中老年人骨密度骨代谢相关因素探讨

目的 探讨中老年人骨密度骨代谢相关因素.方法 选取159例骨质疏松（OP）患者及97例年龄、体重指数、身高等相匹配的健康对照者测量正位第二至第四腰椎（L2～4）、左侧股骨近端（Neek、Ward三角、Troch）的骨密度（BMD）;测定碱性磷酸酶（ALP）、骨钙素（BGP）、抗酒石酸酸性磷酸酶（TRAP）、尿Ⅰ型胶原降解产物（CTX）、肌酐（Cr）浓度.结果 骨质疏松患者正位L2～4、Neek、Ward三角、Troch骨密度低于对照组.骨质疏松组血中ALP、BGP、 TRAP浓度显著高于对照组（P＜0.05、P＜0.05、P＜0.05）;尿中CTX浓度显著高于对照组（P＜0.05）.结论 骨质疏松患者各部位BMD改变不同,其骨改变特点是骨吸收增加,骨转化率增加;TRAP、CTX 、BGP、ALP是反映骨质疏松患者骨代谢较敏感的生化指标.     

GnRH类似物治疗对男性前列腺癌患者骨丢失的影响

目的探讨GnRH类似物治疗对老年男性前列腺癌患者骨量丢失、骨转换及身体成分的影响。方法确诊前列腺癌患者33人,同年龄健康男性35人,分别在治疗前、治疗12个月后测定受试者腰椎24（L2-4）、左股骨颈（FN）、全髋（Total Hip）的骨密度及全身总骨量、体脂（Total fat mass）和肌肉（Total lean mass）含量,并检测血清骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、250HD、尿Ⅰ型胶原C端交联物（CTX）等骨转换指标。结果前列腺癌GnRH类似物治疗组和对照组相比基线水平的骨密度和骨代谢各项指标间都没有显著性差异,GnRH类似物治疗12个月后,血FSH、T、E2分别下降了66．0％、87．5％和75．0％（P〈0．01）,血PSA水平下降100％（P〈0．001）;腰椎、股骨颈、全髋及全身骨量丢失率分别为-2．05％、-3．55％、-3．47％和-3．64％,与对照组相比各部位骨量的下降均有显著性差异（P〈0．05）;Total fat mass和Total lean mass变化率分别为＋12．6％和-10．8％,与对照组相比lean mass下降具有显著性差异（P〈0．05）;尿CTX／Cr和血250HD变化率分别为＋54．71％和-43．75％,与对照组相比变化率有显著性差异（P〈0．05）。6个月时骨转换标记物尿CTX／Cr的变化率与12个月时骨丢失率呈负相关。结论前列腺癌患者接受GnRH类似物治疗后出现明显的骨转换加速、骨量丢失增加及身体脂肪肌肉成分的改变,对这些病人及时监测骨密度和骨转换指标有利于早期诊断早期防治。     

老年2型糖尿病患者骨密度和骨代谢研究

目的探讨老年2型糖尿病患者骨密度（BMD）和骨代谢的特点及其影响因素。方法选择65例老年2型糖尿病患者和68例健康老年体检者,应用双能X-线骨密度仪测定腰椎（L1-L4）和股骨颈BMD,同时检测空腹血清骨钙素（BGP）、血钙（Ca）、血磷（P）、甲状旁腺激素（PTH）和晨尿脱氧吡啶啉（DPD）。结果糖尿病组的腰椎、股骨颈BMD和BGP低于健康对照组,PTH、P和DPD高于健康对照组。结论老年2型糖尿病患者骨形成减少,骨吸收增加,骨质疏松症发生率高。     

