Optimizing results from pQCT: reliability of operator-dependent pQCT variables in cadavers and humans with low bone mass.

Peripheral quantitative computed tomography (pQCT) can assess bone geometric properties and separate cortical from trabecular bone. Despite pQCT's potential benefits for research, most reliability and accuracy studies have used a constant acquisition and analysis protocol. There are, however, numerous steps in the pQCT scan acquisition and analysis that are operator dependent. Whether or not these influence the quality of the pQCT scans and, potentially, the precision and validity of the data collected has been little explored. We investigated how pQCT outputs changed when operator-dependent parameters were varied, particularly when the bone of interest was of low mineral density. We found that bone parameters and scan failure rate varied significantly depending on the acquisition resolution; only one scan slice at the 10 and 30% radius is required to maintain adequate precision, and reference lines for sites should use a reproducible landmark. These results provide a foundation for recommending scan acquisition and analysis options for patients with low bone mass.     

Effects of strontium ranelate on bone mass and bone turnover in women with thalassemia major-related osteoporosis

Subjects affected by thalassemia major (TM) often have reduced bone mass and increased fracture risk. Strontium ranelate (SrR) is an effective treatment for postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone-specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1), sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was measured by visual analog scale (VAS) every 6 months. After 24 months, TM women treated with SrR had increased their spine BMD values in comparison to baseline (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05); however, no significant changes were observed in the placebo group. In the SrR group, a reduction of back pain was observed after 18 months in comparison to baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our study reports for the first time the effects of SrR in the treatment of TM-related osteoporosis. SrR treatment improved BMD and normalized bone turnover markers, as well as lowering sclerostin serum levels.     

Hypovitaminosis D, impaired bone turnover and low bone mass are common in patients with peripheral arterial disease

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6±4.6 ng/ml, P<0.0001) as compared to PAD II stages and controls (19.0±7.6 and 19.1±9.1 ng/ml), paralleled by lower serum calcium [2.24±0.02 mmol/l, P=0.0002 versus PAD II (2.36±0.02) and P<0.0001 versus controls (2.39±0.02)] and higher iPTH serum levels (66.3±3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3±3.5) and healthy controls (38.5±2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.S. Kudlacek represents the Austrian Study Group on Normative Values of Bone Metabolism.     

氧化应激和骨代谢水平与类风湿关节炎合并低骨量的相互关系

目的探讨RA患者体内AOPP水平和骨代谢标志物的变化,明确其与RA患者低骨量间的关系。方法收集RA患者70例,50例正常人作为对照组,检测两组BMD、AOPP、SOD、β-CTX和t PINP水平。再根据BMD值将RA患者分组OP组、骨量正常组和骨量减少组,分析各检测指标与骨量减少的相关性。结果 RA组腰椎BMD值和T值均低于正常组(P0.05)。RA组AOPP、β-CTX水平较正常组显著升高(P0.05),SOD、t PINP水平较正常人显著降低(P0.05)。在RA患者中OP组与骨量正常组和骨量减少组相比,病程长,DAS28评分高,AOPP、β-CTX水平也明显增高(P0.05),但在年龄、激素的服用率及DMARD服用率的比较上,OP组与另两组相比无差异(P0.05)。线性回归方程分析发现,β-CTX、t PINP、AOPP、DAS28、病程、SOD、糖皮质激素服用情况可能均与骨量减少的发生相关(P0.10),进一步采用多因素Logistic Regression回归分析后发现,β-CTX、AOPP、DAS28、病程为RA患者合并骨量下降的危险因素。结论 RA患者与正常人比骨量下降明显,骨质疏松的发生率高,其中病程、疾病活动及体内的氧化应激水平与骨量减少的发生相关,在制定RA的治疗方案时,可监测患者体内氧化应激和骨代谢水平的改变,必要时加用抗氧化剂治疗。     

Establishing a reference range for bone turnover markers in young, healthy women

INTRODUCTION: Biochemical markers of bone turnover (BTMs) are important in determining fracture risk in postmenopausal women; high levels being associated with increased risk. A proposed goal of anti-resorptive therapy is to reduce BTMs to the lower half of the reference range for healthy young pre-menopausal women. Our aims were a) to establish reference ranges for bone alkaline phosphatase (bone ALP), crosslinked C- and N-telopeptides of type I collagen (betaCTX, NTX), osteocalcin (OC) and procollagen type I N propeptide (PINP) in pre-menopausal women and b) to investigate the determinants of these BTMs. METHODS: BTMs were measured in peripheral blood and second morning void urine collected from 200 healthy pre-menopausal women ages 30 to 45 years. Each subject completed a short medical and lifestyle questionnaire. RESULTS: BTMs were higher before the age of 35 years than after it. BTMs were higher in women with low BMI (betaCTX and OC), low alcohol consumption (PINP), current smoking habit (bone ALP and NTX), and around time of ovulation (NTX). CONCLUSIONS: We recommend that the age range 35 to 45 years should be used when establishing BTM reference ranges in women.     

