Bone modeling in experimentally induced osteoporosis in rats

Osteoporosis was experimentally induced in rats by ovariectomy (OVX), surgical excision of the sciatic nerve (NX), unilateral cordotomy (CX) and their combined operations. Each experimental group was sacrificed 12 or 24 weeks after the operation. Microdensitometrical findings, bone weight and the amount of tetracycline absorbed into the bone were examined and were compared with the control (sham op.) in order to study the bone modeling dynamics. The rats which underwent CX combined with OVX were given 1 alpha (OH)D3 and the effects of the drug were examined in a similar manner. It was concluded that bone formation decreased in OVX, that bone formation decreased and bone resorption increased simultaneously in NX, and that both bone formation and bone resorption increased in CX. 1 alpha (OH)D3 was considered to inhibit the progression of osteoporosis.     

The contribution of bone loss to postmenopausal osteoporosis

We have addressed the relative importance of peak bone mass and subsequent rate of loss in determining postmenopausal women's bone mass in old age, by examining longitudinal measurements of radial mid-shaft bone mass on various samples of healthy white postmenopausal women. Using both the variance estimate of age-specific rates of bone loss and the population variance in bone mass, we determined that rates of loss could contribute importantly to future bone mass. However, since we found a small negative correlation between initial bone mass and rate of loss, it was necessary to estimate the effect of bone loss as the complement of the contribution of initial bone mass. We found that the influence of bone loss (relative to initial bone mass) increases as the women age, such that by about age 70, the contribution of initial bone mass and rate of loss approached equality. However, estimated rates of bone loss were not very stable over time, so it was difficult to identify long-term fast-losers. We conclude that the rate of postmenopausal bone loss is an important contributor to osteoporosis at old age, but it is difficult to identify long-term fast-losers, thereby reducing the clinical value of assessments of rates of change in bone mass early in the postmenopause.     

Mechanical behavior of the subchondral bone in the experimentally induced osteoarthritis]

In order to evaluate the role of the subchondral bone (cancellous bone) in the development and progression of the joint degeneration, osteoarthritis of the knee joint was produced experimentally in the rabbits and viscoelasticity and strength of the subchondral bone from the femoral medial condyle have been investigated along with the pathological, histological study of the joint. The viscoelastic spectrometer and the Instron type testing machine were used. As the first change after operation, osteophyte formation around the joint margin has been observed before the initiation of the degeneration of articular cartilage and there is a possibility that mechanical properties of subchondral bone such as high deformability and low elasticity to the mechanism of osteophyte formation. Subchondral bone softening with marked increase of ultimate strain and phase lag, marked decrease of compressive elastic modulus and ultimate stress precedes or occurs concurrently with the degeneration of the articular cartilage. These facts indicate the relationship between the mechanical properties of the subchondral bone and joint degeneration. Once the joint degeneration starts, degeneration continues progressively while the subchondral bone tends to become brittle. These changes may be considered as a kind of functional adaptation to the damage or denudation of articular cartilage. It is postulated that some architectural changes of the subchondral bone may provide alterations of the mechanical properties. Biomechanical roles of the subchondral bone is suggested as one of the factors in the joint degeneration.     

