Properties of human trabecular bone cells from elderly women: implications for cell-based bone engraftment

Tissue-engineered bone regeneration offers new therapeutic options in the treatment of patients with fractures. Due to the changes in the hormone levels, elderly women are most affected by bone fractures and thus constitute one of the future target groups of cell-based bone therapy. For designing cell-based therapy approaches, a better understanding of individual-dependent variations in bone-derived cells of the host is required. In this study, a simple, high-yield procedure is described for the collection of cells from bone tissue of a high number of elderly women. The cultured cells display stem cell characteristics indicated by the presence of a CD13+, CD44+, CD90+, CD147+, CD14-, CD34-, CD45- and CD144- cell populations and by a stable undifferentiated phenotype as well as by the ability to proliferate extensively while retaining the potential to differentiate along the osteoblastic lineage even after 27 cell doublings. A high variability in the number of cell-forming units (CFUs) within a donor population of 34 samples, in the morphology within 50 donors, in the expression of alkaline phosphatase within 15 samples and in the responsiveness to BMP-2 was evident, but no age-related correlation could be found. In conclusion, the data indicate that individual variations in cell number, cell morphology and in the osteogenic potential of progenitor cells of the patient may be relevant for a successful treatment of bone fractures in the elderly by cell-based therapy approaches.     

Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density of the femoral neck in elderly Japanese women

The estrogen receptor alpha gene is a candidate locus for genetic influence on bone mass. The possible association between two polymorphisms in the first intron of this gene, alone or in combination, and bone mineral density at various sites was examined in participants in the National Institute for Longevity Sciences Longitudinal Study of Aging, a population-based prospective cohort study of aging and age-related diseases. The relationship of the TC ( PvuII) and AG ( XbaI) polymorphisms in the first intron of the estrogen receptor alpha gene to bone mineral density was determined in 2230 subjects (1120 men, 1110 women) and in 2238 subjects (1128 men, 1110 women), respectively, all of whom were community-dwelling individuals aged 40-79 years. Bone mineral density at the radius was measured by peripheral quantitative computed tomography and that for the lumbar spine, right femoral neck, right trochanter, right Ward's triangle, and total body was measured by dual-energy X-ray absorptiometry. Estrogen receptor alpha genotypes were determined with an automated fluorescent allele-specific DNA primer assay system. Analysis of the TC ( PvuII) polymorphism revealed that bone mineral density for the total body, femoral neck, and trochanter was significantly lower in women aged 60 years or over with the CC genotype than in those with the TT genotype, but statistical significance was not achieved after adjustment for age, body mass index, and smoking status. Analysis of the AG ( XbaI) polymorphism revealed that bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA genotype. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA or AG genotypes. Analysis of combined genotypes in women aged 60 years or over revealed that bone mineral density for the femoral neck was significantly lower in women with the CC/ GG genotype than in those with the TT/ AA or TC/ AA genotypes. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the CC/ GG genotype than in those with other genotypes. No differences in bone mineral density at the various sites were detected among TC ( PvuII), AG ( XbaI), or combined genotypes in women aged under 60 years or in men. These results suggest that the estrogen receptor alpha gene is a susceptibility locus for bone mass, especially for the femoral neck, in elderly Japanese women.     

Relationship between body composition and bone mineral content in young and elderly women

PRIMARY OBJECTIVE: To study the relationship between bone mineral content (BMC), lean tissue mass (LTM) and fat mass (FM) in a large sample of young and elderly women. RESEARCH DESIGN: Cross-sectional. METHODS AND PROCEDURES: BMC, LTM and FM were measured by dual-energy X-ray absorptiometry in 2009 free-dwelling Caucasian women aged 63 +/- 7 years (mean +/- SD; range: 37-88 years). The majority of women were postmenopausal (96%). RESULTS: LTM explained 13% more variance of BMC than FM (R(2)(adj) = 0.39 vs 0.26, p < 0.0001) but weight (Wt) explained 5% more variance of BMC than LTM (R(2)(adj) = 0.44, p < 0.0001). The prediction of BMC obtained from LTM and FM (R(2)(adj)= 0.46, p < 0.0001) was only slightly better than that obtained from Wt. After the effects of age, Wt and height (Ht) on BMC were taken into account by multiple regression, the contribution of LTM and FM to BMC was just one-fifth of that of Wt (R(2)(adj) for full models < or =0.56, p < 0.0001). After a further correction for bone area (BA), the contribution of LTM and FM to BMC was just one-tenth of that of BA and not different from that of Wt and Ht on practical grounds (R(2)(adj) for full models = 0.84, p < 0.0001). Thus, after inter-individual differences in age, Wt, Ht (and bone size) are taken into account, the relationship between body composition and BMC is substantially weakened. CONCLUSIONS: In Caucasian women, (1) LTM is a stronger predictor of BMC than FM, but (2) Wt is a better predictor of BMC than body composition for practical purposes, and (3) Wt and body composition are not able to explain more than 46% of BMC variance.     