Leptin and biochemical markers of bone turnover in dialysis patients

BACKGROUND AND OBJECTIVE: The adipose tissue cytokine leptin is suggested to interfere with bone turnover mechanisms because, in rats with leptin deficiency, intra-cerebroventricular administration of this cytokine causes a reduction in bone mass. We studied the relationship between plasma leptin and biochemical bone turnover indicators in 161 hemodialysis (HD) patients. RESULTS: Plasma leptin was sex-dependent, being significantly higher (p<0.001 ) in female dialysis patients than in male dialysis patients, and it related directly to body mass index (BMI). In males, plasma leptin related inversely to serum intact parathyroid (PTH) (partial r= -0.34), serum PTH(1-84) (r= -0.36), carboxyterminal PTH (C-PTH) fragment (r= -0.31) and serum PTH(1-84)/C-PTH fragment ratio (r= -0.22), while no such relationships were found in females. Of 93 male dialysis patients, 44 had a serum intact PTH <100 pg/mL and 14 had a serum PTH(1-84)/C-PTH fragment ratio <1. In a multiple logistic regression analysis in males, for each 1 ng/mL increase in plasma leptin there was an 11% excess risk of serum intact PTH <100 pg/mL (odds ratio (OR) 1.11, 95% confidence interval (95% CI): 1.02-1.20, p=0.01) and a similar OR was found when low bone turnover was defined based on a serum PTH(1-84)/C-PTH fragment ratio <1 (p=0.01). In addition, plasma leptin related inversely to skeletal alkaline phosphatase and again this relationship was found in male but not in female dialysis patients. CONCLUSIONS: Our data support the theory that leptin reduces bone turnover in male dialysis patients. Whether this link underlies a noxious or a protective mechanism, i.e. if it can serve to limit high bone turnover due to hyperparathyroidism, remains to be established in prospective studies based on solid outcome measures like the risk of fractures.     

Indoxyl sulfate exacerbates low bone turnover induced by parathyroidectomy in young adult rats

Low-turnover bone disease is one of the bone abnormalities observed in patients with chronic kidney disease (CKD) and is recognized to be associated with low serum parathyroid hormone (PTH) level and skeletal resistance to PTH. Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood as renal dysfunction progresses in CKD patients. A recent in vitro study using an osteoblastic cell culture system suggests that IS has an important role in the pathogenesis of low bone turnover through induction of skeletal resistance to PTH. However, the effects of IS on the progression of low bone turnover have not been elucidated. In the present study, we produced rats with low bone turnover by performing parathyroidectomy (PTX) and fed these rats a diet containing indole, a precursor of IS, to elevate blood IS level from indole metabolism. Bone metabolism was evaluated by measuring histomorphometric parameters of secondary spongiosa of the femur. Histomorphometric analyses revealed significant decreases in both bone formation–related parameters and bone resorption–related parameters in PTX rats. In indole-treated PTX rats, further decreases in bone formation–related parameters were observed. In addition, serum alkaline phosphatase activity, a bone formation marker, and bone mineral density of the tibia tended to decrease in indole-treated PTX rats. These findings strongly suggest that IS exacerbates low bone turnover through inhibition of bone formation by mechanisms unrelated to skeletal resistance to PTH.     

Effects of arzoxifene on bone, lipid markers, and safety parameters in postmenopausal women with low bone mass

Summary  

In this Phase 2 study of postmenopausal women with low bone, arzoxifene (a selective estrogen receptor modulator (SERM)) significantly reduced bone turnover marker levels and increased bone mineral density (BMD) versus placebo. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene, a SERM in current clinical use. Arzoxifene’s safety profile appeared similar to raloxifene.     

Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis

Objective

We systematically assessed bone mineral density (BMD), bone turnover markers (BTM), and fractures in a large cohort of patients with Indolent Systemic Mastocytosis (ISM).

