Intraarticular injection autologous platelet‐rich plasma and bone marrow concentrate in a goat osteoarthritis model

To evaluate the effects of intraarticular injections of autologous platelet‐rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8‐fold, monocytes by 5.6‐fold, TGF‐β1 by 7.7‐fold, and IGF‐1 by 3.6‐fold (p < 0.05), and platelets were increased in PRP by 2.9‐fold, and TGF‐β1 by 3.3‐fold (p < 0.05). From the sixth week post‐operation, saline, PRP, and BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically, delayed cartilage degeneration and higher levels of extracellular matrix (ECM) were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC group showed greater cartilage protection and less ECM loss than the PRP group (p < 0.05). In summary, this study showed that intraarticular injection of autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC‐treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2140–2146, 2018.

     

Two‐step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy

Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre‐differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre‐differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy‐two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre‐differentiated MSCs, pre‐differentiated MSCs + PL). The influence of PL, BMC, and pre‐differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6‐week follow‐up, the pre‐differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre‐differentiated MSCs for treatment of a critical‐size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318–1328, 2019.     

Low‐dose BMP‐2 and MSC dual delivery onto coral scaffold for critical‐size bone defect regeneration in sheep

Tissue‐engineered constructs (TECs) combining resorbable calcium‐based scaffolds and mesenchymal stem cells (MSCs) have the capability to regenerate large bone defects. Inconsistent results have, however, been observed, with a lack of osteoinductivity as a possible cause of failure. This study aimed to evaluate the impact of the addition of low‐dose bone morphogenetic protein‐2 (BMP‐2) to MSC‐coral‐TECs on the healing of clinically relevant segmental bone defects in sheep. Coral granules were either seeded with autologous MSCs (bone marrow‐derived) or loaded with BMP‐2. A 25‐mm‐long metatarsal bone defect was created and stabilized with a plate in 18 sheep. Defects were filled with one of the following TECs: (i) BMP (n = 5); (ii) MSC (n = 7); or (iii) MSC‐BMP (n = 6). Radiographic follow‐up was performed until animal sacrifice at 4 months. Bone formation and scaffold resorption were assessed by micro‐CT and histological analysis. Bone union with nearly complete scaffold resorption was observed in 1/5, 2/7, and 3/6 animals, when BMP‐, MSC‐, and MSC‐BMP‐TECs were implanted, respectively. The amount of newly formed bone was not statistically different between groups: 1074 mm³ [970–2478 mm³], 1155 mm³ [970–2595 mm³], and 2343 mm³ [931–3276 mm³] for BMP‐, MSC‐, and MSC‐BMP‐TECs, respectively. Increased scaffold resorption rate using BMP‐TECs was the only potential side effect observed. In conclusion, although the dual delivery of MSCs and BMP‐2 onto a coral scaffold further increased bone formation and bone union when compared to single treatment, results were non‐significant. Only 50% of the defects healed, demonstrating the need for further refinement of this strategy before clinical use. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2637–2645, 2017.

     

The early phase influence of bone marrow concentrate on metaphyseal bone healing

Bone marrow concentrate (BMC) contains high densities of progenitor cells. Therefore, in critical size defects BMC may have the potency to support bone healing. The aim of this study was to investigate the effect of BMC in combination with calcium phosphate granules (CPG) on bone defect healing in a metaphyseal long bone defect in mini-pigs. A metaphyseal critical-size bone defect at the proximal tibia of 24 mini-pigs was filled with CPG combined with BMC, CPG solely (control group) or with an autograft. Radiological and histomorphometrical evaluations after 6 weeks (42 days) showed significantly more bone formation in the BMC group in the central area of the defect zone and the cortical defect zone compared to the CPG group. At the same time the resorption rate of CPG increased significantly in the BMC group. Nevertheless, compared to the BMC group the autograft group showed a significantly higher new bone formation radiologically and histomorphometrically. In BMC the count of mononuclear cells was significantly higher compared to the bone marrow aspirate (3.5-fold). The mesenchymal progenitor cell characteristics of the cells in BMC were confirmed by flow cytometry. Cells from BMC created significantly larger colonies of alkaline phosphatase-positive colony forming units (CFU-ALP) (4.4-fold) compared to cells from bone marrow aspirate. Nevertheless, even in the BMC group complete osseous bridging was only detectable in isolated instances of the bone defects. Within the limitations of this study the BMC + CPG composite promotes bone regeneration in the early phase of bone healing significantly better than the isolated application of CPG. However, the addition of BMC does not lead to a solid fusion of the defect in the early phase of bone healing an still does not represent an equal alternative to autologous bone.     

