Spinal Trabecular Bone Loss and Fracture in American and Japanese Women

This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the K₂HPO₄ liquid phantom in 538 Americans aged 20–85 years, and with the B-MAS200 phantom in 577 Japanese aged 20–83 years. These BMD were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111 postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1 mg/cm³ in women aged 20–24 years, 40–44 years, 60–64 years, respectively. In premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion, Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women. Received: 18 December 1995 / Accepted: 23 September 1996     

Associations of Early Premenopausal Fractures with Subsequent Fractures Vary by Sites and Mechanisms of Fractures

In a retrospective population-based study we assessed whether and how self-reported former fractures sustained at the ages of 20–34 are associated with subsequent fractures sustained at the ages of 35–57. The 12,162 women who responded to fracture questions of the baseline postal enquiry (in 1989) of the Kuopio Osteoporosis Study, Finland formed the study population. They reported 589 former and 2092 subsequent fractures. The hazard ratio (HR), with 95% confidence interval (CI), of a subsequent fracture was 1.9 (1.6–2.3) in women with the history of a former fracture compared with women without such a history. A former low-energy wrist fracture was related to subsequent low-energy wrist [HR = 3.7 (2.0–6.8)] and high-energy nonwrist [HR = 2.4 (1.3–4.4)] fractures, whereas former high-energy nonwrist fractures were related only to subsequent high-energy nonwrist [HR = 2.8 (1.9–4.1)] but not to low-energy wrist [HR = 0.7 (0.3–1.8)] fractures. The analysis of bone mineral density (BMD) data of a subsample of premenopausal women who underwent dual x-ray absorptiometry (DXA) during 1989–91 revealed that those with a wrist fracture due to a fall on the same level at the age of 20–34 recorded 6.5% lower spinal (P= 0.140) and 10.5% lower femoral (P= 0.026) BMD than nonfractured women, whereas the corresponding differences for women with a former nonwrist fracture due to high-energy trauma were −1.8% (P= 0.721) and −2.4% (P= 0.616), respectively. Our results suggest that an early premenopausal, low-energy wrist fracture is an indicator of low peak BMD which predisposes to subsequent fractures in general, whereas early high-energy fractures are mainly indicators of other and more specific extraskeletal factors which mainly predispose to same types of subsequent fractures only. Received: 21 February 1996 / Accepted: 24 September 1996     

人皮质骨矿化基质中骨盐框架结构

目的：研究人皮质骨矿化基质中骨盐的框架结构及框架中骨微间隙。方法：应用透射电镜、场发射扫描电镜观察、电脑图像分析及能谱分析，分析无骨病成人长骨、扁骨２００例骨盐分布特征。结果：骨盐框架结构由微柱、微梁、微小梁、弓状梁、致密点、隔板和骨微间隙构成。骨微间隙由洞、内衬和壁组成，洞平均直径为８４．４±７５．６ｎｍ，与骨小管相比有显著差异（Ｐ值＜０．００１），平均密度为１１～１７个／μｍ２，与骨小管之比超过１０：１。骨盐分针形结晶和微颗粒结晶。结论：骨盐框架结构及骨微间隙是骨盐在人皮质骨矿化基质中的存在形式，可能与骨盐吸收、沉着有关。     

The influence of partial gastrectomy on biochemical parameters of bone metabolism and bone density

Summary Since it has been suggested that gastric resections are followed by changes in bone metabolism, the aim of our study was to determine the biochemical parameters of bone metabolism and radial and lumbar bone density in 15 male ulcus patients treated by partial gastrectomy (Billroth II). Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography was statistically significantly lower (P < 0.04) in the patient group, whereas the peripheral bone mass of the distal part of the nondominant forearm measured by single-photon absorptiometry showed no statistically significant difference. In addition, a marked increase in alkaline phosphatase (P < 0.002) and urinary excretion of hydroxyproline (P < 0.003) was found in the gastrectomy group, whereas the 25-hydroxy-vitamin D levels were found to be significantly decreased (P < 0.04). Osteocalcin, a biochemical marker for osteoblast activity, and the carboxy-terminal propeptide of type I procollagen (PICP), a marker of collagen formation, were slightly but not significantly higher in gastrectomy-treated patients. The serum parathyroid hormone levels were similar in both groups. As none of the patients had any radiologic evidence of osteopenia, the changes in biochemical parameters of bone metabolism and bone mass in patients who had undergone partial gastrectomy could be a marker of latent bone loss.Abbreviations DPA/SPA dual/single-photon absorptiometry - BMD bone mineral density - QCT quantitative computed tomography - PICP carboxy-terminal propeptide of type I procollagen - 250HD₃ 25-hydroxy-vitamin D - iPTH parathyroid hormone - OC osteocalcin - BMC bone mineral content     

Effects of Clodronate on Cortical and Trabecular Bone in Ovariectomized Rats on a Low Calcium Diet