伊班膦酸钠对糖皮质GCs诱导骨质疏松患者骨代谢指标的影响

目的观察伊班膦酸钠对糖皮质GCs诱导骨质疏松患者骨代谢指标的影响。方法以本院2017年1月至12月期间收治的48例糖皮质GCs诱导骨质疏松患者为受试对象。随机分为对照组(24例)和观察组(24例),两组患者均给予阿法骨化醇胶囊(0.5μg/次,2次/d,共12周)治疗,试验组加用伊班膦酸钠注射液(首次2 mg,此后3 mg/月,共3个月)静脉滴注治疗。比较两组患者治疗前后血清PTH、BALP、BGP、CTX-1、tPINP等骨代谢指标差异。结果对照组和试验组患者治疗前的PTH、BALP、BGP、CTX-1、tPINP表达水平比较无差异性(P均0.05)。与治疗前比较,试验组和对照组患者治疗后的BALP、PTH表达水平显著上调,BGP、CTX-1、tPINP表达水平均显著下调(P均0.05)。与对照组治疗后比较,试验组患者治疗后的BALP、PTH表达水平上调幅度更大,BGP、CTX-1、tPINP表达水平下调幅度更大(P均0.05)。结论伊班膦酸钠治疗糖皮质GCs诱导骨质疏松患者,可显著改善患者血清PTH水平的异常表达,促进骨吸收和骨形成,这可能是伊班膦酸钠治疗糖皮质GCs诱导骨质疏松临床机制中的靶点。改善糖皮质GCs诱导骨质疏松患者生活质量和治疗预后均有重要的意义。     

The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis

BackgroundRecombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model.ResultsAt the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences.ConclusionsGroups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment.

Level of evidence

Not applicable.     

The immunosuppressive effect of experimentally induced uremia

Isogeneic BN rats were made uremic by subtotal renal resections. After different periods of uremia the possibility of an immunodeficiency was evaluated by (WF X BN) F1----BN heterotopic heart transplantations. A prolongation of transplant survival was found that was not related to the duration of uremia. In some rats the uremia was reversed by isogeneic BN----BN kidney transplantation before cardiac grafting. An immediate reversal of the immunodeficiency occurred. Thus an immunosuppressive effect by uremia can be documented, and to some extent quantitated, by heterotopic heart transplantation between rats of different isogeneic strains.     

Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh^− 120/+) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh^− 120/+ mice. We also find a much larger fibril strain/tissue strain ratio in Crh^− 120/+ mice (~ 1.5) compared to the wild-type mice (~ 0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis.     

骨胶原与骨质疏松骨密度及骨生物力学的相关性研究

目的探讨骨胶原含量在绝经后骨质疏松症的发生、发展及在骨质疏松性骨折中的作用。方法取7个月龄未交配雌性SD大鼠60只，随机分为四组，A组：对照组（sham组）；B组：切除卵巢组；C组：切除卵巢＋雌激素治疗组；D组：切除卵巢＋降钙素治疗组。除A组外，其他三组通过切除双侧卵巢法12周后制成骨质疏松模型，24周后分别行k的力学特性、右侧股骨三点弯曲试验、羟脯氨酸含量、k骨密度（BMD）测定，Masson三色染色法显示骨胶原形态。结果A、C、D组与B组在k羟脯氨酸含量、BMD、k压缩力学参数值、右侧股骨生物力学参数值、骨胶原染色含量及形态方面差异均有统计学意义（P〈0．05），而A、C、D组之间差异无统计学意义（P〉0．05）。统计学分析显示羟脯氨酸含量与BMD及骨生物力学参数值呈直线相关性。结论骨质疏松的发生与骨胶原含量下降有关。骨胶原含量的下降与BMD降低及骨生物力学改变呈相关性。应用雌激素和降钙素治疗去势后骨质疏松大鼠，不仅可以提高其BMD含量和骨生物力学性能，而且还可以提高骨胶原的含量。     

The use of calcium hydroxyapatite ceramic in bone tumour surgery

We report 60 benign bone tumours treated by resection and curettage followed by the implantation of calcium hydroxyapatite ceramic (CHA). After follow-up of six to 60 months (average 36), no patient had local recurrence of the tumour or any adverse effects from the implants. In almost all cases radiography showed that the CHA was well-incorporated into the host bone, with new bone formation in and around the CHA. Corrective remodelling of deformed bone and normal fracture healing suggested that there was normal bone turnover in the presence of the CHA. Histology of biopsies from seven patients showed bone ingrowth into the pore structure of CHA in the central zone of some defects by one year after implantation. CHA appears to be a useful substitute for bone graft in the treatment of some benign tumours.     