Reduced bone loss in a murine model of postmenopausal osteoporosis lacking complement component 3

The growing field of osteoimmunology seeks to unravel the complex interdependence of the skeletal and immune systems. Notably, we and others have demonstrated that complement signaling influences the differentiation of osteoblasts and osteoclasts, the two primary cell types responsible for maintaining bone homeostasis. However, the net effect of complement on bone homeostasis in vivo was unknown. Our published in vitro mechanistic work led us to hypothesize that absence of complement component 3 (C3), a central protein in the complement activation cascade, protects against bone loss in the ovariectomy‐based model of postmenopausal osteoporosis. Indeed, we report here that, when compared to their C57BL/6J (WT) counterparts, ovariectomized C3 deficient mice experienced reduced bone loss at multiple sites and increased stiffness at the femoral neck, the latter potentially improving mechanical function. WT and B6;129S4‐C3^tm1Crr/J (C3^‐/‐) mice were either ovariectomized or sham‐operated at 6 weeks of age and euthanized at 12 weeks. MicroCT on harvested bones revealed that the trabecular bone volume fraction in the metaphyses of both the proximal tibiae and distal femora of ovariectomized C3^‐/‐ mice is significantly greater than that of their WT counterparts. Lumbar vertebrae showed significantly greater osteoid content and mineral apposition rates. Mechanical testing demonstrated significantly greater stiffness in the femoral necks of ovariectomized C3^‐/‐ mice. These results demonstrate that C3 deficiency reduces bone loss at ovariectomy and may improve mechanical properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:118–128, 2018.     

不同强度跑步运动与二甲双胍联用对2型糖尿病并发骨质疏松大鼠的骨密度、骨吸收、胰岛素敏感性的影响效果研究

目的讨论不同运动强度跑步与二甲双胍联用对2型糖尿病并发骨质疏松(diabetic osteoporosis,DOP)模型大鼠骨密度、骨吸收、胰岛素敏感性的影响效果,为在运动处方与药物处方联用方案中药物使用和运动强度的合理制定提供依据。方法对120只SD大鼠购回后进行15 d适应性饲养。选取100只大鼠建立DOP动物模型,剩余20只大鼠正常饲养。检验DOP动物模型情况,建模成功的大鼠随机分为模型对照组(DM组)、二甲双胍组(metformin,MF组)、低强度跑步+二甲双胍组(LM组)、中强度跑步+二甲双胍组(MM组)、高强度跑步+二甲双胍组(HM组),正常饲养的20只大鼠为对照组(C组)。全部大鼠进行前测,内容包括骨密度(bone mineral density,BMD)、空腹血糖浓度(fasting plasma glucose,FPG)、空腹胰岛素水平(fasting insulin,FINS)、胰岛素抵抗指数(homeostasis model assessment insulin resistance,HOMA-IR)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesteroll,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesteroll,HDL-C)、抗酒石酸盐酸性磷酸酶(tartrate resistant acid phosphatase,TRACP)、尿脱氧吡啶喏啉(deoxypyridinoline,DPD)、生物力学性能等指标。前测结束后,各组大鼠按计划进行为期12周的干预,干预结束后进行后测。结果大鼠体质量方面,在干预的第4、8、12周C组大鼠体质量显著高于DM组、LM组、MM组、HM组、MF组(P0. 05),LM组大鼠体质量显著低于DM组(P0. 05)。骨密度方面,LM组、MM组、HM组、MF组大鼠后测骨密度显著高于前测和DM组后测结果,但仍然明显低于C组(P0. 05)。在骨代谢方面,LM组、MM组、HM组、MF组大鼠后测尿羟脯氨酸、尿DPD、血浆TRACP值显著高低于前测和DM组后测结果,但仍然明显高于C组(P0. 05)。在糖代谢方面,LM组、MM组、HM组、MF组大鼠FPG、FINS后测值显著低于本组前测值、DM组和HM组后测结果,但明显高于C组(P0. 05)。在胰岛素抵抗方面,MM组、HM组、MF组大鼠HOMA-IR后测值显著高低于本组前测值、MF组和HM组后测结果,但明显高于LM和MM组(P0. 05)。在脂代谢方面,LM组、MM组、HM组、MF组大鼠甘油三酯(triglyceride,TG)、TC、LDL-C后测值显著低于本组前测值、DM组后测结果,但明显高于C组(P0. 05)。LM组TG、TC、LDL-C指标后测值显著低于HM组、MF组(P0. 05)。LM组、MM组、HM组、MF组大鼠HDL-C指标后测值显著高于本组前测值、DM组后测结果,但明显低于C组(P0. 05)。结论二甲双胍搭配跑步的干预方案能够保持大鼠体重,降低血脂、血糖,缓解胰岛素抵抗,增加骨密度,减少骨吸收。其中二甲双胍搭配中低强度跑步方案在体重控制、降低血脂血糖、缓解胰岛素抵抗方面优于二甲双胍搭配高强度跑步方案。二甲双胍搭配高强度跑步方案对于2型糖尿病并发骨质疏松大鼠骨密度改善效果与二甲双胍搭配中低强度跑步方案相比具有优势。     