Methods

Eighty-two patients (mean age 48 years, 37 women) with ISM were studied. BMD was measured by dual X-ray absorptiometry at the lumbar spine and proximal hip. The serum markers of bone turnover included bone-specific alkaline phosphatase, C-telopeptides of type I collagen, and serum osteocalcin. Previous clinical fractures were registered and spine X-ray was obtained from all patients.

Results

Three women were excluded for concomitant diseases associated to osteoporosis. Osteoporosis according with the WHO classification (T-score < − 2.5) was found in 16 patients (20.0%) (7 females and 9 men). Mastocytosis-related low BMD (Z-score at either the spine or the hip < − 2) was found in 3 women (9%) and 13 men (28%). The BMD was generally lower at the spine than at the hip. No significant correlation was observed between serum tryptase levels and T or Z-score BMD. One or more moderate or severe vertebral fractures were found in 17 patients (12 men); in 11 of them Z-score values were > − 2 or not valuable at the spine. No significant difference was found in the prevalence of mastocytosis-related low BMD and/or vertebral fractures between patients with or without skin involvement. Two patients had radiographic and densitometric osteosclerosis-like characteristics. In osteoporotic patients higher, normal or lower serum BTM were found, without correlations with serum tryptase levels, while in patients with osteosclerosis both BTM and serum tryptase values were particularly increased.

Conclusions

Vertebral osteoporosis and fractures are frequent in patients with ISM. Spine X-ray and densitometric examination are warranted in all patients, also without skin involvement and particularly in males; Z-score other than T-score BMD must be evaluated. Patients with idiopathic osteoporosis should be evaluated for mast cell disease. Both high than low BTM can be observed in patients with osteoporosis while osteosclerosis is characterized by high bone turnover and serum tryptase levels.     

Biochemical markers of bone turnover in patients with localized and metastasized prostate cancer

OBJECTIVE: To evaluate and compare the value of several markers of bone turnover in different stages of prostate cancer, as bone metastases are a common feature in this disease, and for assessing bone metastases both bone formation and bone resorption markers are diagnostic. PATIENTS AND METHODS: The prospective study included 219 men, i.e. 129 undergoing radical retropubic prostatectomy (RRP) and 25 with bone metastases due to prostate cancer, and 65 with benign urological disorders who served as controls. Before any treatment the concentrations of alkaline phosphatase (ALP), osteocalcin, serum C-terminal telopeptide of type I collagen (S-CTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were determined. RESULTS: Men undergoing RRP were divided into those with lymph node-negative, localized (pT3, 101) and lymph node-positive (28) disease, after histological examination. The controls had the lowest marker levels while patients with bone metastases due to prostate cancer had the highest levels, with significance for ALP, osteocalcin and TRACP5b. Patients with lymph node-positive cancer had significantly high serum levels of TRACP5b and ALP but not for osteocalcin and S-CTX. CONCLUSIONS: Bone turnover markers represent a new diagnostic tool in prostate cancer; the present data show that both bone resorption and bone formation are crucial for detecting bone metastases in prostate cancer. The value of bone turnover markers in high-risk patients should be evaluated in a longitudinal study.     

Monitoring Bone Growth Using Quantitative Ultrasound in Comparison with DXA and pQCT

Quantitative ultrasound (QUS) is a safe, inexpensive, and nonradiation method for bone density assessment. QUS correlates with, and predicts fragility fractures comparable to, dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) in postmenopausal women. However, its validity in monitoring bone growth in children is not well understood. Two hundred and fifty-eight 10–13 yr pubertal girls and 9 37–43 yr adults without diseases or history of medications known to affect bone metabolism were included in the 2-yr prospective study. Calcaneal broadband ultrasound attenuation (cBUA) was assessed using QUS-2 (Quidel, Santa Clara, CA), speed of sound of tibial shaft (tSOS) using Omnisense (Sunlight Technologies, Israel), apparent volumetric BMD (vBMD) of tibial shaft using peripheral quantitative computed tomography (pQCT; XCT2000, Stratec), and femoral neck (FN) and lumbar spine 2–4 (LS) areal BMD (aBMD) using DXA (Prodigy, GE). Over the 2 yr in girls, FN and LS aBMD showed the largest increases (17 ± 8% and 20 ± 8%, respectively), followed by tibial vBMD and cBUA (10 ± 5% and 9 ± 9%, respectively). There was no apparent change in tSOS (2 ± 3%). The increase in FN and LS aBMD attenuated 48% and 40%, respectively, after adjustment of the change in body size. The change of cBUA correlated significantly with change in tibial vBMD and FN and LS aBMD (r = 0.24–0.40). At the matched location, tSOS correlated only with cortical vBMD, not with cortical thickness, apparent vBMD, or bone size. The long-term reproducibility, assessed using the concordance correlation coefficient of young adults' pre-post measurements, was substantially lower in tSOS than cBUA, tibial vBMD, FN, and LS aBMD (0.65 vs 0.97, 0.95, 0.98, and 0.96; p < 0.05). The transverse transmission method-derived calcaneal BUA, but not the axial transmission method-derived SOS, is comparable to DXA and pQCT for monitoring bone densitometric change in pubertal girls. The role of QUS in fracture-risk prediction in children and adolescents needs further investigation.     