Relationship between body composition and bone mineral content in young and elderly women

Primary objective : To study the relationship between bone mineral content (BMC), lean tissue mass (LTM) and fat mass (FM) in a large sample of young and elderly women. Research design : Cross-sectional. Methods and procedures : BMC, LTM and FM were measured by dual-energy X-ray absorptiometry in 2009 free-dwelling Caucasian women aged 63 &#45 7 years (mean &#45 SD; range: 37-88 years). The majority of women were postmenopausal (96%). Results : LTM explained 13% more variance of BMC than FM ( R 2 adj = 0.39 vs 0.26, p < 0.0001) but weight (Wt) explained 5% more variance of BMC than LTM ( R 2 adj = 0.44, p < 0.0001). The prediction of BMC obtained from LTM and FM ( R 2 adj = 0.46, p < 0.0001) was only slightly better than that obtained from Wt. After the effects of age, Wt and height (Ht) on BMC were taken into account by multiple regression, the contribution of LTM and FM to BMC was just one-fifth of that of Wt ( R 2 adj for full models &#114 0.56, p < 0.0001). After a further correction for bone area (BA), the contribution of LTM and FM to BMC was just one-tenth of that of BA and not different from that of Wt and Ht on practical grounds ( R 2 adj for full models = 0.84, p < 0.0001). Thus, after inter-individual differences in age, Wt, Ht (and bone size) are taken into account, the relationship between body composition and BMC is substantially weakened. Conclusions : In Caucasian women, (1) LTM is a stronger predictor of BMC than FM, but (2) Wt is a better predictor of BMC than body composition for practical purposes, and (3) Wt and body composition are not able to explain more than 46% of BMC variance.     

Cathepsin K predicts femoral neck bone mineral density change in nonosteoporotic peri- and early postmenopausal women

OBJECTIVE: Cathepsin K is a cysteine protease that plays an essential role in organic bone matrix degradation. The aim of our study was to seek correlation of serum cathepsin K levels and a change in bone mineral density (BMD) over a 3-year period in a population of healthy nonosteoporotic women. The secondary end points were the correlations of serum cathepsin K with cross-sectional BMD and with other serum bone turnover markers and age. DESIGN: In 43 healthy women aged 42 to 57 years, blood samples for determination of cathepsin K, osteocalcin, bone alkaline phosphatase, C-terminal cross-linking telopeptide of type I collagen, osteoprotegerin, and nuclear factor kappaB ligand were collected at the time of the first BMD measurement. BMD measurements were repeated after 3 years. RESULTS: We found a moderate negative correlation of serum cathepsin K levels with change in femoral neck BMD, but none with change in spinal BMD. There were no significant correlations between cross-sectional BMD of the spine or femoral neck and serum levels of cathepsin K. Serum levels of cathepsin K were not significantly correlated with any bone turnover markers studied or with age. CONCLUSIONS: Serum cathepsin K does not seem to represent a surrogate for bone turnover markers used at present, but it might be useful as a predictor of cortical bone loss.     

Changes with aging in the bone mineral content of the lumbar spine and femoral neck in healthy women in Hungary

The bone mineral content (BMC) of the lumbar spine and femoral neck was studied in relation to aging in healthy Hungarian women by duel photon-absorptiometric method. The data were compared with North-American and West-European values. The Hungarian values are lower than these for reported from North-America or France, but similar to the BMC values for Sweden. The observed vertebral and femoral bone loss could be well represented by cubic equations. The acceleration of bone loss seems to begin around 40 years. The rate of bone loss was similar to the published values but the decrease in bone loss in the 6th and 7th decades was more suggestive. With regard to the fracture-threshold below which the risk for non-traumatic fractures of vertebrae increases, about 60% of Hungarian women at age 50-59 and about 84% at age 60-69 are considered to be at risk. It is concluded that geographical and habitual differences might be important factors in the development and change of BMC for different populations.     

