20～75岁妇女血清护骨素、核因子-κB受体活化子配体的变化与年龄、停经、骨生化指标和骨密度的关系

目的　研究血清护骨素 (OPG)和核因子 κB受体活化子配体 (RANKL)与年龄、停经、骨生化指标和骨密度的关系 ,了解影响血清OPG和RANKL的因素。方法　在 5 0 4例 2 0～ 75岁的绝经前和绝经后妇女中 ,以双能X线吸收仪测定腰椎和股骨各处骨密度。按WHO标准 ,将绝经后妇女分为骨量正常、骨量减少和骨质疏松 3组。测定血清骨钙素 (BGP)、尿Ⅰ型胶原交联N端肽 (NTx)、血清OPG和RANKL ,计算RANKL/OPG比值。结果　年龄与血清OPG正相关 (r =0 4 4 2 ,P <0 0 0 1) ,与血清RANKL负相关 (r=- 0 2 6 3,P <0 0 0 1)。绝经后妇女的血清OPG(10 7 6± 3 0 )ng/L明显高于绝经前妇女 (72 0± 1 8)ng/L ,而血清RANKL(4 7± 0 4 )ng/L显著低于绝经前妇女 (5 8± 0 3)ng/L。校正年龄、停经年限和体重指数后 ,血清OPG、RANKL与腰椎和股骨各处骨密度无相关性。血清OPG与尿NTx/肌酐正相关 ;血清RANKL与血清BGP负相关。血清OPG和RANKL在绝经后骨质疏松组、骨量减少组和正常骨量组间差异无显著性。多元逐步回归分析显示 ,年龄、停经年限和骨转换指标是决定血清OPG RANKL系统的独立因素。结论　随年龄而升高的血清OPG可能是人体对抗绝经后骨吸收加快的一个代偿性反应 ,随年龄而下降的血清RANKL可能有益于恢复绝经后妇女的骨     

护骨素基因启动子区T950-C多态性与骨密度及骨代谢的关系

目的探讨绝经后汉族妇女护骨素(OPG)基因启动子区T^950-C多态性与骨质疏松症和骨代谢的关系。方法应用PCR—RFLP测定随机选取的73例绝经后骨质疏松症妇女和61例绝经后正常妇女OPG基因T^950-C的基因型，双能X线骨吸收方法分别测腰椎各椎体和股骨颈髋部的BMD，放射免疫分析法测骨代谢指标。结果所选人群OPG基因T^950-C基因型频率分布在骨质疏松症和绝经正常妇女均符合Hardy-Weinberg定律，而且其基因型在两组研究对象中分布差异无显著性，但汉族妇女T^950-C基因型分布与高加索人种妇女相比有明显差异。在骨质疏松症组CC型的股骨颈BMD低于TT型和TC型，而绝经后正常妇女三种基因型之间BMD无差异。结论OPG基因T^950-C基因型分布存在明显的种族差异。OPG基因T^950-C多态性不能作为中国汉族妇女是否发生骨质疏松症的遗传标志，但对于患有骨质疏松症的中国汉族妇女CC型却能预测骨骨质疏松症的患病程度。     

山茶籽油对广西壮族绝经后妇女护骨素和RANKL水平的影响

目的探讨长期食用山茶籽油对广西壮族绝经后妇女OPG和RANKL水平的影响。方法选取20～80岁的广西壮族妇女,连续5年以上进食食用山茶籽油(ECO)者为ECO组,长期食用花生油和动物油者为NECO组。采用超声定量骨质密度测量仪测量入选者足跟骨超声衰减值(BUA)、酶联免疫吸附试验(ELISA)检测40～80岁妇女血清中OPG和RANKL水平。结果 ECO组和NECO组在20～39岁时,骨质密度随着年龄的增长逐渐增加,随后开始下降,55岁后下降明显,特别是NECO组,并在50岁后两组BUA差异有统计学意义(均P0.05)。在40～54岁时,ECO组和NECO组OPG水平随着年龄增长逐渐升高,随后开始下降,但ECO组水平低于NECO组(均P0.05);RANKL水平随着年龄的增长逐渐升高,但ECO组水平低于NECO组,特别是在55岁后,ECO组RANKL水平明显低于NECO组(均P0.05)。ECO组和NECO组OPG/RANKL值分别在40～59岁和40～54岁时,随年龄增长逐渐升高,随后开始下降,且ECO组水平明显高于NECO组(均P0.05)。结论长期食用ECO可使广西壮族绝经后妇女体内雌激素和OPG保持在一定的水平,可防治绝经后骨质疏松。     

