Whole Bone Mechanics and Bone Quality

Background  

The skeleton plays a critical structural role in bearing functional loads, and failure to do so results in fracture. As we evaluate new therapeutics and consider treatments to prevent skeletal fractures, understanding the basic mechanics underlying whole bone testing and the key principles and characteristics contributing to the structural strength of a bone is critical.     

Bone Development: Overview of Bone Cells and Signaling

Vertebrates evolved elaborating a structure made up of more than 200 bones and cartilages articulated with one another to form the skeleton, through which locomotion, organ protection, lodging of hematopoiesis, and mineral homeostasis are allowed. Skeletogenesis starts at the fetal stage, along with marrow hematopoiesis, and evolves postnatally through modeling and remodeling processes that permit skeletal mass buildup. Preservation of skeletal mass is then implemented by balanced remodeling, which ensures continuous renovation of the tissue to allow its mechanical, structural, and metabolic properties to remain unaltered until ageing or diseases disrupt this equilibrium. Skeletal homeostasis is fulfilled by specialized bone cells in association with systemic and local regulators. Herein I review landmark discoveries that shed light on the intricate mesh connecting bone cells among themselves and with other systems, thus representing the cellular basis of normal and abnormal bone development and homeostasis.     

The Penetration of Lincomycin into Normal Human Bone: Determinations of Penetration into Compact Bone, Spongy Bone and Bone Marrow

The penetration of lincomycin into normal bone was studied in 10 patients with fracture of the neck of the femur, a separate determination being made of the lincomycin concentration in serum, bone marrow, spongy bone and compact bone. The concentration of lincomycin in bone marrow was found to be at the same level as that in the serum. The concentration in spongy bone amounted in most cases to 50 to 75 per cent of the concentration in the serum, whereas the concentration in compact bone varied from 0 to 15 per cent of that in the serum.     

椎间盘镜下异体松质骨复合自体红骨髓植骨治疗骨不连及骨缺损

目的探讨椎间盘镜下异体松质骨复合自体红骨髓植骨治疗四肢长骨干骨不连及骨缺损的临床疗效。方法2003年9月～2006年9月,选择25例创伤后骨不连、骨缺损患者,其中胫骨9例,股骨13例,肱骨3例。骨不连、骨缺损引起须植骨长度1～6 cm,平均2.7 cm,均在椎间盘镜下行瘢痕清除,然后在骨缺损部位植入异体松质骨,再于髂骨取自体红骨髓15～20 ml注入植骨处。结果25例随访12～36个月,平均25个月,切口均一期愈合,无一例发生神经血管损伤症状。除2例术后内固定失败外,余23例骨不连、骨缺损均获骨性愈合,植骨生长良好,骨愈合时间4～9个月,平均5.1月,无感染及再出现骨不连。结论椎间盘镜下异体松质骨复合自体红骨髓植骨治疗骨不连和骨缺损,无须自体髂骨取骨,局部创伤小,血运破坏小,并发症少,骨愈合率高,是一种微创有效的治疗方法。     

外固定架及重组合异种骨植骨治疗胫骨骨缺损与骨不连

目的：探讨外固定架和重组合异种骨(RBX)植骨治疗胫骨骨缺损、伴肢体短缩的胫骨骨不连及先天性胫骨假关节的临床疗效。方法：应用外固定架共治疗胫骨骨缺损、伴肢体短缩性骨不连及先天性胫骨假关节20例。胫骨断端清理后短缩长度2—9cm，平均4．8cm。断端应用RBX植骨12例。结果：20例病人随访8个月-7年，平均4年3个月，患肢功能恢复满意。12例应用RBX植骨治疗骨不连的平均愈合时间4．8个月。结论：本手术方法治疗胫骨骨缺损、伴肢体短缩的胫骨骨不连及先天性胫骨假关节，创伤小、操作简单，肢体功能恢复满意；RBX植骨治疗骨不连，安全，对促进骨愈合疗效可靠。     