高血糖状态对骨形成和骨吸收作用及骨密度的影响

目的 探讨不同血糖水平对骨形成、骨吸收和骨密度的影响.方法 对糖尿病组(DM)148例,葡萄糖耐量低减组(IGT)30例,空腹血糖受损组(IFG)30例,健康对照组(Control)50例,分别测定血浆葡萄糖(BG)、糖化血红蛋白(HbA1c)、血清骨钙素(BGP)、尿脱氧吡啶啉(DPD)/肌酐(Cr)、腰椎(L2、L3、L4)和髋部(股骨颈、Ward三角、大转子)骨密度(BMD),并对上述指标进行T检验和方差分析.结果 四组间方差分析显示BMD在Ward三角、L4差异有统计学意义(P<0.05).血清BGP水平在四组呈递增趋势,尿DPD/Cr水平在四组呈递减趋势,方差分析显示尿DPD/Cr水平差异有显著统计学意义(P<0.001).尿DPD/Cr水平随HbA1c水平递增逐渐增高.结论 糖尿病的前期阶段(IGT),骨吸收已呈现高于同龄正常人水平,糖尿病患者骨形成低于同龄正常人而骨吸收高于同龄正常人,骨平衡呈现负平衡,骨量逐渐丢失;IGT开始骨密度已较正常人低,良好的血糖控制对减少骨吸收和延缓骨量下降具有保护作用.应在糖调节受损的早期阶段对骨质疏松进行干预治疗.     

血清性激素水平与老年男性骨代谢指标及骨密度的关系

目的：探讨老年男性血清性激素表达水平与骨代谢指标及骨密度之间的关系。方法：收集老年男性患者230例,年龄65～95岁,分别测定雌二醇（E2）、睾酮、游离睾酮（FT）、性激素结合球蛋白（SHBG）、脱氢表雄酮（DHEA）、骨钙素、骨碱性磷酸酶（BALP）、25-羟维生素D3及尿Ⅰ型胶原交联氨基末端肽（NTX）等指标,同时利用双能X线分别测定髋关节及腰椎（L1～L4）的骨密度,分析老年男性骨密度、骨代谢指标与血清性激素以及年龄与骨密度的相关性。结果：血清E2、FT与腰椎及髋关节的骨密度呈正相关,而睾酮、SHBG、DHEA与骨密度无关。血清E2、FT与骨代谢指标NTX、BALP呈负相关,血清E2与25-羟维生素D3呈正相关,而睾酮、SHBG、DHEA与骨代谢指标NTX、BALP无关。年龄与腰椎L1、L2、L4、L1～4及髋部骨密度呈负相关,与腰椎L3骨密度无关。结论：老年男性骨密度的变化受性激素中FT、E2表达水平的影响,而受E2的影响程度超过雄激素。血清FT及血清E2的水平可作为老年男性骨质疏松症的独立观察指标。     

雌激素对老年雄性大鼠植入骨新形成的影响

目的　研究雌激素对老年雄性哺乳动物的植入骨的新生骨骨面积及对全身骨代谢的影响。方法　骨基质骨片植入老年雄性大鼠 ,观察注射雌激素组、雄激素组和对照组骨组织计量学、骨生物力学、尿脱氧吡啶啉 /肌酐 (Dpd/Cr)比值 ,以及血和尿的钙、磷等的变化。结果 ( 1)新生骨骨面积 :雌激素组和雄激素组均比对照组明显增高 (P <0 0 5 ) ,雌激素组和雄激素组之间差异无显著性。 ( 2 )破骨细胞数 :雌激素组 ( 5 5± 3)个 /mm2 和雄激素组 ( 5 3± 3)个 /mm2 均显著高于对照组 ( 40± 3)个 /mm2 (P≤ 0 0 0 2 ) ,雌激素组和雄激素组之间差异无显著性。 ( 3)尿Dpd/Cr比值 (mmol/mol) :注药后5周 ,对照组 (注射溶剂 )比注药前明显升高 ( 198± 2 0vs 10 4± 7) ,雌激素组 ( 114± 16 )和雄激素组 ( 118± 19)均比对照组 ( 198± 2 0 )明显减低 ,与注药前无明显差异 ,雌激素和雄激素组之间差异无显著性。结论　雌激素和雄激素不仅能刺激老年雄性大白鼠植入骨的新生骨骨面积增加 ,也能抑制全身骨骼的骨吸收速率。本实验条件下 ,这两方面的影响 ,雌激素和雄激素组之间未见明显差异     