Animal Model for Evaluating Bone Repair with and without Adjunctive Hyperbaric Oxygen Therapy (HBO): Comparing Dose Schedules

The effect of hyperbaric oxygen (HBO) on the healing of standardized metaphyseal defects in the cortices of rat femurs was studied. The question was whether a known total amount of HBO given twice a day (BID) would have a different effect than once a day (QD) treatments. A microvascular casting technique was developed whereby vessel ingrowth at the repair site could be monitored using scanning electron microscopy (SEM). Bone repair morphology was evaluated by light microscopy (LM) and various tissue components were quantified by histomorphometry (HM). Animals were sacrificed I, 2, 3, or 5 weeks postoperatively. SEM revealed that endosteal bone ingrowth was totally responsible for the repair of the cortical defects. Moreover, endosteal vessel ingrowth did not differ between controls and either group of HBO treated animals. LM displayed enchondral ossification in controls and BID treated animals and a pronounced osteoclastic activity in the latter group throughout the repair process. By contrast the QD treated group healed by primary ossification. Judged by the HM data, QD treatment appeared to accelerate bone repair and vessel ingrowth compared to controls, while BID treatment seemed to retard these processes.     

Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer

OBJECTIVE

To assess the effects of androgen deprivation therapy (ADT) on whole‐body and regional muscle, fat and bone mass in men with prostate cancer without metastatic bone disease.

PATIENTS AND METHODS

Seventy‐two men aged 44–88 years underwent spine, hip and whole‐body dual‐energy X‐ray absorptiometry scans at baseline and after 36 weeks of ADT. The change in whole‐body and regional lean mass (LM), fat mass (FM), and bone mineral content and density (BMD) were determined. In addition, the prostate specific antigen (PSA), serum testosterone and haemoglobin levels were measured, and the level of physical activity and fatigue assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐30.

RESULTS

The upper limb, lower limb, trunk and whole‐body LM decreased by a mean (sem ) of 5.6 (0.6)%, 3.7 (0.5)%, 1.4 (0.5)% and 2.4 (0.4)% (P < 0.01), respectively, while FM increased by 20.7 (3.3)%, 18.7 (2.7)%, 12.0 (2.5)% and 13.8 (2.3)% (P < 0.001). Hip, spine, whole‐body and upper limb BMD decreased by 1.5 (0.5)%, 3.9 (0.4)%, 2.4 (0.3)% and 1.3 (0.3%) (P < 0.001), but not lower limb BMD. Serum testosterone, PSA and haemoglobin levels decreased by 93.3 (0.4)%, 98.2 (0.5)%, and 8.8 (0.9)% (P < 0.001), respectively. In addition, physical activity levels decreased and levels of fatigue increased.

CONCLUSION

After 36 weeks of ADT there was a significant decrease in whole‐body and regional LM and bone mass, while whole‐body and regional FM increased in older men with prostate cancer. Strategies to counteract changes in soft tissue and bone mass during ADT should be formulated to minimize the risk of sarcopenia, osteoporosis and obesity.     