The aim of this study was to evaluate the contribution of a low calcium diet to the cortical and trabecular osteoporosis seen in ovariectomized rats after 7 weeks on a low calcium diet and to investigate the effects of the bisphosphonate clodronate on this development of osteoporosis. Thirty-six mature, female Wistar rats were randomized into four groups: Ovx−B (bisphosphonate) and Ovx−C (control) were ovariectomized, and Sham−Ca (low calcium) and Sham+Ca (normal calcium) were sham operated. The first three groups were fed a low calcium diet (0.01%) and Sham+Ca normal rat chow (Ca 1.1%). The Ovx−B received 10 mg/kg s.c. clodronate daily for nine weeks, and Ovx−C, Sham−Ca, and Sham+Ca received the same volumes of saline. Bone mineral turnover measured as ⁸⁵Sr-uptake was increased in all low calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and ash weight than the other groups, and Ovx−C had higher dry weight compared with Ovx−B and Sham−Ca. Calcium content was lower in both Ovx groups compared to both Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in Ovx−B compared with Ovx−C. In the femoral shaft, Sham+Ca had significantly higher ultimate bending moment, energy absorption, and deflection compared to the other three groups. Ultimate bending moment was higher in Sham−Ca than in Ovx−C. Stiffness was increased in both Sham+Ca and Ovx−B compared to Ovx−C. The maximum stress in the femoral midshaft was higher in Sham+Ca than in the other groups, and higher in Ovx−B than in Ovx−C. Histomorphometry showed increased medullary area in all low calcium groups compared to Sham+Ca and larger cortical area in Sham+Ca and Ovx−B compared to Ovx−C. Compared to Sham+Ca the trabecular bone volume was decreased to 30% in Sham−Ca and to 9% in Ovx−C, but was unchanged in Ovx−B. The low calcium diet generally increased bone mineral turnover and reduced the tibial bone volume. Femoral changes led to a reduction of cortical fracture strength and maximal stress. Ovariectomy in addition to a low calcium diet reduced femoral strength even more. Daily injections of clodronate to ovariectomized rats on a low calcium diet increased femoral shaft stiffness and maximum stress, and clodronate preserved both trabecular and cortical tibial bone volume completely. Received: 11 June 1996 / Accepted: 5 March 1997     

四种可溶性载体对骨形态发生蛋白在小鼠体内诱导成骨活性的影响

以四种可溶性物质作为牛骨形态发生蛋白（ｂＢＭＰ）的载体，通过实验观察哪种物质是ｂＢＭＰ的有效缓释载体。将聚乙烯吡咯烷酮（ＰＶＰ）、葡聚糖、羟乙基淀粉（ＨＥＳ）、甘露醇分别与等量ｂＢＭＰ复合后，注射入小鼠股部肌肉，观察组织学成骨及测定标本内钙含量。结果，ｂＢＭＰ／ＰＶＰ有良好成骨，吸收较快，未见炎症及排斥反应，其混悬液较稳定，具有良好的适针性及可注射性，ｂＢＭＰ／甘露醇只有很低成骨率。其余各组未见成骨。ＰＶＰ对ｂＢＭＰ具有满意助溶、助悬及缓释载体作用，对ｂＢＭＰ活性无损害，生物相容性好。     

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.     

Bone mineral status in paraplegic patients who do or do not perform standing

Bone mineral density (BMD) was assessed by dual-photon X-ray absorptiometry at the lumbar spine (L3, L4), the proximal femur and the femoral shaft, and by single-photon absorptiometry at the forearm in 53 patients with complete traumatic paraplegia of at least 1 year's duration and in age- and sex-matched healthy controls. The patients did (n=38) or did not (n=15) regularly perform passive weightbearing standing with the aid of a standing device. Compared with the controls, the BMD of paraplegic patients was preserved in the lumbar spine and was markedly decreased in the proximal femur (33%) and the femoral shaft (25%). When considering all patients performing standing, they had a better-preserved BMD at the femoral shaft (p=0.009), but not at the proximal femur, than patients not performing standing. BMD at the lumbar spine (L3,L4) was marginally higher in the standing group (significant only for L3;p=0.040). A subgroup of patients performing standing with use of long leg braces had a significantly higher BMD at the proximal femur than patients using a standing frame or a standing wheelchair (p=0.030). The present results suggest that passive mechanical loading can have a beneficial effect on the preservation of bone mass in osteoporosis found in paraplegics.     

Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras

Localization of bone marrow-originated cells in the central nervous system (CNS) of the rat was investigated by using bone marrow chimeras. In order to do this, Lewis rats which carry major histocompatibility complex (MHC) class I antigens haplotype 1 (RT1.Al) were reconstituted with (Lew X PVG)F1 (RT1.Al/c) bone marrow cells after lethal irradiation. Transferred bone marrow cells were detected by immunohistochemical staining using a monoclonal antibody, OX27, specific for haplotype c of rat MHC class I antigens (RT1.Ac). The spleen and thymus of chimeric rats were fully reconstituted with transferred F1 cells 4 weeks after bone marrow transplantation. At this stage, mononuclear cells in the subarachnoid space of the CNS expressed OX27 antigen indicating that they were of bone marrow origin. A few OX27-positive blood cells were scattered in the CNS parenchyma 4-12 weeks after reconstitution. Ramified microglia, however, remained OX27-negative. Bone marrow-derived microglia were not observed throughout the period of examination until 24 weeks. In addition, experimental allergic encephalomyelitis (EAE) was induced in chimeric rats in order to augment the expression of MHC class I antigens on microglia. Even under this condition, no OX27-positive microglia were observed. Taken together, ramified microglia might be of neuroectodermal origin and there is little possibility that the microglia are derived from the bone marrow. However, if the ramified microglia are derived from blood cells, the microglia may be expected to have characteristic cell kinetics from the following points: (1) the precursor cells of the microglia may enter the CNS only at the perinatal stage; and (2) even under the condition in which lymphocytes and macrophages enter the CNS as observed in EAE, the precursor cells of the microglia are not supplied from the blood.