小剂量生长激素短期补充治疗对老年男性骨转换标志物及骨密度的影响

目的探讨小剂量生长激素(GH)短期补充治疗对老年男性骨转换标志物及骨密度的影响。方法从体检及住院患者中选择37例60~79岁的血清胰岛素样生长因子-1(IGF-1)水平低下的老年男性,随机分为治疗组19例和对照组18例。治疗组接受连续6月的小剂量重组GH补充治疗,对照组无特殊处理。所有患者治疗前后均检查IGF-1、骨钙素(OC)、骨碱性磷酸酶(BALP)、尿吡啶啉/肌酐(U-Pyr/Cr)、尿脱氧吡啶啉/肌酐(UDPyr/Cr)水平及腰椎1~4(L1~L4)、股骨颈骨密度(BMD)。结果 6月后,治疗组IGF-1、OC、BALP、U-Pyr/Cr、U-DPyr/Cr均较对照组有显著升高(P0.01或P0.05),2组L1~L4、股骨颈BMD差异无统计学意义(P均0.05)。结论短期小剂量GH补充可促进老年男性骨转换,但不增加BMD。     

唑来膦酸联合经皮椎体成形术治疗老年骨质疏松椎体压缩性骨折的疗效及对患者骨密度、骨代谢生化指标的影响

目的 探究唑来膦酸联合经皮椎体成形术治疗老年骨质疏松椎体压缩性骨折(OVCF)的疗效及对患者骨密度、骨代谢生化指标的影响。方法 回顾性收集老年骨质疏松OVCF患者118例的临床资料。采用随机数字表法分为对照组和观察组各59例。对照组仅接受经皮椎体成形术(PVP),观察组予以PVP+唑来膦酸治疗。观察两组疼痛评分、骨密度、骨代谢指标水平及腰椎功能。结果 两组年龄、性别、椎体骨折数及病程均无统计学差异(P>0.05)。治疗前，两组疼痛评分、骨密度及骨代谢指标差异无统计学意义(P>0.05)。两组治疗后疼痛评分均显著降低，且观察组降低更为显著(P<0.05)。治疗后，两组骨密度明显上调，且观察组升高更为显著(P<0.05)。治疗前，两组骨代谢指标Ⅰ型前胶原氨基末端肽(PINP)、骨碱性磷酸酶(BALP)、β-胶原特殊序列(CTX)及抗酒石酸酸性磷酸酶(TRACP)水平无统计学差异(P>0.05)。治疗后，两组PINP、BALP水平明显上调，β-CTX及TRACP水平显著下调，且观察组骨代谢指标变化幅度显著大于对照组(P<0.05)。治疗后，两组腰椎功能障碍...     

绝经后妇女MMP-2和TIMP-2水平及其与骨密度和骨代谢指标的关系

目的 探讨绝经后妇女血清基质金属蛋白酶2（MMP-2）和组织金属蛋白酶抑制因子2（TIMP-2）水平及其与骨密度和骨代谢指标的关系。方法 对192名48～65岁绝经后妇女用酶联免疫吸附法（ELISA）测定的血清MMP-2、TIMP-2以及骨碱性磷酸酶（BAP）、骨钙素、Ⅰ型胶原交联C端肽（CTX），尿Ⅰ型胶原交联N端肽（NTX），计算MMP-2／TIMP-2比值，用双能X线吸收法（DEXA）测定腰椎正位，股骨颈，Ward三角和大粗隆的骨密度，按WHO标准将绝经后妇女分为骨密度正常、低骨量和骨质疏松3组。结果 （1）绝经后妇女骨质疏松患者血清MMP-2的水平（1388±121）μg／L高于骨密度正常组（1126±141）μg／L（P〈0．05），而TIMP-2的水平（44．3±38．2）μg／L稍低于骨密度正常组（47、3±30．2）μg／L（P〉0．05）。（2）血清MMP-2和MMP-2／TIMP-2比值与腰椎正位和Ward三角骨密度、血清BAP和骨钙素呈负相关（均P〈0．05），和尿NTx／Cr呈正相关（P〈0．05），MMP-2／TIMP-2比值还与股骨颈骨密度呈负相关（P〈0．05）。TIMP-2与腰椎正位和Ward三角骨密度、血清BAP和骨钙素呈正相关（均P〈0．05），和尿NTX／Cr呈负相关（P〈0．05）。在校正年龄和体重指数后，TIMP-2与腰椎正位骨密度和骨钙素无相关性（P〉0．05）。（3）骨质疏松组中血清MMP-2和MMP-2／TIMP-2比值与腰椎正位、股骨颈和Ward三角骨密度、血清BAP和骨钙素呈负相关（均P〈0．05），和尿NTX／Cr呈正相关（均P〈0．05），TIMP-2和Ward三角骨密度和BAP呈正相关（均P〈0．05）；在低骨量组中仅MMP-2与腰椎正位和Ward三角骨密度、骨钙素呈负相关（P〈0．05），和尿NTX／Cr呈正相关（P〈0．05），MMP-2／TIMP-2比值与Ward三角骨密度和血清BAP呈负相关（均P〈0．05）。结论 绝经后女性尤其是骨质疏松症妇女血清MMP-和MMP-2／TIMP-2比值与骨密度和骨代谢指标BAP、骨钙素和尿NTX／Cr具有关联性，血清MMP-2和MMP-2／TIMP-2比值增高可能为绝经后骨质疏松症伴随骨代谢转换过程增快的表现。     