老年男性骨质疏松性髋部骨折患者血清网膜素-1与骨转换的关系

目的研究老年男性骨质疏松(OP)性髋部骨折患者血清网膜素(Omentin)-1水平与骨转换的关系。方法采用酶联免疫法测定82例老年男性OP性髋部骨折患者(OP骨折组)、50例老年男性OP患者(OP组)和50例正常男性老年人(对照组)血清Omentin-1、血清核因子(NF)-κB受体活化因子配体(RANKL)、骨保护素(OPG)水平,采用电化学发光免疫分析法测定其血清Ⅰ型胶原氨基端前肽(PINP)、β-胶原降解产物(CTX),采用双能X线骨密度仪分别测定其正位腰椎(L2～4)及左侧股骨颈骨密度(BMD)。分析老年男性OP性髋部骨折患者血清Omentin-1水平与骨转换指标间的关系。结果 OP骨折组腰椎股骨颈BMD、血清Omentin-1、OPG、PINP水平较OP组明显降低(均P0.01),血清RANKL、β-CTX水平、RANKL/OPG比值OP骨折组较OP组明显升高(均P0.01)。OP骨折组血清Omentin-1与腰椎、股骨颈BMD、血清OPG、PINP呈正相关(r=0.402,r=0.389,r=0.428,r=0.401,均P0.01),血清Omentin-1与RANKL、β-CTX、RANKL/OPG比值呈负相关(r=-0.447,r=-0.412,r=-0.528,均P0.01)。结论血清Omentin-1水平影响骨转换,血清Omentin-1水平降低在老年男性OP性髋部骨折的发病中发挥重要作用。血清Omentin-1、OPG、RA NKL、PINP、β-CTX水平可作为预测老年男性OP性骨折风险的参考指标。     

补肾活血方辅助治疗对绝经后骨质疏松患者炎性因子及骨代谢指标的影响

目的探讨补肾活血方辅助治疗对绝经后骨质疏松患者血清炎性因子及骨代谢指标的影响。方法选择118例绝经后骨质疏松患者为研究对象,根据住院时间分为试验组61例、对照组57例。对照组给予戊酸雌二醇与黄体醇胶囊治疗,试验组联合应用补肾活血方辅助治疗。治疗3个月经周期,比较两组中医证候疗效、血清炎性因子、骨代谢指标、不良反应等。结果治疗3个月后试验组中医证候积分明显低于对照组(P0.01),中医证候有效率明显高于对照组(P0.05);血清白细胞介素(IL)-6、C反应蛋白(CRP)、肿瘤坏死因子(TNF)-α均明显低于对照组,IL-10明显高于对照组(P0.05,P0.01);碱性磷酸酶(ALP)、骨钙蛋白(BGP)、骨保护素(OPG)均明显高于对照组,N端骨钙素(N-MID)明显低于对照组(P0.05,P0.01);口干、恶心、头痛等不良反应均明显低于对照组(P0.05)。结论补肾活血方辅助治疗有助于提高绝经后骨质疏松患者临床疗效,减少不良反应发生率,可能与拮抗炎症反应、调节骨代谢指标等因素有关。     

