targeting proteins, which controls bone development, remodeling, and metabolism exquisitely. Conclusion Present fundamental researches have certain understanding of the regulatory mechanisms of microRNA-17-92 cluster on bone development, remodeling, and metabolism. However, the exact mechanisms under these processes remain unknown.
ObjectiveTo investigate the effects of icariin (ICA) on serum bone turnover markers expressions and histological changes of cartilage and subchondral bone in mouse osteoarthritis (OA) model.MethodsEighty 8-week-old male C57BL/6J mouse were randomly divided into 8 groups (n=10). The OA model was established by anterior cruciate ligament transaction (ACLT). Group A: sham operation/early-stage normal saline administration; group B: sham operation/early-stage ICA administration; group C: ACLT/early-stage normal saline administration; group D: ACLT/early-stage ICA administration; group E: sham operation/late-stage normal saline administration; group F: sham operation/late-stage ICA administration; group G: ACLT/late-stage normal saline administration; group H: ACLT/late-stage ICA administration. Each animal received either ACLT or simply opening joint capsule, respectively. For groups B and D, ICA was given by gavage [10 mg/(kg·day)] on the first day after ACLT. For groups F and H, ICA was given with the same volume at 4 weeks after operation. The blood serum of the mouse was collected and prepared at 8 weeks after operation. Serum bone turnover markers and cytokines, including C-telopeptide of type I collagen (CTX), osteocalcin (OC), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β, were measured by ELISA. Tissue samples from the knee were stained by alcian blue/hematoxylin & orange G (AB/H&OG). Histological changes of cartilage and subchondral bone were observed and evaluated by Osteoarthritis Research Society International (OARSI) scoring system.ResultsComparison between each group with early-stage administration (groups A, B, C, and D): Compared with groups A and B, the levels of CTX and OC in group C were significantly reduced (P<0.05); the levels of IL-6, TNF-α, and IL-1β and OARSI score was significantly increased (P<0.05). Compared with group C, the levels of CTX and OC in group D were significantly increased (P<0.05); the level of IL-6 was significantly reduced (P<0.05); the levels of TNF-α and IL-1β were not changed (P>0.05), and OARSI score was significantly reduced (P<0.05). Histological observation showed that the tibial cartilage loss was significantly improved. Comparison between each group with late-stage administration (groups E, F, G, and H): Compared with groups E and F, the levels of CTX and OC in group G were significantly reduced (P<0.05); the levels of IL-6, TNF-α, and IL-1β and OARSI score were significantly increased (P<0.05). Compared with group G, the level of CTX in group H were increased (P<0.05); the levels of OC, IL-6, TNF-α, and IL-1β and OARSI score were not changed (P>0.05). Histological observation showed that the tibial cartilage loss had no changes after late-stage ICA administration.ConclusionICA plays protective effects on subchondral bone, hyaline, and calcified cartilage. Meanwhile, ICA can improve bone remodeling in subchondral bone of OA to some extent. The consistent changes of serum bone markers and pathological morphology suggest that early intervention of ICA on OA is more effective.
Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.
ObjectiveTo investigate the femoral bone remodeling and long-term effectiveness of total hip arthroplasty (THA) with anatomic medullary locking (AML) prosthesis.MethodsThe clinical data of 24 cases (26 hips) who were treated with THA with AML prosthesis between November 1997 and January 2003 were retrospectively analyzed. There were 12 males and 12 females with an age of 32-69 years (mean, 53.7 years). There were 5 cases (5 hips) of avascular necrosis of the femoral head, 6 cases (7 hips) of secondary osteoarthritis of the hip dysplasia, 6 cases (6 hips) of femoral neck fracture, 2 cases (2 hips) of primary osteoarthritis, 3 cases (3 hips) of revision surgery, 1 case (2 hips) of ankylosing spondylitis, 1 case (1 hip) of femoral head fracture. The patients were followed up at immediate, 6 weeks, 3 months, 6 months, 1 year, and then every year after operation for imaging evaluation (X-ray film was taken immediately after operation to evaluate the femoral isthmus compression, Engh standard was used to evaluate the biological fixation of the femoral shaft prosthesis, and Brooker method was used to evaluate the occurrence of heterotopic ossification); bone reconstruction evaluation [reconstruction of prosthesis and bone interface (type of bone reaction, Gruen zone, incidence, and occurrence time were recorded), reconstruction of bone around prosthesis (proximal femur stress shielding bone absorption was evaluated according to Engh and Bobyn methods, and bone mineral density change rate was measured)]; clinical efficacy evaluation [Harris score for efficacy, visual analogue scale (VAS) score for thigh pain].ResultsAll patients were followed up 15 years and 2 months to 20 years and 4 months, with a median of 16 years and 6 months. At immediate after operation, 24 hips (92.3%) had good femoral isthums compression, 24 hips (92.3%) had good bone ingrowth. Heterotopic ossification occurred in 2 patients with degree 1, 2 patients with degree 2, and 1 patient with degree 3 at 3-6 months after operation. Hyperplastic bone reactions were more common in Gruen 2, 3, 4, 5, 6, 10, 11, and 12 zones, mainly occurring at 6-20 months after operation, with the incidence of 3.8%-69.2%, with the highest incidence of spot welding. All absorptive bone reactions were osteolysis, which was common in Gruen 1 and 7 zones, and mainly occurred at 8 years after operation, with an incidence of 42.3%. No clear line (area) or enlarged sign of medullary cavity was observed. Twenty-one hips (80.8%) had 1 degree stress shieding, and 5 hips (19.2%) had 2 degree stress shieding. It mainly occurred at 10-24 months after operation in Gruen 1 and 7 zones. Dual energy X-ray absorptiometry showed that bone mineral density mainly decreased in Gruen 1, 2, 6, and 7 zones, mainly increased in Gruen 3, 4, and 5 zones. Bone mineral density loss progressed slowly after 2 years of operation, and it was stable in 5-8 years, but decreased rapidly in 8-9 years, and stabilized after 10 years. The Harris score increased from 51.1±6.2 before operation to 88.3±5.1 at last follow-up (t=–21.774, P=0.000). Mild thigh pain occurred in only 2 cases (7.7%) with the VAS score of 2. No aseptic loosening or revision of femoral prosthesis occurred during the follow-up.ConclusionThe application of AML prosthesis in THA has a good bone remodeling and a good long-term effectiveness.