强直性脊柱炎合并骨质疏松症患者临床特点、骨密度及骨代谢相关指标的研究

目的探索强直性脊柱炎(AS)患者合并骨质疏松症的发病机制及AS患者骨密度和骨代谢变化的相关因素。方法收集189例AS患者临床症状、体征、实验室检查、影像学检查结果,与健康对照组进行对照并进行相关性分析。结果 189例AS患者腰椎、股骨颈、Word’s三角、粗隆的骨密度均与骶髂关节相分级、急时相反应物红细胞沉降率(ESR)、C反应蛋白(CRP)呈负相关,P值分别<0.01、<0.05和<0.05。AS患者血清骨钙素(BGP)与枕墙距、骨特异性碱性磷酸酶(BALP)、Ⅰ型胶原羧基端前肽(CICP)、甲状旁腺激素(PTH)呈正相关,P值分别<0.05、<0.05、<0.01和<0.05。与ESR、Ⅰ型胶原羧基端交联肽(CTX)、尿脱氧吡啶啉(尿DPD)呈负相关,P值分别<0.01、<0.01和<0.05。PTH与年龄、尿DPD呈负相关,P值均<0.01。男性患者BALP较女性更低,P<0.01,其与枕墙距、CICP呈正相关,P值分别<0.05和<0.01,与CTX呈负相关,P<0.01。CICP与骶髂关节相分级、CTX、尿DPD呈负相关,P值分别<0.05、<0.01和<0.05;与BGP呈正相关,P<0.01。CTX与年龄呈负相关,P<0.01;与骶髂关节相分级呈正相关,P<0.01。HLA-B27阳性者CICP值低于阴性者,CTX值则高于阳性者,P值分别<0.05和<0.01。结论 AS患者BGP与BALP、PTH、CICP、CTX、尿DPD之间相互交织成网状对骨代谢造成影响,其启始的触发点为全身或局部的免疫反应,而HLA-B27通过抑制骨胶原蛋白的合成及促进其分解加速了骨破坏,其机理尚待进一步深入研究。     

Metabolic bone disease and bone quality

On the progress of study concerned with pathology of metabolic bone disease such as osteoporosis, it has been known that most of bone strength can be explained by bone volume. As bone volume can be determine by bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA), it has been widely used for diagnosis of osteoporosis or efficacy of treatment. However, with the advance of bone morphometry, decrease of bone strength or existence of insufficiency fracture is influenced by not only loss of BMD but also deterioration of bone quality especially bone microstructure. In this chapter, we will give an outline of change of bone quality in metabolic bone disease.     