Biomechanics of Bone: Determinants of Skeletal Fragility and Bone Quality

Bone fragility can be defined by biomechanical parameters, including ultimate force (a measure of strength), ultimate displacement (reciprocal of brittleness) and work to failure (energy absorption). Bone fragility is influenced by bone size, shape, architecture and tissue ‘quality’. Many osteoporosis treatments build bone mass but also change tissue quality. Antiresorptive therapies, such as bisphosphonates, substantially reduce bone turnover, impairing microdamage repair and causing increased bone mineralization, which can increase the brittleness of bone. Anabolic therapies, such as parathyroid hormone (PTH-(1–84)) or teriparatide (PTH-(1–34)), increase bone turnover and porosity, which offset some of the positive effects on bone strength. Osteoporosis therapies may also affect bone architecture by causing the redistribution of bone structure. Restructuring of bone during treatment may change bone fragility, even in the absence of drug effects on bone mineral density (BMD). This effect may explain why some drugs can affect fracture incidence disproportionately to changes in BMD. For instance, in a recent clinical trial, PTH-(1–34) therapy caused a dose-related increase in spinal BMD without any dose-dependent effect on the observed decrease in spinal fracture incidence. This apparent disassociation between spinal BMD and bone fragility is probably due to effects of PTH-(1–34) on bone architecture within vertebral bodies. While it has been shown that BMD is highly heritable, bone mineral distribution and architecture are also under strong genetic influence. Recent findings suggest that different genes regulate trabecular and cortical structures within lumbar vertebrae, producing a wide range of bone architectural designs. These findings suggest that there is no single optimal bone architecture; instead many different architectural solutions produce adequate bone strength. Received: 14 June 2001 / Accepted: 3 September 2001     

骨基质明胶复合自体红骨髓及同种异体骨修复骨缺损

目的:评价骨基质明胶复合自体红骨髓及同种异体骨联合移植修复骨缺损的疗效。方法:76例良性骨肿瘤和瘤样病损患者,彻底刮除病灶或作肿瘤骨段切除,并对瘤壁作灭活处理,以同种异体骨作支架,周围填充骨基质明胶和自体红骨髓复合物,术后观察机体反应及骨缺损修复情况。结果:术后机体无明显免疫排斥反应,无1例发生感染,所有病例随访时间为5～16个月,X线显示新骨形成时间为术后1.5～4月,完全骨化的时间为术后5～9月,骨缺损骨性愈合74例,并获得较好的关节功能,肿瘤复发2例。结论:骨基质明胶、自体红骨髓、同种异体骨复合物能有效修复骨缺损,有广泛的临床应用前景。     

Bionic Tiger‐Bone Powder Improves Bone Microstructure and Bone Biomechanical Strength of Ovariectomized Rats

ObjectiveTo study the curative effect of bionic tiger‐bone powder on osteoporosis in ovariectomized rats and investigate its mechanism.MethodsOverall, a 120 female Wistar rats were randomly divided into Sham (sham‐operated group), ovariectomy (OVX, ovariectomized group), TB (bionic tiger‐bone powder treatment group after ovariectomy) and TB + VD groups (bionic tiger‐bone powder + vitamin D treatment group after ovariectomy). The osteoporotic rat model was established 3 months after ovariectomy, and rats were intragastrically administrated with the corresponding drugs. Serum and bone tissue samples were collected from 10 rats in each group at weeks 4, 12 and 24 after intragastric administration. The bone microstructure of L₆ vertebrae was analyzed by MicroCT, the biomechanical strength of left femurs was measured by the three‐point bending test, and serum bone metabolism markers (P1NP and CTX) were detected by ELISA. Changes in bone collagen were analyzed by Masson''s trichrome staining and hydroxyproline detection, and members of the BMP2/SMAD/RUNX2 and OPG/RANKL/RANK signal pathways were detected by immunoblotting.ResultsCompared with the OVX group, the serum level of P1NP in the TB and TB + VD groups was higher (P < 0.05), while the CTX level was lower (P < 0.05). Bone collagen fiber structures in the TB and TB + VD groups were repaired, and the collagen content was significantly higher than that in the OVX group (P < 0.05). In the TB group, BMP‐2, P‐SMAD1/5, RUNX2 and OPG levels were increased in bone tissue (P < 0.01), RANKL levels were decreased (P < 0.01), and the bone microstructure and biomechanical strength were improved.ConclusionBionic tiger‐bone powder promotes osteogenesis by activating the BMP2/SMAD/RUNX2 signaling pathway, suppresses osteoclasts by downregulating the OPG/RANK/RANKL signaling pathway, increases bone collagen content, and improves bone microstructure and bone biomechanical strength.     