A time course of bone response to jump exercise in C57BL/6J mice

 Exercise, by way of mechanical loading, provides a physiological stimulus to which bone tissue adapts by increased bone formation. The mechanical stimulus due to physical activity depends on both the magnitude and the duration of the exercise. Earlier studies have demonstrated that jump training for 4 weeks produces a significant bone formation response in C57BL/6J mice. An early time point with significant increase in bone formation response would be helpful in: (1) designing genetic quantitative trait loci (QTL) studies to investigate genes regulating the bone adaptive response to mechanical stimulus; and (2) mechanistic studies to investigate early stimulus to bone tissue. Consequently, we investigated the bone structural response after 2, 3, and 4 weeks of exercise with a loading cycle of ten jumps a day. We used biochemical markers and peripheral quantitative computed tomography (pQCT) of excised femur to measure bone density, bone mineral content (BMC), and area. Four-week-old mice were separated into control (n= 6) and jump groups (n= 6), and the latter groups of mice were subjected to jump exercise of 2-week, 3-week, and 4-week duration. Data (pQCT) from a mid-diaphyseal slice were used to compare bone formation parameters between exercise and control groups, and between different time points. There was no statistically significant change in bone response after 2 weeks of jump exercise as compared with the age-matched controls. After 3 weeks of jump exercise, the periosteal circumference, which is the most efficient means of measuring adaptation to exercise, was increased by 3% (P < 0.05), and total and cortical area were increased by 6% (P < 0.05) and 11% (P < 0.01), respectively. Total bone mineral density (BMD) increased by 11% (P < 0.01). The biggest changes were observed in cortical and total BMC, with the increase in total BMC being 12% (P < 0.01). Interestingly, the increase in BMC was observed throughout the length of the femur and was not confined to the mid-diaphysis. Consistent with earlier studies, mid-femur bone mass and area remained significantly elevated in the 4-week exercise group when compared with the control group of mice. The levels of the biochemical markers osteocalcin, skeletal alkaline phosphatase, and C-telopeptide were not significantly different between the exercise and control groups, indicating the absence of any systemic response due to the exercise. We conclude that a shorter exercise regimen, of 3 weeks, induced a bone response that was greater than or equal to that of 4 weeks of jump exercise reported earlier. Received: October 1, 2001 / Accepted: January 18, 2002     

Caloric restriction leads to high marrow adiposity and low bone mass in growing mice

The effects of caloric restriction (CR) on the skeleton are well studied in adult rodents and include lower cortical bone mass but higher trabecular bone volume. Much less is known about how CR affects bone mass in young, rapidly growing animals. This is an important problem because low caloric intake during skeletal acquisition in humans, as in anorexia nervosa, is associated with low bone mass, increased fracture risk, and osteoporosis in adulthood. To explore this question, we tested the effect of caloric restriction on bone mass and microarchitecture during rapid skeletal growth in young mice. At 3 weeks of age, we weaned male C57Bl/6J mice onto 30% caloric restriction (10% kcal/fat) or normal diet (10% kcal/fat). Outcomes at 6 (n = 4/group) and 12 weeks of age (n = 8/group) included body mass, femur length, serum leptin and insulin‐like growth factor 1 (IGF‐1) values, whole‐body bone mineral density (WBBMD, g/cm²), cortical and trabecular bone architecture at the midshaft and distal femur, bone formation and cellularity, and marrow fat measurement. Compared with the normal diet, CR mice had 52% and 88% lower serum leptin and 33% and 39% lower serum IGF‐1 at 6 and 12 weeks of age (p < .05 for all). CR mice were smaller, with lower bone mineral density, trabecular, and cortical bone properties. Bone‐formation indices were lower, whereas bone‐resorption indices were higher (p < .01 for all) in CR versus normal diet mice. Despite having lower percent of body fat, bone marrow adiposity was elevated dramatically in CR versus normal diet mice (p < .05). Thus we conclude that caloric restriction in young, growing mice is associated with impaired skeletal acquisition, low leptin and IGF‐1 levels, and high marrow adiposity. These results support the hypothesis that caloric restriction during rapid skeletal growth is deleterious to cortical and trabecular bone mass and architecture, in contrast to potential skeletal benefits of CR in aging animals. © 2010 American Society for Bone and Mineral Research.     