慢性阻塞性肺疾病并骨质疏松症患者血清RANKL、骨保护素水平的变化

目的 研究慢性阻塞性肺疾病(COPD)患者骨质疏松患病情况及OPG/RANK/RANKL系统在COPD骨代谢中的作用。方法 选取2020年1月～2021年4月于我院就诊的稳定期慢性阻塞性肺疾病患者及按2∶1比例随机纳入同期健康体检者为研究对象。应用双能X线骨密度仪(DEXA)测定腰椎L1～L4及股骨颈的骨密度(BMD),根据骨密度将稳定期COPD患者分为骨质疏松组和非骨质疏松组,检测所有研究对象肺功能及入组当天血清核因子κB受体活化因子配体(RANKL)、骨保护素(OPG)水平并进行统计学分析。结果 (1) COPD并发骨质疏松患病率为45.0%;(2) COPD骨质疏松组患者腰椎及股骨颈BMD随肺功能的下降而逐渐减低;(3) COPD骨质疏松组RANKL/OPG比值及血清RANKL水平明显高于非骨质疏松组,但OPG水平差异不显著。COPD骨质疏松组患者血清RANKL水平、RANKL/OPG比值随肺功能的下降而逐渐升高;(4)腰椎及股骨颈BMD与血清RANKL水平、RANKL/OPG比值呈负相关,与FEV₁(%)呈正相关,但与OPG水平无相关性。结论 慢性阻塞性肺...     

绝经后老年骨质疏松患者血清脂联素与骨代谢生化指标的相关性

目的探讨绝经后老年骨质疏松患者血清脂联素(ADP)与骨代谢生化指标的相关性及其发病机制。方法测定112例绝经后老年骨质疏松患者(实验组)和60例绝经后健康老年妇女(对照组)的血清APP、血清骨钙素(BGP)、骨特异性碱性磷酸酶(BAP)、抗酒石酸酸性磷酸酶-5b(TRACP-5b)、25羟基维他命D(25-OH-VD)和骨密度(BMD)等指标。结果实验组与对照组比较,各个检查部位BMD均有显著差异(均P0.05)。实验组血清ADP、BGP、BAP显著高于对照组(P0.05),而TRACP-5b和25-OH-VD显著低于对照组(P0.05)。绝经后老年骨质疏松患者的血清ADP与BGP、BAP呈显著正相关(r=0.658,0.573,均P0.01),与髋部BMD、腰椎BMD呈显著负相关(r=-0.476,-0.391,P0.01,P0.05)。绝经后健康老年妇女的血清ADP与髋部BMD、腰椎BMD呈显著负相关(r=-0.327,-0.425,均P0.05)。结论血清ADP水平与骨代谢生化指标密切相关,可能成为反映骨代谢状态的新型预测因子。     

妇女绝经前后骨代谢生化指标与心功能的相关性

目的探讨妇女绝经前后骨代谢生化指标与心功能的相关性。方法选择绝经前后妇女205例,按是否绝经分为2组,绝经前组100例,年龄30~49岁;绝经组105例,年龄50~65岁。用酶联免疫吸附法(ELISA)测定骨形成与骨吸收指标,同时测定心功能。结果与绝经前组比较,绝经组骨代谢生化指标显著增高(P0.05),射血分数(EF)显著降低(P0.05),心输出量(CO)、每搏输出量(SV)和二尖瓣E峰速度(MVVE)有降低趋势,但无统计学差异(P0.05)。结论对于绝经期妇女,心血管疾病与骨质疏松相互关联相互影响,测定骨代谢指标有助于评估发生心血管疾病的发生风险,评估心功能则有助于预测将来发生骨折的危险程度。     