骨形态发生蛋白复合同种松质骨载体修复节段性骨缺损的实验研究

目的　本实验将探讨同种松质骨作为 BMP的载体修复节段性骨缺损。方法　将 rh BMP- 2复合同种松质骨载体 (其中含 rh BMP- 2 0 .4 mg)植入兔桡骨 15 m m人工缺损处 ,以新鲜自体松质骨植入 ,单纯同种松质骨植入作为对照 ,通过放射学骨缺损修复 L ane评分 ,Nilsson骨愈合组织学评分 ,扫描电镜观察 ,比较术后 4、8、12周各组修复骨缺损的效果。结果　 rh BMP- 2复合同种骨载体组术后 4、8、12周各项评分与同期自体骨组之间无显著性差异 (P>0 .0 5 ) ,明显优于单纯同种骨组 (P<0 .0 5 )。结论　 rh BMP- 2具有高效的骨诱导能力。同种骨是一种较理想的 BMP载体 ,rh BMP- 2复合同种松质骨载体的骨修复效果与自体骨基本一致     

骨基质明胶复合自体红骨髓及同种异体骨修复骨缺损

目的：评价骨基质明胶复合自体红骨髓及同种异体骨联合移植修复骨缺损的疗效。方法：76例良性骨肿瘤和瘤样病损患者，彻底刮除病灶或作肿瘤骨段切除，并对瘤壁作灭活处理，以同种异体骨作支架，周围填充骨基质明胶和自体红骨髓复合物，术后观察机体反应及骨缺损修复情况。结果：术后机体无明显免疫排斥反应，无1例发生感染，所有病例随访时间为5-16个月，X线显示新骨形成时间为术后1.5-4月，完全骨化的时间为术后5-9月，骨缺损骨性愈合74例，并获得较好的关节功能，肿瘤复发2例。结论：骨基质明胶、自体红骨髓、同种异体骨复合物能有效恢复骨缺损，有广泛的临床应用前景。     

带血管蒂骨瓣并双骨柱植骨治疗股骨颈部骨肿瘤

目的探讨股骨颈部骨肿瘤的手术。方法报告7例股骨颈部骨肿瘤或瘤样病变,均手术治疗。旋股外侧动脉升支血管蒂髂骨瓣并双骨柱植骨6例;缝匠肌髂骨瓣并双骨柱植骨1例。结果7例病人均获得随访,最短6个月,最长32个月,所有病人病变消失,植骨成活。髋关节功能正常6例,屈髋受限<15°1例。结论该术式治疗股骨颈部骨肿瘤,具有植骨　修复快,股骨颈强度不下降,利于关节早期活动的优点。     

Obesity and Bone

Recent studies indicate that fractures in obese postmenopausal women and older men contribute significantly to the overall fracture burden. The effect of obesity is to some extent site-dependent, the risk being increased for some fractures and decreased for others, possibly related to different patterns of falling and the presence or absence of soft tissue padding. Risk factors for fracture in obese individuals appear to be similar to those in the nonobese population, although falls may be particularly important in the obese. There is some evidence that the morbidity associated with fractures in obese individuals is greater than in the nonobese; however, a recent study indicates that the mortality associated with fracture is lower in obese and overweight people than in those of normal weight. The evidence base for strategies to prevent fractures in obese individuals is weak and is an important area for future research.     

庆大霉素重组合异种骨复合体防治开放性骨折骨缺损感染的实验研究

目的 研制庆大霉素重组合异种骨复合体（ｇｅｎｔａｍｉｃｉｎ－ｒｅｃｏｎｓｔｉｕｔｅｄ ｂｏｎｅ ｘｅｎｏｇｒａｆｔ－ｃｏｍｐｏｓｉｔｅ,Ｇ－ＲＢＸ－Ｃ）,为临床防治开放性骨折骨缺损感染提供理论依据。方法 采用具有高效骨诱导及骨肟导能力的重组合民种骨作为载体,复合庆大霉素制备庆大霉素后组合异种骨复合体,并对其体内药物释放特性、异位诱导成骨能力及骨缺损修复能力进行了研究。结果 体内药物释放试验显示：Ｇ     

Ethnic and Gender Differences in Bone Mineral Density and Bone Turnover in Young Adults: Effect of Bone Size