生物型与骨水泥型人工股骨头置换治疗高龄股骨颈骨折

背景：随着人工关节材料、工艺及技术的成熟和发展,人工股骨头置换治疗股骨颈骨折尤其是老年患者有移位的股骨颈骨折日渐普及。 目的：观察生物型与骨水泥型人工股骨头置换治疗合并心脏病老年性股骨颈骨折的临床疗效。 方法：选择2004年1月至2009年12月天津疗养院骨科中心收治合并心脏病的股骨颈骨折患者35例,其中合并心绞痛型冠心病16例,心肌梗死型冠心病8例,无症状冠心病8例,缺血性心肌病冠心病3例。18例采用生物型人工股骨头置换,17例采用骨水泥型人工股骨头置换。 结果与结论：35例患者除1例在术中死亡外,34例均获得随访,随访时间8-36个月,置换过程中出现3例并发症均为骨水泥型组,其中1例在手术过程中经抢救无效死亡,2例在置换过程中血压下降,呼吸困难,经过抢救后生命特征恢复正常。在随访过程中发现生物型组中2例骨质疏松较严重的患者有部分假体下沉,生物型组优良率89%(16/18),骨水泥型组优良率94%(16/17),提示对于合并严重心脏病的患者适合运用生物型人工股骨头置换,而有骨质疏松的患者适合运用骨水泥型人工股骨头置换。     

骨水泥型半髋置换治疗老年股骨颈骨折

背景：老年股骨颈骨折患者进行非骨水泥还是骨水泥人工股骨头置换是目前争论的焦点。 目的：对85岁以上股骨颈骨折行骨水泥型人工股骨头置换患者的高风险的临床问题和功能结果进行评估。 方法：32例股骨颈骨折患者进行骨水泥型双极人工股骨头置换治疗,所有患者在置换后1,3,6个月和以后每年行X射线片检查,患者平均随访2~5年。 结果与结论：患者出现内科并发症发生5例(16%),在随访期间内死亡4例(25%)。脱位发生1例(3%),患者均未出现异位骨化。平均Harris髋关节评分为84分。说明骨水泥型人工股骨头置换治疗老年股骨颈骨折效果较好,稳定安全。     

雌激素受体基因多态性与老年妇女的骨密度

背景：雌激素受体α基因多态性与骨质疏松的发生相关有一定的关系,但是对于危险基因型的研究还存在商榷余地。 目的：分析雌激素受体基因多态性与老年妇女骨密度的相关性。 方法：选择检查的老年健康妇女120例,提取全血基因组DNA,选择限制性内切酶PvuⅡ和XbaⅠ进行酶切,分析基因型的分布与频率。同时选择双能X射线骨密度仪测股骨颈、大转子及Ward三角处的骨密度值。 结果与结论：XbaⅠ酶切基因型XX 6例,Xx 78例,xx 36例;PvuⅡ酶切PP 32例,Pp 50例,pp 38例。不同基因型老年妇女的年龄、绝经年龄与体质量指数值对比差异无显著性意义(P > 0.05)。PvuⅡ酶切PP基因型妇女的大转子与ward三角处的骨密度值明显大于Pp及pp妇女(P < 0.05);而XbaⅠ酶切基因多态性在老年妇女中股骨颈、大转子与Ward三角的骨密度均无显著差异(P > 0.05)。说明雌激素受体基因多态性与老年妇女骨密度有一定的相关性,P等位基因对老年妇女大转子与Ward三角处的骨密度的维持有一定作用。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