Long‐term leisure‐time physical activity has a positive effect on bone mass gain in girls

The purpose of this 7‐year prospective longitudinal study was to examine whether the level and consistency of leisure‐time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L₂–L₄) were assessed by dual‐energy X‐ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (G_LL), consistently high (G_HH), and changed from low to high (G_LH) and from high to low (G_HL) during 7 years of follow‐up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the G_LL group, the G_HH group had higher BMC (11.7% in the TF, p < .05) and BMD at the TB (4.5%) and the TF (12.2%, all p < .05) at age 18. Those in the G_LH group also had higher a BMC at each site (8.5% to 9.4%, p < .05) and a higher BMD in the TB (5.4%) and the TF (8.9%) than that of G_LL (all p < 0.05) at the age 18. Our results suggest that long‐term leisure‐time physical activity has a positive effect on bone mass gain of multiple bone sites in girls during the transition from prepuberty to early adulthood. In addition, girls whose physical activity increases during adolescence also benefit from bone mass gain. © 2010 American Society for Bone and Mineral Research     

Skeletal effects of whole‐body vibration in adult and aged mice

Low‐amplitude, whole‐body vibration (WBV) may be anabolic for bone. Animal studies of WBV have not evaluated skeletal effects in aged animals. We exposed 75 male BALB/c mice (7 month/young‐adult; 22 month/aged) to 5 weeks of daily WBV (15 min/day, 5 day/wk; 90 Hz sine wave) at acceleration amplitudes of 0 (sham), 0.3, or 1.0 g. Whole‐body bone mineral content (BMC) increased with time in 7 month (p < 0.001) but not 22 month (p = 0.34) mice, independent of WBV (p = 0.60). In 7 month mice, lower‐leg BMC increased with time in 0.3 and 1.0 g groups (p < 0.005) but not in the sham group (p = 0.09), indicating a positive WBV effect. In 22 month mice, there were no changes with time in lower‐leg BMC (p = 0.11). WBV did not affect tibial trabecular or cortical bone structure (by µCT), dynamic indices of trabecular or cortical bone formation, trabecular osteoclast surface, or the mass of the reproductive fat pad (p > 0.05). Each of these outcomes was diminished in 7 month versus 22 month animals (p < 0.05). In summary, 5 weeks of daily exposure to low‐amplitude WBV had no skeletal effects in aged male mice. The potential of WBV to enhance bone mass in age‐related osteoporosis is not supported in this preclinical study. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:241–247, 2010     

Effects of sodium bicarbonate supplementation on axial and peripheral bone mass in rats on strenuous treadmill training exercise

We observed the effects of sodium bicarbonate supplement on bone mass in rats on strenuous treadmill training. Sixty female Wistar rats (93-days-old; mean initial weight 261 ± 16 g) were studied. One group of 15 rats was killed at the beginning of the experiments (basal control group), while another group of 15 rats was not manipulated (Exer−NaB−). Another group of 15 rats was exercised but did not receive sodium bicarbonate (Exer+NaB−), while the final group of 15 rats exercised and received sodium bicarbonate (Exer+NaB+) at a dose of 0.05 mg/kg/day, administered by esophageal catheter on exercise days. These rats were killed at the end of 11 weeks. Femoral and vertebral length, weight, and bone mineral content (BMC) and density (BMD) were measured. According to anova with the Tukey–Kramer test, femur length and weight, vertebral weight, femur BMC and BMD, vertebral BMC and BMD and the ratio between femur and vertebral BMC and final body weight, and plasma bicarbonate were lower in the basal control and Exer+NaB− groups than in the two other groups (P < 0.005–0.0001). Overall, there was a positive correlation between femur and vertebral BMC and femur BMC and length (P < 0.0001 for all). Only in the Exer+NaB− group was there a positive association between plasma bicarbonate levels and femur length (r = 0.78; P < 0.0005). Our study demonstrates the adverse effects of strenuous exercise on bone, and the usefulness of sodium bicarbonate supplements in preventing and minimized these effects. Received: May 1, 2000 / Accepted: August 11, 2000     