ObjectiveTo explore the influence factors of anterior bone loss (ABL) after cervical disc arthroplasty (CDA) and effects of ABL on the clinical and radiographic outcomes.MethodsOne hundred and fifty-five patients who underwent single-level Prestige-LP CDA between January 2008 and December 2017 and met the inclusive criteria were enrolled in the study. Perioperative data of patients were collected. The Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), and the visual analogue scale (VAS) score were used for clinical outcomes evaluation. Radiographic parameters including cervical lordosis, C2-7 range of motion (ROM), disc angle, segmental ROM, and the lengths of the upper and lower endplates were assessed on the X-ray films. Device-related complications, including ABL, subsidence, radiographic adjacent segment pathology, and heterotopic ossification, were recorded. Univariate analysis was used to analyze the related factors, and logistic regression analysis was used to screen the influence factors. Patients were grouped according to whether ABL occurred after operation, and the differences in clinical and imaging evaluation parameters were compared.ResultsThere were 94 cases (60.6%) in the ABL group and 61 cases (39.4%) in the non-ABL group. Univariate analysis showed the significant differences in age, body mass index (BMI), and intraoperative blood loss between the two groups (P<0.05). However, there was no significant difference in gender, bone mineral density (T value), preoperative blood calcium level, preoperative blood phosphorus level, preoperative alkaline phosphatase level, operative segment, operative time, and follow-up time between the two groups (P>0.05). Multivariate analysis showed that the age and BMI were influence factors for ABL after CDA (P<0.05). The JOA score, NDI, and VAS score significantly improved in both groups at 3 months after operation (P<0.05), and the scores were further improved at last follow-up (P<0.05). There was no significant difference in JOA score, NDI, and VAS score between the two groups before and after operation (P>0.05). The preoperative cervical lordosis was significantly smaller in the ABL group than in the non-ABL group (t=−2.402, P=0.018). At last follow-up, the segmental ROM was significantly greater in the ABL group than in the non-ABL group (P<0.05), and the lengths of the upper and lower endplates were less in the ABL group than in the non-ABL group (P<0.05). No significant difference in the other radiographic parameters between the two groups were found (P>0.05). Prosthesis subsidence occurred in 5 cases (3.2%), including 3 cases in the ABL group and 2 cases in the non-ABL group; the difference between the two groups was not significant (P=1.000). Heterotopic ossification occurred in 67 cases (43.2%), including 32 cases in the ABL group and 35 cases in the non-ABL group; the difference between the two groups was significant (χ2=8.208, P=0.004). High-grade heterotopic ossification was detected in 26 cases (13 cases in the ABL group and 13 cases in the non-ABL group). Twenty-nine cases (18.7%) had radiographic adjacent segment pathology, including 15 cases in the ABL group and 14 cases in non-ABL group; the difference between the two groups was not significant (χ2=1.190, P=0.276).ConclusionThe incidence of ABL after CDA was relatively high, which mainly occurred within 3 months after operation, and no longer progressing with stable radiographic features after the first 12 months. Age and BMI were independent influence factors for ABL. ABL does not affect the clinical outcomes but may preserve more ROM of prostheses.
Objective To review the research progress of exosomes (EXOs) derived from different cells in the treatment of osteoporosis (OP). Methods Recent relevant literature about EXOs for OP therapy was extensively reviewed. And the related mechanism and clinical application prospect of EXOs derived from different cells in OP therapy were summarized and analyzed. Results EXOs derived from various cells, including bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, osteocytes, and endothelial cells, et al, can participate in many links in the process of bone remodeling, and their mechanisms involve the regulation of proliferation and differentiation of bone-related cells, the promotion of vascular regeneration and immune regulation, and the suppression of inflammatory reactions. A variety of bioactive substances contained in EXOs are the basis of regulating the process of bone remodeling, and the combination of genetic engineering technology and EXOs-based drug delivery can further improve the therapeutic effect of OP. Conclusion EXOs derived from different cells have great therapeutic effects on OP, and have the advantages of low immunogenicity, high stability, strong targeting ability, and easy storage. EXOs has broad clinical application prospects and is expected to become a new strategy for OP treatment.