绝经后妇女护骨素基因G1181C多态性与骨密度变化相关

目的　寻找护骨素基因(OPG)外显子中的单核苷酸多态性 (SNP),并分析其与绝经后妇女骨密度的关系。方法　在 205名绝经后妇女中,采用PCR和直接测序法确定OPG基因的SNP及基因型。应用双能X线骨密度仪测定腰椎和股骨颈骨密度 (BMD)。同时检测血清骨钙素 (BGP)、尿Ⅰ型胶原交联N端肽(NTx),以及血清护骨素(OPG)和核因子κB受体活化子配体 (RANKL)。结果　在OPG基因第一外显子中发现一个G1181C的SNP,该SNP的基因型频率分布依次为GG型占 0. 566、GC型 0. 346、CC型0. 088。去除年龄和体重的影响后,CC型的腰椎BMD明显高于GC和GG型 (P<0. 05),多元回归分析提示OPG基因型与绝经后妇女腰椎、股骨颈BMD相关 (P<0. 01)。Logistic回归分析显示OPG基因是绝经后妇女发生骨量减少和骨质疏松的独立危险因子,GG型发生骨量减少和骨质疏松的危险是CC型的 2. 83倍(P<0. 05)。结论　OPG基因的G1181C多态性与绝经后妇女BMD存在一定的关联,CC型对绝经后妇女腰椎BMD具有保护作用。     

血清胰岛素样生长因子Ⅰ与健康妇女护骨素、RANKL以及骨量的关系

目的研究血清胰岛素样生长因子Ⅰ（IGF—Ⅰ）和健康女性护骨素（OPG）、核因子κB受体活化子配体（RANKL）、以及骨量之间的关系。方法504名健康女性参加本研究，采用双能X线骨密度仪测定腰椎和股骨颈骨密度，同时测定血清IGF—Ⅰ、OPG、RANKL水平。结果在健康妇女中，血清IGF-Ⅰ水平与年龄呈明显的负相关（r=-0．702，P〈0．01），血清IGF—Ⅰ与OPG（r=-0．24，P〈0．01）、OPG／RANKL比值（r=-0．15，P〈0．01）呈明显的负相关，而与RANKL呈正相关（r=0．12，P〈0．05）。校正年龄因素的影响后，IGF-Ⅰ与健康妇女骨密度之间不存在相关性。在绝经后妇女中，骨质疏松组的IGF-Ⅰ水平低于正常组（P=0．056），但OPG、RANKL和OPG／RANKL比值两组间无明显差异。在IGF-Ⅰ五分位组比较中，最高IGF-Ⅰ组的OPG明显低于最低IGF-Ⅰ组，RANKL则无明显差异，多元回归结果显示停经和血清IGF-Ⅰ水平是影响健康女性骨量变化的主要因素。结论血清IGF-Ⅰ水平与健康妇女骨密度之间的关系受年龄的影响，IGF-Ⅰ作为偶联因子在骨重建中的作用（骨吸收）可能是由OPG-RANKL系统介导的。     

Serum osteoprotegerin and its ligand in cirrhotic patients referred for orthotopic liver transplantation: relationship with metabolic bone disease.

AIMS: A prospective study was carried out in 22 cirrhotic patients referred for orthotopic liver transplantation, in order to analyze serum osteoprotegerin (OPG) and RANKL levels and their relationship with metabolic bone disease. METHODS: Serum levels of OPG and RANKL were measured in all patients as well as bone markers, serum parathyroid hormone and 25-hydroxyvitamin D levels. OPG and RANKL values were compared with those obtained in 29 healthy controls. Bone mineral density (BMD) of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry and spinal X-rays were obtained to assess vertebral fractures. RESULTS: Serum OPG levels were higher in cirrhotic patients than in controls (6.4+/-2 vs 2.7+/-0.7 pmol/l; P=0.001) and RANKL serum levels were lower in cirrhotic patients (0.215+/-0.6 vs 1.012+/-1.2 pmol/l; P=0.002), with an increased OPG:RANKL ratio when compared with the control group (280.3+/-334.5 vs 113+/-137.6; P=0.04). Ten patients had osteoporosis (45%) and up to 45% skeletal fractures. No differences were found in OPG levels between patients with and without osteoporosis by densitometric criteria or fractures. Negative correlations were found between OPG levels and femoral neck (R-0.46; P=0.03) and total hip BMD (R-0.48; P=0.025). By contrast, OPG values were not related to markers of bone turnover. CONCLUSIONS: OPG values are elevated in cirrhotic patients before liver transplantation, particularly in those with low bone mass at the proximal femur.     