Engraftment of discordant xenogeneic swine bone marrow cells in immunodeficient mice

Abstract: We have recently demonstrated that swine bone marrow cells (BMC) can engraft in C.B-17 scid mice. While engraftment is enhanced by providing donor-specific porcine cytokines, the level of swine hematopoiesis declines between 3 and 6 weeks post-transplant. In the present study, the utility of several strains of immunodeficient mice as recipients of swine hematopoietic cells has been determined by comparing levels of swine bone marrow engraftment at 3 weeks after bone marrow transplant. Irradiated recipients were injected with lxlO8 swine BMC and were treated daily with porcine cytokines. The presence of swine cells in BMT recipients was detected by flow cytometry and marrow colony-forming assays. Recombination activating gene-1 (RAG-1)-deficient mice were not permissive for the engraftment of swine BMC, even with administration of increased doses of whole body irradiation, or with depleting anti-NK cell antibody. In contrast, NOD-scid mice showed improved swine BMC engraftment compared to C.B-17 scid mice. Levels of swine class I+, myeloid, and CD2+ cells in bone marrow, spleen, and peripheral blood, and the number of porcine myeloid progenitor cells was significantly higher in NOD-scid recipients than in simultaneous C.B-17 scid recipients. In addition, the sera from C.B-17 scid mice markedly inhibited the proliferation of swine BMC in vitro. A weaker inhibitory effect was also mediated by sera from RAG-1-deficient mice, but not by sera from NOD-scid mice. Together, our results indicate that multiple host elements resist xenogeneic hematopoietic engraftment and function, some of which are clearly independent of host T, B, or NK cells. Understanding the basis for the advantage of NODscid mice as recipients of discordant xenogeneic porcine BMC will help to identify these elements.     

生髓健骨胶囊对酒精性骨质疏松大鼠骨密度、骨矿含量影响的研究

目的从基因分子水平探讨酒精性骨质疏松(alcoholic osteoporosis,AOP)大鼠的发病机制,观察生髓健骨胶囊对AOP大鼠骨密度(bone mineral density,BMD)、骨矿含量(bone mineral content,BMC)表达的影响,探讨生髓健骨胶囊对AOP大鼠模型的中药防治作用机理。方法选取成年雄性(清洁级)SD大鼠120只,称体重,随机分为4组,每组各30只,用白酒灌胃法造模,同时分别给予生理盐水、碳酸钙阿法D3、生髓健骨胶囊灌胃给药。于造模8、12、16周末取材,检测股骨上端BMD、BMC指标。结果检测造模干预8、12、16周后BMD、BMC指标变化,模型组BMD、BMC与正常组比较明显降低,且差异有统计学意义(P0.01),结果表明饮酒大鼠确实存在骨量减少,BMD、BMC降低;中药干预组BMD、BMC与模型组相比显著升高(P0.01);中药干预组BMD、BMC与西药对照组相比,明显升高(P0.05)。结论通过观察生髓健骨胶囊对AOP大鼠的实验指标,证明了生髓健骨胶囊能够提高AOP大鼠骨密度,增加骨矿含量,抑制矿物质丢失,改善大鼠的骨代谢。     

The prediction of cyclic proximal humerus fracture fixation failure by various bone density measures

Fixation of osteoporotic proximal humerus fractures has remained challenging, but may be improved by careful pre‐operative planning. The aim of this study was to investigate how well the failure of locking plate fixation of osteoporotic proximal humerus fractures can be predicted by bone density measures assessed with currently available clinical imaging (realistic case) and a higher resolution and quality modality (theoretical best‐case). Various density measures were correlated to experimentally assessed number of cycles to construct failure of plated unstable low‐density proximal humerus fractures (N = 18). The influence of density evaluation technique was investigated by comparing local (peri‐implant) versus global evaluation regions; HR‐pQCT‐based versus clinical QCT‐based image data; ipsilateral versus contralateral side; and bone mineral content (BMC) versus bone mineral density (BMD). All investigated density measures were significantly correlated with the experimental cycles to failure. The best performing clinically feasible parameter was the QCT‐based BMC of the contralateral articular cap region, providing significantly better correlation (R² = 0.53) compared to a previously proposed clinical density measure (R² = 0.30). BMC had consistently, but not significantly stronger correlations with failure than BMD. The overall best results were obtained with the ipsilateral HR‐pQCT‐based local BMC (R² = 0.74) that may be used for implant optimization. Strong correlations were found between the corresponding density measures of the two CT image sources, as well as between the two sides. Future studies should investigate if BMC of the contralateral articular cap region could provide improved prediction of clinical fixation failure compared to previously proposed measures. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2250–2258, 2018.

