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.     

In-vivo studies on Haemaccel-fibronectin interaction in man

An enzyme-linked immunoassay has been recently set up for direct measurement of the binding capacity of plasma fibronectin to gelatin. This binding capacity could be completely inhibited in vitro by an eight-fold excess of gelatin, of Haemaccel, but not of Geloplasma. On the contrary, the levels of immunoreactive fibronectin measured by laser nephelometry did not change, in presence of 10 to 1000 micrograms ml-1 of gelatin, of Haemaccel or of Geloplasma. When infused into normal volunteers, Haemaccel provoked a strong and immediate inhibition of the plasma fibronectin binding capacity to gelatin. This inhibition was dose-dependent and maximal after infusion of 500 ml of Haemaccel. Twenty-four hours after this infusion, there was a progressive recovery of the gelatin-binding capacity, which was almost completely achieved 96 h later. The formation of complexes between Haemaccel and fibronectin was demonstrated by gel filtration chromatography and by affinity chromatography. Immunoreactive plasma fibronectin levels remained unchanged up to 24 h after infusion of 500 ml of Haemaccel. A transient decline to 50% of its initial value then occurred the second day after the infusion. Therefore, a delay existed between the formation of fibronectin-Haemaccel complexes and their elimination from the bloodstream. This delay decreased when smaller volumes of Haemaccel were infused, which strongly suggests that plasma fibronectin is cleared by means of Haemaccel and does not seem to play a role of opsonin in these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

X-linked hypophosphatemia: Normal renal function despite medullary nephrocalcinosis 25 years after transient vitamin D2-induced renal azotemia

Nephrocalcinosis (NC) detected by ultrasound is a recognized abnormality for some patients with X-linked hypophosphatemia (XLH) who received vitamin D₂ and inorganic phosphate therapy, but is commonly observed in XLH patients treated with 1,25-dihydroxyvitamin D₃ and inorganic phosphate supplementation. Nevertheless, long-term follow-up of kidney function in XLH patients with NC detected ultrasonographically has not been reported. We investigated two women with XLH, ages 31 (patient 1) and 39 (patient 2) years, each of whom had suffered at least one documented episode of vitamin D₂-induced hypercalcemia and renal azotemia during childhood. Patient 2 had also been treated with inorganic phosphate. No medications for XLH had been taken during adulthood. Renal ultrasonography at our institution demonstrated marked bilateral medullary NC in both women. No other explanation was found for their NC that apparently occurred several decades earlier from medical therapy for XLH. Detailed studies (including creatinine clearance, β₂-microglobulin excretion, and fasting urinary osmolality and acidification) revealed no impairment of kidney function in either patient. Our findings indicate that subradiographic medullary NC acquired during medical therapy for XLH may persist for decades, but with no adverse renal sequelae. Definitive (long-term) assessment of kidney function in the XLH population with NC, however, will be necessary to fully understand the risk of current medical treatment for this most common heritable form of rickets.     

Evaluation of vertebral volumetric vs. areal bone mineral density during growth

Bone mineral “density” (BMD) measured by dual-energy X-ray absorptiometry (DEXA) does not represent the volumetric density (grams per cubic centimeter), but rather the areal density (grams per square centimeter). This distinction is important during growth. The purpose of this study was to measure vertebral dimensions in cadavers of young pigtail macaques (Macaca nemestrina), and to derive equations to predict the volumetric bone density from noninvasive measurements. We measured the areal bone density by DEXA, vertebral volume by underwater weighing, mineral content by ashing, dimensions of lumbar vertebrae by calipers, and dimensions of vertebrae by radiography. Somatometric measurements of the female lumbar vertebral bodies showed that the shape changed during growth. The bone mineral content from the densitometer correlated significantly with the ash weight (r = 0.99, error 8.7%). The correlation coefficient between the volumetric bone mineral density and areal BMD measurement was significant (r = 0.68, p < 0.0001) with a 9.5% error; this improved significantly to 0.82 (7.2% error) when the BMD was divided by the vertebral depth from the radiograph. Areal BMD showed a strong correlation with age (r = 0.82, p < 0.0001), with an average increase of 7.4%/year. In contrast, volumetric mineral density showed a weak relationship with age (r = 0.43, p < 0.01), for an average increase of 1.5%/year. When studying bone mineral density during growth, the differences between volumetric and areal bone mineral density should be taken into consideration. (