Increased formation of 8-iso-prostaglandin F(2alpha) is associated with altered bone metabolism and lower bone mass in hypercholesterolaemic subjects

OBJECTIVES: To investigate the relationship of 8-iso-prostaglandin (PG) F(2alpha) levels, a reliable marker of in vivo oxidative stress and lipid peroxidation, with bone mineral density (BMD), bone turnover markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in hypercholesterolaemia. DESIGN: Cross-sectional study. SETTING: University hospital centre. METHODS: Serum 8-iso-PGF(2alpha) levels were measured in 173 hypercholesterolaemic subjects and in 152 age- and sex-matched normocholesterolaemic controls. Femoral neck and lumbar spine BMD, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), OPG and RANKL levels, as well as urinary levels of C-terminal telopeptides of type I collagen (CTX-I), were also assessed. RESULTS: Hypercholesterolaemic subjects showed higher (P < 0.0001) serum 8-iso-PGF(2alpha) levels than controls. They also had decreased (P < 0.0001) femoral neck and lumbar spine BMD, and lower (P < 0.0001) serum BAP and OC levels. No significant differences between hypercholesterolaemic and control subjects were found when comparing urinary CTX-I levels, or serum OPG and RANKL levels. In multivariate linear regression analysis, serum 8-iso-PGF(2alpha) was the only negative predictor for femoral neck BMD and serum BAP and OC levels in hypercholesterolaemic subjects. No significant correlation (all P > 0.25) was present between serum 8-iso-PGF(2alpha) levels and urinary CTX-I levels, or serum OPG and RANKL levels, in hypercholesterolaemic subjects. CONCLUSIONS: We found an association between increased serum 8-iso-PGF(2alpha) levels and lower bone mass and reduced serum BAP and OC concentrations in hypercholesterolaemic subjects. These results would suggest a possible role for oxidative stress in the development of lower bone mass in hypercholesterolaemia.     

Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males

OBJECTIVE: Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF-kappaB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG-RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG-RANKL system and bone mineral metabolism in males. PATIENTS AND MEASUREMENTS: Serum concentrations of OPG, RANKL, oestradiol, total testosterone and IGF-I and bone mineral density (BMD) were measured in 80 Korean males aged 42-70 (mean age, 54.5 year). Enzyme-linked immunosorbent assays were used to determine the serum concentrations of OPG and RANKL. Serum concentrations of oestradiol, total testosterone, IGF-I and bone turnover markers were determined using standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. RESULTS: We observed a significant negative correlation between the serum OPG levels and lumbar spine BMD (r =-0.259, P < 0.05) in Spearman correlation analysis. Serum OPG levels and RANKL/OPG ratios were found to be significantly correlated to the serum osteocalcin levels (r =- 0.254, P < 0.05; r = 0.264, P < 0.05) in Spearman correlation analysis. Serum OPG levels were found to be negatively correlated with serum oestradiol levels (r =-0.319, P < 0.01) in Spearman correlation analysis. In addition, a significant positive correlation was found between serum RANKL/OPG ratios and oestradiol levels (r = 0.374, P < 0.001) in Spearman correlation analysis. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG levels or RANKL to OPG ratios in Spearman correlation analysis. In a multiple regression analysis, age, body mass index (BMI), and serum OPG levels were identified as a significant predictor for lumbar spine BMD, and age, BMI, serum OPG and RANKL levels for femoral neck BMD. In another multiple regression analysis, only serum oestradiol level was identified as a significant predictor for serum OPG or RANKL levels. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG or RANKL levels in multiple regression analysis. CONCLUSIONS: Our data show that the circulating OPG-RANKL system is associated with bone metabolism in the male populations. Also, our data suggest that OPG and RANKL may be mediators of the effects of oestradiol in male bone metabolism.     