     

Percent fat mass is inversely associated with bone mass and hip geometry in rural Chinese adolescents

This study was an attempt to examine the phenotypic, genetic, and environmental correlations between percent fat mass (PFM) and bone parameters, especially hip geometry, among 786 males and 618 females aged 13 to 21 years from a Chinese twin cohort. PFM, bone area (BA), bone mineral content (BMC), cross‐sectional area (CSA), and section modulus (SM) were obtained by dual‐energy X‐ray absorptiometry. Multiple linear regression models were used to assess the PFM‐bone relationships. A structural equation model for twin design was used to estimate genetic/environmental influences on individual phenotype and phenotypic correlations. After controlling for body weight and other pertinent covariates, we observed inverse associations between PFM and bone parameters: Compared with the lowest age‐ and gender‐specific tertile of PFM, males in the highest tertile of PFM had lower measures of whole‐body‐less‐head BA (WB‐BA), lumbar spine BA (L₂–L₄‐BA), total‐hip BA (TH‐BA), total‐hip BMC, CSA, and SM (p < .005 for all, adjusted p < .05). Similar inverse associations were observed in females for all the preceding parameters except WB‐BA and L2–L₄‐BA. These associations did not vary significantly by Tanner stages. In both genders, the estimated heritabilities were 80% to 86% for BMC, 67% to 80% for BA, 74% to 77% for CSA, and 64% for SM. Both shared genetics and environmental factors contributed to the inverse PFM‐bone correlations. We conclude that in this sample of relatively lean Chinese adolescents, at a given body weight, PFM is inversely associated with BA, BMC, and hip geometry in both genders, and such associations are attributed to both shared genetic and environmental factors. © 2010 American Society for Bone and Mineral Research     

朝藿定C联合骨髓间充质干细胞移植对糖皮质激素性骨质疏松小鼠骨密度和骨代谢的影响

目的 探讨朝藿定C联合骨髓间充质干细胞移植对糖皮质激素性骨质疏松小鼠骨密度和骨代谢的影响。方法 75只雄性C57BL/6小鼠分为空白对照组、模型组、朝藿定C组、干细胞移植组、联合组，每组各15只。空白对照组以0.1 mL生理盐水肌肉注射，其余4组以0.1mL地塞米松肌肉注射，2次/周，连续干预8周，以骨密度值确定造模成功。造模成功后7 d分别进行骨髓间充质干细胞移植和朝藿定C灌胃治疗，连续8周。测定骨密度和骨结构参数、血清骨代谢指标水平以及AKT蛋白磷酸化（p-AKT）水平。结果 与空白对照组比较，模型组体质量、骨矿物质含量（BMC）、骨矿物质密度（BMD）、组织矿物质含量（TMC）、组织矿物质密度（TMD）、骨体积分数（BV/TV）、骨小梁数量（Tb.N）、骨小梁厚度（Tb.Th）以及骨源性碱性磷酸酶（BALP）、Ⅰ型前胶原羧基端前肽（PINP）、AKT蛋白磷酸化水平显著降低，骨小梁分离度（Tb.Sp）显著增加，血清骨钙素（OCN）和抗酒石酸酸性磷酸酶（Trap）水平显著升高（P＜0.05）。与模型组比较，朝藿定C组、干细胞移植组和联合组小鼠体质量、BMC、BMD、TMC、TMD、BV/TV、Tb.N、Tb.Th显著增加，BALP、PINP、AKT蛋白磷酸化水平显著升高，Tb.Sp、血清OCN和Trap水平显著降低，且联合组上述指标改善优于其余2组（P＜0.05）。结论 朝藿定C联合骨髓间充质干细胞移植可促进糖皮质激素性骨质疏松小鼠骨形成，增加骨密度，改善骨微结构，其机制可能与提高骨代谢水平和活化PI3K/AKT通路有关。