Alcohol-induced bone loss and deficient bone repair

BACKGROUND: Chronic consumption of excessive alcohol eventually results in an osteopenic skeleton and increased risk for osteoporosis. Alcoholics experience not only increased incidence of fractures from falls, but also delays in fracture healing compared with non-alcoholics. In this review the term "alcohol-induced bone disease" is used to refer to these skeletal abnormalities. Alcohol-induced osteopenia is distinct from osteoporoses such as postmenopausal osteoporosis and disuse osteoporosis. Gonadal insufficiency increases the rate of bone remodeling, whereas alcohol decreases this rate. Thus, histomorphometric studies show different characteristics for the bone loss that occurs in these two disease states. In particular, alcohol-induced osteopenia results mainly from decreased bone formation rather than increased bone resorption. Human, animal and cell culture studies of the effects of alcohol on bone strongly suggest alcohol has a dose-dependent toxic effect on osteoblast activity. The capacity of bone marrow stromal cells to differentiate into osteoblasts has a critical role in the cellular processes involved in the maintenance of the adult human skeleton by bone remodeling. Chronic alcohol consumption suppresses osteoblastic differentiation of bone marrow cells and promotes adipogenesis. In fracture healing, the effect of alcohol is to suppress synthesis of an ossifiable matrix, possibly due to inhibition of cell proliferation and maldifferentiation of mesenchymal cells in the repair tissue. This results in the deficient bone repair observed in animal studies, characterized by repair tissue of lower stiffness, strength and mineral content. Current knowledge of cellular effects and molecular mechanisms involved in alcohol-induced bone disease is insufficient to develop interventional strategies for its prevention and treatment. OBJECTIVES: The objectives of this review are 1) to identify the characteristics of alcohol-induced bone loss and deficient bone repair as revealed in human and animal studies, 2) to determine the current understanding of the cellular effects underlying both skeletal abnormalities, and 3) to suggest directions for future studies to resolve current ambiguities regarding the cellular basis of alcohol-induced bone disease.     

Metabolic bone markers and bone cell biology

Various metabolic bone markers have been developed in order to analyze each process of bone resorption and bone formation. By evaluating the two processes using bone markers, an imbalance between bone resorption and formation can be estimated. Metabolic bone markers have already been in clinical use for the early diagnosis and the assessment of treatment efficacy in osteoporotic patients and for the diagnosis of cancer-induced bone diseases. Further elucidation of the mechanisms of formation and secretion, metabolic clearance, diurnal rhythm as well as their changes in various disorders should enable us to evaluate bone turnover at a real-time scale and to utilize for the diagnosis of a variety of metabolic bone diseases.     

Measurements of bone mass and bone density

X-ray-based procedures are available to measure bone mineral density in vitro at almost any skeletal site. These bone density measurements are not useful in the diagnosis of the cause of bone loss but at present are the only tests available for assessing bone mass prior to the occurrence of irreversible changes such as fractures or vertebral compression, which are easily recognizable on x-rays. When fractures are present, the severity of the bone loss and the risk for future fractures can be assessed. Repeated measurements permit estimation of the rate of bone loss, which gives useful information for monitoring treatment effect or course of the disease. Measurement of total body calcium is of less clinical importance because of the predominantly trabecular bone loss that generally occurs in metabolic bone disease. Dual-energy x-ray absorptiometry (DEXA) and quantitative computed tomography (QCT) of the spine are of about equal clinical value in the first approach to the patient with metabolic bone disease, although DEXA allows greater variety in sampling sites. For repeated measurements, DEXA provides better precision at significantly lower radiation burden. For bone mineral measurements, the lumbar spine appears to be the most sensitive skeletal site.     

糖皮质激素与骨

糖皮质激素在临床上应用广泛,但所致的骨质流失、代谢失调等不良反应也限制了其使用.本文对糖皮质激素对骨及其细胞的生理和病理生理作用进行综述,并对其不良反应发生的分子机制进行讨论.     

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A-mFc) in vivo. mBMPR1A-mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A-mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-κB ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A-mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders.     

Androgens and bone

Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs.Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males.In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. Such androgen action on bone is mediated by the AR and ERalpha.     

Ageing and bone

Bone loss by ageing has been investigated from standpoints of systemic abnormality and some deficiency in osteoblastic bone formation. This seminar summarize the involvements of a key molecule of adipocytic differentiation PPAR-gamma, essential IGF-I signaling molecules IRS-1 and IRS-2, and an anti-aging gene klotho in the pathophysiology of age-related osteoporosis.     

Sex differences in cancellous and cortical bone strength, bone mineral content and bone density.

The purpose of this study was to examine sex differences in cancellous and cortical bone strength, bone mineral content (BMC) and bone density of excised cadaver vertebral and phalangeal bones. The samples were age-matched. Bone strength was measured as the mechanical force required to crush or break the bones. Two parameters of bone strength were used on the vertebrae; the force at the first deviation from linearity and the mean force during the consolidation before final failure. The force at first deviation from linearity was not significantly different between the sexes, but there was a significant difference in the consolidation force. The mean men's phalangeal strength was twice that of the women's. BMC and BMC/BW of both types of bone were statistically different between the sexes. Radiographic photodensity measures on the vertebrae showed no sex differences. Cortical diameters of the finger bones were significantly greater in males.