Subperiosteal implantation of bone morphogenetic protein adsorbed to hydroxyapatite

Bone development was induced by bone morphogenetic protein (BMP) adsorbed to hydroxyapatite (HAP) under the periosteum of rat parietal bone. The BMP was isolated by Sephacryl-S200 column chromatography after passage through a membrane filter system. The yield of the fraction with BMP activity was 20 times greater than yields obtained by conventional methods. BMP was adsorbed to HAP in vacuo. HAP alone was implanted as a control. The formation of cartilage and bone was observed seven days after the implantation of BMP-HAP, and the newly formed bone fused with the host calvaria after 28 days. In control rats, no bone formation was seen within 56 days after implantation. The BMP-HAP complex was more effective in induced periosteal bone formation than HAP only.     

How to grow bone to treat osteoporosis and mend fractures

The growing number of patients with osteoporosis in our aging population need "anabolic" drugs to stimulate bone growth, improve bone microarchitecture, and accelerate fracture healing. Potent anabolic agents such as parathyroid hormone (PTH) and some of its adenylyl cyclase-stimulating fragments are either on their way, or have just now reached the clinic. This article discusses how PTHs might stimulate bone growth. The controversial bone anabolic activities of the widely used cholesterol-lowering lipophilic statins and how they might stimulate bone growth are also probed. Also, evidence is presented for leptin, a controller of body fat stores and the ovarian cycle. It has the remarkable property of being an anabolic and antianabolic that uses a hypothalamic factor to restrain osteoblast activity but by itself stimulates osteoblasts and inhibits osteoclasts.     

Changes in bone mineral in experimentally induced rickets in the rat: Electron microprobe and chemical studies

Summary The elemental composition of trabecular bone was compared for: (a) rats made rachitic on a low phosphorus, vitamin D-deficient diet; (b) rats fed the same diet but supplemented with vitamin D; (c) normal rats fed a standard laboratory diet with normal phosphorus and vitamin D levels. Quantitative energy dispersive X-ray microanalysis was performed on mineralized bone matrix at four sites: (1) clusters of mineral crystals in osteoid; (2) bone matrix adjacent to osteoid containing mineralization clusters; (3) peri-lacunar bone matrix; and (4) deep bone matrix distant from osteocytes. Estimations were also made of serum calcium, phosphorus, and 25-hydroxy-vitamin D, and of calcium, phosphorus, and hydroxyproline in whole bone. At bone sites 2, 3, and 4, the mineral content was greater in the normal group than in the other two groups. At each site, the mineral content of the rachitic bone matrix was greater than that from the vitamin D-treated group. A normal pattern of increasing mineral content with distance into the bone from a recently mineralized border was found in the normal and vitamin D-treated groups but was notably absent in the rachitic bones. Microprobe measurements of Ca:P molar ratios in hydroxyapatite standards and in normal rat bone were approximately 1.7. In both rachitic and vitamin D-treated bones, the Ca:P molar ratio was significantly higher than that in normal bones and correlated with serum Ca:P ratios. It is suggested that the increased Ca:P ratios in the rachitic and vitamin D-treated bones may be explained by an increased carbonate deposition.     

Chondroosteogenetic response to crude bone matrix proteins bound to hydroxyapatite

For the development of a new implantable biomaterial that possesses osteogenetic ability, bone matrix morphogenetic proteins were bound to hydroxyapatite (BMP-HAP). A crude protein extract including the bone morphogenetic protein (BMP) fraction was precipitated in the pores of hydroxyapatite (HAP) inside of a dialysis sac. In tissue culture, BMP-HAP or HAP was used as substratum for rat mesenchymal muscle cell explants. The BMP-HAP and HAP controls were also implanted in the muscle pouches of mice. New cartilage and/or new bone formation was observed on the exterior surface of BMP-HAP but not of HAP controls. Implantation of this HAP into bone marrow cavities of rabbit femoral and tibial condyle produced new bone formation. The deposits extended further inside BMP-HAP than HAP pores. The pore diameters of 90-200 microns produced earlier ingrowth than into larger pore sizes. BMP-HAP should be tested for clinical application as osteogenetic biomaterial for augmentation of bone regeneration.     