Generally, the incidence of osteoporotic fracture is lower in black populations and in men. These effects of ethnicity and gender may result from differences in peak bone mineral density (PBMD) and bone turnover (BT), which in turn are affected by bone size. Therefore, the aims of this study were to examine the effects of ethnicity and gender on bone mineral density (BMD) and BT in young African-Caribbean and Caucasian adults, and to adjust for the effect of bone size on BMD and BT. BMD was measured at the lumbar spine, L2–L4 (LS), total body (TB) and femoral neck (FN) by dual-energy X-ray absorptiometry in 44 blacks (16 men, 28 women) and 59 whites (28 men, 31 women) ages 20–37 years. We measured serum bone-specific alkaline phosphatase (BAP) and serum osteocalcin (OC) as markers of bone formation and urinary immunoreactive free deoxypyridinoline (ifDpd) and crosslinked N-telopeptide of type I collagen (NTx) as markers of bone resorption. To adjust the data for any differences in bone size, we calculated: (a) bone mineral apparent density (BMAD), an estimated volumetric bone density which attempts to normalize BMD measurements for bone size; and (b) bone resorption markers as a ratio to total body bone mineral content (TB BMC). Two-way analysis of variance was used to compare the effects of race and gender, and to test for any interaction between these two factors. Blacks had higher BMD compared with whites at the TB (p<0.001), LS (p= 0.0001) and FN (p= 0.0005). This increase remained significant at the LS only after calculating BMAD. Men had higher BMD at all sites (except at the LS). This increase was no longer significant at the FN after calculating BMAD, and LS BMAD was actually greater in women (p<0.0001). Blacks and whites had similar concentrations of turnover markers, but men had higher bone turnover markers than women (BAP, p<0.0001; OC, p= 0.002; ifDpd, p= 0.03; NTx, p<0.0001). This increase in bone resorption markers was no longer significant after adjusting for TB BMC (except for NTx in whites). We conclude that the skeletal advantage in blacks during young adulthood is not explained by bone size. However, it seems probable that bone size effects partially explain gender differences in BMD and bone turnover. Received: 2 February 1999 / Accepted: 2 December 1999     

骨形成蛋白与骨疾患关系的研究进展

目的：了解骨形成蛋白（ＢＭＰ）与机体骨疾患者发生发展的关系。方法：综述了近五年来ＢＭ与骨疾患关系的研究进展。结果：Ｂ屿骨发育异常、遗传性骨疾病、某些骨 异位骨化等有着直接或间接的关系。结论：搞清ＢＭＰ与机体骨疾患的关系。有助于进一步了解疾病的发病机制、病程进展和预后,为选择合适的治疗方法提供指导。     

Hypovitaminosis D and Bone Mineral Metabolism and Bone Density in Hyperthyroidism

Little is known about the impact of concomitant vitamin D deficiency on bone mineral density in hyperthyroidism. Therefore, we evaluated bone mineral measures in vitamin D–deficient and sufficient patients with hyperthyroidism. Thirty newly diagnosed consecutive patients with hyperthyroidism were included. Blood samples were used for measurement of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D [25(OH) D], and parathyroid hormone (PTH). Bone mineral density (BMD) was measured at the hip, spine, and forearm. The patients were divided into vitamin D–deficient (<25 nmol/L) and vitamin D–sufficient groups (≥25 nmol/L). Eight (26.6%) patients had 25(OH) D levels less than 25 nmol/L, with mean ± standard deviation (SD) level of 16.5 ± 3.2 (vitamin D–deficient group 1), and the remainder had a mean ± SD of 46.0 ± 13.5 nmol/L (vitamin D–sufficient group 2). Serum-intact PTH levels were significantly higher in group 1 compared with those in group 2 (31.2 ± 16.3 vs 18.0 ± 13.1 pg/mL; p = 0.041). In the vitamin D–deficient group, the mean BMD T-scores were in the osteoporotic range at hip and forearm (?2.65 ± 1.13 and ?3.04 ± 1.3) and in the osteopenia range at lumbar spine (?1.83 ± 1.71). However, in vitamin D–sufficient group, the mean BMD T-scores were in the osteopenia range (?1.64 ± 1.0, ?1.27 ± 1.6, and ?1.60 ± 0.7) at hip, forearm, and lumbar spine, respectively. The mean BMD Z-scores were also significantly lower in vitamin D–deficient group compared with those in vitamin D–sufficient group. Finally, BMD values (gm/cm²) at the hip and forearm were significantly lower in the vitamin D–deficient group compared with those in the vitamin D–sufficient group. In conclusion, hyperthyroid patients with concomitant vitamin D deficiency had lower BMD compared with vitamin D–sufficient patients.