老年女性骨密度与左心室肥厚的相关性

背景：老年女性心血管事件发生率增加与骨量减少相关,左心室肥厚是明确的心血管事件独立危险因素,这两者在发病机制上可能相关。 目的：探讨老年女性骨量与左心室质量指数的相关关系。 方法：选取老年女性受试者157例,按照骨密度分组,分为骨量正常组、骨量减少和骨质疏松组。进行病史询问及临床检查,测定生化指标,完成股骨骨密度和腰椎骨密度测定,进行超声心动图检查,计算得出左室质量指数。进行单因素方差分析和多因素多元线性回归分析。 结果与结论：随着骨量减少,左室质量指数逐渐增大,左心室肥厚发生率上升,差异有显著性意义(P < 0.05)。以左室质量指数为因变量,多元线性回归分析显示,年龄、收缩压、高血压病程、腰椎骨密度或股骨骨密度与左室质量指数独立相关。结果提示在老年女性人群中,骨密度可能是影响左室质量指数的独立危险因素。     

股骨近端髓腔闪烁指数与股骨颈骨密度的关系

背景：髋关节成形患者具有较高的骨质疏松症患病率,骨质疏松症影响假体存活率,髓腔闪烁指数与骨密度均随年龄变化。 目的：探讨股骨近端髓腔闪烁指数与股骨颈骨密度的关系,提高对骨质疏松症的关注。 方法：回顾性研究57例髋关节成形患者的骨盆X射线正位片的股骨近端髓腔闪烁指数和股骨颈骨密度,探讨二者的相关性。 结果与结论：57例髋关节成形患者的股骨近端髓腔闪烁指数为1.8-4.8(3.1±0.7);髓腔闪烁指数< 3者23例,髓腔闪烁指数为3-4.7者33例,髓腔闪烁指数> 4.7者1例。年龄对髓腔类型有影响,> 60岁组烟囱型髓腔显著性多于≤ 60岁组,髓腔闪烁指数≥ 3组的骨密度显著高于髓腔闪烁指数< 3组。随着年龄增高,股骨颈骨密度降低,> 60岁组患者的股骨颈骨密度为(0.590±0.092) g/cm2,显著低于≤ 60岁组患者的股骨颈骨密度(0.751±0.235) g/cm2(P =0.000),比较发现随骨密度降低,髓腔闪烁指数均值变小。因此股骨颈骨密度与髓腔闪烁指数显著相关。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Low handgrip strength is associated with low bone mineral density and fragility fractures in postmenopausal healthy Korean women

Osteoporosis is a widely recognized health problem in postmenopausal women. Osteoporotic fractures reduce independency, limit daily living activities, and increase the mortality rate. Epidemiological studies have demonstrated that low handgrip strength is a risk factor for functional limitations and disabilities, and all-cause mortality. We investigated the relationship between handgrip strength and bone mineral density (BMD) of the spine, femur neck, and total hip, as well the relationship between handgrip strength and previous fragility fractures in 337 healthy postmenopausal Korean women (mean age of 59.5 ± 6.8 yr) who were free of diseases or medications affecting bone metabolism. Age and handgrip strength were associated with BMD of the spine, femur neck, and total hip in multiple regression models. Low handgrip strength (odds ratio [OR], 0.925; range, 0.877 to 0.975; P = 0.004) and low femur neck BMD (OR, 0.019; range, 0.001 to 0.354; P = 0.008) were independent predictors of previous fragility fractures in a multiple regression model. Our results demonstrate that low handgrip strength is associated with low BMD of the spine, femur neck, and total hip, and with increased risk of previous fragility fractures.     

Farnesyl diphosphate synthase: a novel genotype association with bone mineral density in elderly women

OBJECTIVE: We evaluated the association between a single nucleotide polymorphism in the farnesyl diphosphate synthase gene (FDPS), BMD and bone turnover markers. METHODS: Two hundred and eighty-three community-dwelling Caucasian women aged 65 or older were screened from the greater Boston area. A validated FDPS SNP (rs2297480, A/C) was genotyped and evaluated for effect on bone mineral density (spine, hip, forearm) and bone turnover markers (urine N-telopeptide cross-linked collagen type 1, osteocalcin and bone-specific alkaline phosphatase). RESULTS: BMD was lower at all sites measured in women with the C/C or C/A genotypes. Statistically significant differences (p<0.05) were found at the PA spine, trochanter, distal radius, and proximal ulna after adjustment for age and BMI. No significant differences were found in bone turnover markers. CONCLUSION: These findings suggest that a single nucleotide polymorphism in the FDPS gene (rs2297480) may be a genetic marker for lower BMD in postmenopausal Caucasian women.     

Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women

Objective: This study was to investigate whether the effect of lean and fat mass component on bone mineral density (BMD) differs between pre- and postmenopausal women. Materials and methods: Subjects were 360 pre- and 193 postmenopausal Japanese women with right side dominance. Age, height, and years since menopause (YSM, in postmenopausal women) were recorded. Body fat and lean body mass were measured by whole body scanning with dual-energy X-ray absorptiometry (DEXA). BMD of the vertical axis (L2-4 of the lumbar spine, pelvis, bilateral legs, and total body) and horizontal axis (arms) were also measured by DEXA. Results: In premenopausal women, lean body mass was independently correlated with BMD of the left arm (partial correlation COEFFICIENT=0.417), right arm (0.430), L2-4 (0.285), pelvis (0.276), left leg (0.403), right leg (0.412), and total body (0.377) (P<0.001). However, body fat mass was not correlated with several BMD sites except for pelvis BMD (0.187, P<0.01). In postmenopausal women, body fat mass was independently correlated with BMD of the left arm (0.248, P<0.01), L2-4 (0.188, P<0.05), pelvis (0.263, P<0.01), left leg (0.228, P<0.01), right leg (0.319, P<0.001), and total body (0.188, P<0.01)). However, lean body mass was correlated with BMD in only three segmental regions including left arm (0.175), right arm (0.217), and left leg (0.210; P<0.05). Conclusion: Lean body mass is a significant determinant of BMD in premenopausal women, while body fat mass is a significant determinant in postmenopausal women.     

人工股骨头置换治疗高龄股骨转子间骨折与股骨颈骨折的比较

背景：对于移位明显的股骨颈骨折采用股骨头置换已成为共识,而对于股骨转子间骨折采用人工股骨头置换仍存在分  歧。 目的：通过比较人工股骨头置换治疗高龄股骨转子间骨折与股骨颈骨折的疗效及预后,评价双极骨水泥型人工股骨头置换治疗高龄股骨转子间骨折的效果。 方法：2005-06/2009-06采用人工股骨头置换治疗高龄股骨转子间骨折和股骨颈骨折患者共112例,其中股骨转子间骨折组52例,股骨颈骨折组60例。对两组患者的手术时间、出血量、下地负重时间和髋关节功能进行比较分析。 结果与结论：置换后随访12~39个月。按Harris评分评估髋关节功能,股骨转子间骨折组优22例,良25例,可3例,差1例,优良率为92.1%;股骨颈骨折组优28例,良25例,可4例,差1例,优良率为91.3%。股骨颈骨折组的手术时间显著短于股骨转子间骨折组(P < 0.05),出血量显著低于股骨转子间骨折组(P < 0.05)。但下地负重时间和疗效优良率两组差异无显著性意义。提示人工股骨头置换可作为治疗高龄股骨转子间不稳定骨折的主要方法。     

Relationship of head lean mass to regional bone mineral density in elderly postmenopausal women

OBJECTIVES: This study investigated the relationship of head lean mass to bone mineral density (BMD). METHOD: Subjects were 102 elderly women (> or =65-years-old) and 123 middle-aged postmenopausal women (<65-years-old) with right-side dominance. Age, height, weight, and years since menopause (YSM) were recorded. Lean mass of the head, arm, trunk, leg, and total body were measured by dual-energy X-ray absorptiometry (DEXA). BMD of the same regions were measured by DEXA. RESULTS: In elderly women, head lean mass was positively correlated with BMD of the head (r=0.389, P<0.01), left arm (r=0.235, P<0.05), right arm (r=0.280, P<0.05), lumbar spine (L2-4) (r=0.411, P<0.001), pelvis (r=0.490, P<0.001), left leg (r=0.572, P<0.001), right leg (r=0.558, P<0.001), and total body (r=0.529, P<0.001). These relationships remained significant after adjusting for age, height, and YSM. In addition, the strength of correlation of head lean mass with BMD was higher than those of other regional lean mass with respective BMD. In middle-aged women, strength of correlation of head lean mass with BMD was loose (r< or =0.238), while regional lean mass was more correlated with respective regional BMD. CONCLUSION: Factors related to lifestyle associated with higher (lower) head lean mass may contribute to higher (lower) BMD in elderly postmenopausal women.