The challenges of promoting osteogenesis in segmental bone defects and osteoporosis

Conventional clinical management of complex bone healing scenarios continues to result in 5–10% of fractures forming non‐unions. Additionally, the aging population and prevalence of osteoporosis‐related fractures necessitate the further exploration of novel ways to augment osteogenesis in this special population. This review focuses on the current clinical modalities available, and the ongoing clinical and pre‐clinical research to promote osteogenesis in segmental bone defects, delayed unions, and osteoporosis. In summary, animal models of fracture repair are often small animals as historically significant large animal models, like the dog, continue to gain favor as companion animals. Small rodents have well‐documented limitations in comparing to fracture repair in humans, and few similarities exist. Study design, number of studies, and availability of funding continue to limit large animal studies. Osteoinduction with rhBMP‐2 results in robust bone formation, although long‐term quality is scrutinized due to poor bone mineral quality. PTH 1‐34 is the only FDA approved osteo‐anabolic treatment to prevent osteoporotic fractures. Limited to 2 years of clinical use, PTH 1‐34 has further been plagued by dose‐related ambiguities and inconsistent results when applied to pathologic fractures in systematic human clinical studies. There is limited animal data of PTH 1‐34 applied locally to bone defects. Gene therapy continues to gain popularity among researchers to augment bone healing. Non‐integrating viral vectors and targeted apoptosis of genetically modified therapeutic cells is an ongoing area of research. Finally, progenitor cell therapies and the content variation of patient‐side treatments (e.g., PRP and BMAC) are being studied. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1559–1572, 2018.     

代谢综合征对骨质疏松所致远期骨折风险的影响

目的 采用骨折风险预测简易工具(fracture risk assessment tool, FRAX)在我国中老年男性中探讨代谢综合征对骨质疏松所致远期骨折风险的影响。方法 自2019年9月至2021年12月,总计有1 580名在郑州市第三人民医院进行常规健康体检的中老年男性纳入本研究。根据代谢综合征的诊断标准,将上述受试者分为代谢综合征组和非代谢综合征组。对所有受试者的健康体检资料进行连续采集,并完成标准化社会人口学调查问卷,受试者骨质疏松的远期骨折风险采用FRAX公式进行计算和评估(FRAX-1和FRAX-2指数)。结果 单因素Logistic回归分析显示FRAX-1和FRAX-2的升高与代谢综合征有关(OR值分别为1.387与1.474,P<0.001)。Pearson相关分析提示年龄和代谢综合征异常组分合并数目与远期骨折风险显著相关。而在多因素Logistic回归分析中,同样发现受试者的年龄与代谢综合征患病与否对FRAX-1和FRAX-2所提示的远期骨折风险升高有独立的显著影响。结论 相较于非代谢综合征患者,代谢综合征患者得出的FRAX-1和FRAX-2指数更高,且代谢...     

云克对绝经后骨质疏松骨代谢调节的作用

目的评价云克对骨代谢调节的作用。方法选择明确诊断的绝经后骨质疏松患者113例,监测云克治疗前及治疗后9个月血清骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、肿瘤坏死因子（TNF-α）、白细胞介素1（IL-1）、白细胞介素6（IL-6）、雌二醇（E2）及骨密度（BMD）的变化。结果治疗前绝经后骨质疏松患者BMD及E2明显降低（P〈0.01）。IL-1、IL-6、BALP、BGP明显升高（P〈0.01）。TNF-α高于正常对照组（P〈0.05）。治疗后9个月,IL-1、IL-6、BALP、BGP较治疗前明显下降（P〈0.01）,BMD增加（P〈0.05）,E2无明显变化。结论云克对骨生成区具有明显的导向性,进入骨组织参与骨代谢调节,具有抑制破骨细胞活性,抑制骨丢失,增加BMD的作用。