The RANKL/OPG system and bone mineral density in patients with chronic liver disease

BACKGROUND/AIMS: Osteopenia and osteoporosis are common complications of chronic liver disease (CLD). Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate osteoclastogenesis and bone remodelling, and are involved in several inflammatory diseases. This study investigated the activation state of the RANKL/OPG system and its association with bone loss in CLD. METHODS: Serum levels of OPG and sRANKL were determined in 193 patients with CLD and 56 age- and gender-matched healthy controls. Cellular sources of OPG and RANKL were determined immunohistochemically. Dual-energy x-ray absorptiometry was performed to determine bone mineral density (BMD) of lumbar spine and femoral neck. RESULTS: sRANKL serum levels were significantly elevated in non-cirrhotic, but not cirrhotic patients compared to healthy controls. OPG serum levels were elevated 1.6-fold in non-cirrhotic and 2.8-fold in cirrhotic CLD patients. RANKL+ cells were mainly confined to portal fields, while OPG was broadly expressed. In the cirrhotic subgroup (87 patients) we observed a significantly higher OPG/sRANKL ratio in patients with osteopenia or osteoporosis of the lumbar spine and femoral neck region (T-score < -1) compared to those with normal BMD (T-score > or = -1). CONCLUSIONS: CLD is associated with alterations in RANKL/OPG serum levels, which could modulate bone loss in CLD.     

Age-related changes in cortical bone content of insulin-like growth factor binding protein (IGFBP)-3, IGFBP-5, osteoprotegerin,and calcium in postmenopausal osteoporosis: a cross-sectional study

Serum GH and IGF-I levels decline with increasing age, whereas osteoprotegerin (OPG) increases. IGFs as well as OPG are present in bone matrix and mediate the effects of many upstream hormones (e.g. estrogen). To evaluate whether changes in these proteins may to some extent explain the decrease in bone mass in postmenopausal or senile osteoporosis, we measured bone contents of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, and OPG in combined extracts obtained after EDTA and guanidine hydrochloride extraction in 60 postmenopausal women aged 47-74 (mean, 63) yr with a previous distal forearm fracture and a hip or spine Z-score less than 0. We found age-related increases in IGFBP-3 (r = 0.35; P < 0.01), IGFBP-5 (r = 0.59; P < 0.001), and OPG (r = 0.36; P < 0.01) in cortical bone, significantly inversely correlated with femoral neck and lumbar spine BMD. A correlation between age and OPG was also detected in trabecular bone (r = 0.27; P < 0.05). A pronounced age-related decrease in cortical calcium contents (r = -0.60; P < 0.001), positively correlated with femoral neck and lumbar spine BMD, was also found. No age-related changes were detected for IGF-I or IGF-II. The present study demonstrates age-related changes in cortical bone contents of IGFBPs, calcium, and OPG, possibly related to the pathophysiology of postmenopausal osteoporosis. As for OPG, our findings probably represent compensatory responses to increased osteoclastic resorption.     

Effects of the phytoestrogen genistein on the circulating soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin system in early postmenopausal women

We investigated the serum levels of both receptor activator of nuclear factor kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) in postmenopausal healthy women after a 1-yr therapy with genistein, (n = 30; 54 mg/d), hormone replacement therapy (n = 30; 1 mg/d 17beta-estradiol combined with norethisterone acetate) and placebo (n = 30). By comparison with placebo, the soluble RANKL (sRANKL)/OPG ratio was lower in the genistein group (-69 +/- 7%; P < 0.01 vs. placebo 81 +/- 24%) and in hormone replacement therapy-treated women (-11 +/- 2%; P < 0.01 vs. placebo). A positive correlation (r = 0.63; P < 0.01) was found between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in urinary deoxypyridinoline, a bone resorption marker. A negative correlation was observed between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in femoral neck bone mineral density (r = -0.7; P < 0.01). Our findings suggest that the sRANKL-OPG system may mediate the beneficial effects of genistein on bone remodeling in postmenopausal women.     

Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects

OBJECTIVE: Testosterone therapy for osteoporosis has not been studied extensively in women because of its potential to cause virilization. Female-to-male transsexuals are genetic females who suffer from gender dysphoria and thus take supra-physiologic doses of testosterone to change from the female to male phenotype. The aim of this study is to examine the effects of testosterone treatment on the genetic female skeleton. PATIENTS AND DESIGN: A group of 15 female-to-male transsexuals was prospectively enrolled for observation over a 2-year period. The subjects had a mean age of 37.0 +/- 3.0 years. All of the subjects self-administered testosterone esters intramuscularly at a mean dose of 70.7 +/- 4.5 mg weekly. MEASUREMENTS: The subjects had measurements of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) of the femoral neck and spine (L2-L4) at 12-month intervals. They had determinations of serum oestradiol, testosterone, soluble RANKL (sRANKL), osteoprotegerin (OPG) and urine N-telopeptide (NTX) at the date of enrolment and at the end of 2 years. results There was a significant positive increase in mean BMD of 7.8% at the femoral neck and a nonsignificant increase in mean BMD of 3.1% at the spine over 2 years. The levels of testosterone reached the upper normal range for males and the levels of oestradiol declined to near the postmenopausal range. sRANKL levels decreased significantly in female-to-male transsexuals who newly initiated testosterone therapy. There was no significant change in urine NTX or serum OPG during the study. CONCLUSIONS: We conclude that supra-physiologic testosterone therapy increases BMD at the hip while maintaining BMD at the spine in female-to-male transsexuals. The effects of testosterone may be the result of testosterone hormone directly acting on the bone or indirectly through aromatization to oestradiol. Lower RANKL levels coupled with unchanged OPG levels results in an increased OPG/RANKL ratio, which may be beneficial to the bone by inhibiting osteoclastogenesis.     

The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone

OBJECTIVE: Oestrogen replacement reduces the increased rate of bone remodelling after the menopause. Osteoprotegerin (OPG) is a negative regulator of osteoclast-mediated bone resorption. In vitro studies have shown that oestrogen stimulates OPG production. However, the role of OPG in physiological bone remodelling and its regulation by oestrogen in vivo remain controversial. In this study, we analysed the association between changes in serum OPG levels and bone turnover status before and after hormone therapy (HT) in healthy postmenopausal women. PATIENTS AND MEASUREMENTS: Ninety-nine healthy postmenopausal women of Korean ethnicity, aged 42-64 years (52.3 +/- 4.9 years, mean +/- SD) were enrolled in our study. Serum OPG levels were assessed by a highly sensitive sandwich-type enzyme immunoassay. Serum concentrations of osteocalcin (OC) and carboxyterminal telopeptides (CTx) were determined by electrochemiluminescence immunoassays. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Baseline levels of OPG correlated neither a the bone formation marker, serum OC, nor with a bone resorption marker, serum CTx. No significant association of baseline OPG was found with baseline BMD measured at the lumbar spine and femoral neck. Serum OPG levels measured after 3 months and 1 year of HT decreased significantly compared to baseline (P < 0.001 in both). The changes in circulating OPG at 3 months of HT correlated with the changes in both serum OC (r = 0.226, P = 0.029) and serum CTx (r = 0.214, P = 0.038) at 3 months after HT. However, there was no significant association between the changes in circulating OPG after 3 months of HT and BMD values of the lumbar spine or femoral neck after 1 year of HT. CONCLUSIONS: Our results suggest that baseline OPG levels do not reflect bone turnover status and that serial measurements of serum OPG after HT are not a useful predictor of the long-term effects of oestrogen on bone density. The decrease in serum concentrations of OPG after HT may occur to compensate for the action of oestrogen in suppressing bone resorption.