A longitudinal HR‐pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density,cortical and trabecular microarchitecture,biomechanics, and bone turnover

The goal of this study was to characterize longitudinal changes in bone microarchitecture and function in women treated with an established antifracture therapeutic. In this double‐blind, placebo‐controlled pilot study, 53 early postmenopausal women with low bone density (age = 56 ± 4 years; femoral neck T‐score = ?1.5 ± 0.6) were monitored by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) for 24 months following randomization to alendronate (ALN) or placebo (PBO) treatment groups. Subjects underwent annual HR‐pQCT imaging of the distal radius and tibia, dual‐energy X‐ray absorptiometry (DXA), and determination of biochemical markers of bone turnover (BSAP and uNTx). In addition to bone density and microarchitecture assessment, regional analysis, cortical porosity quantification, and micro‐finite‐element analysis were performed. After 24 months of treatment, at the distal tibia but not the radius, HR‐pQCT measures showed significant improvements over baseline in the ALN group, particularly densitometric measures in the cortical and trabecular compartments and endocortical geometry (cortical thickness and area, medullary area) (p < .05). Cortical volumetric bone mineral density (vBMD) in the tibia alone showed a significant difference between treatment groups after 24 months (p < .05); however, regionally, significant differences in Tb.vBMD, Tb.N, and Ct.Th were found for the lateral quadrant of the radius (p < .05). Spearman correlation analysis revealed that the biomechanical response to ALN in the radius and tibia was specifically associated with changes in trabecular microarchitecture (|ρ| = 0.51 to 0.80, p < .05), whereas PBO progression of bone loss was associated with a broad range of changes in density, geometry, and microarchitecture (|ρ| = 0.56 to 0.89, p < .05). Baseline cortical geometry and porosity measures best predicted ALN‐induced change in biomechanics at both sites (ρ > 0.48, p < .05). These findings suggest a more pronounced response to ALN in the tibia than in the radius, driven by trabecular and endocortical changes. © 2010 American Society for Bone and Mineral Research.     

绝经后腰痛女性骨密度及骨转换标志物与腰椎Modic改变的相关性研究

目的探讨绝经后慢性腰痛女性骨密度(BMD)及骨转换标志物(BTMs)与腰椎Modic改变的相关性。方法回顾性分析2017年1月至2019年12月因慢性腰痛伴或不伴下肢放射痛在本院就诊的200例绝经后女性患者,采用双能X线测定腰椎BMD;采用罗氏化学发光法测定空腹静脉血Ⅰ型原胶原N末端前肽(PINP)、Ⅰ型胶原C末端肽特殊序列(β-CTX)水平;通过MRI检查患者腰椎Modic改变情况;采用二分类Logistic回归分析患者BTMs与腰椎BMD和腰椎Modic改变的相关性。结果 200例绝经后慢性腰痛女性腰椎Modic改变发生率为51.5%,Modic改变患者腰椎BMD低于无Modic改变患者,二者差异具有统计学意义,而PINP和β-CTX水平高于无Modic改变患者,二者差异具有统计学意义(P0.05)。β-CTX和PINP与Modic改变呈正相关,关联具有统计学意义(P0.05),而腰椎BMD与Modic改变呈负相关,关联具有统计学意义(P0.05)。结论绝经后慢性腰痛女性腰椎BMD及BTMs与腰椎Modic改变有相关性;随着BTMs升高或者BMD降低,腰椎Modic改变的发生率升高,提示临床上应早期监测绝经后慢性腰痛女性BTMs和腰椎BMD的变化,早期给予抗骨质疏松治疗,为治疗绝经后女性腰椎Modic改变引起的背痛患者提供了新的思路。     

The use of micro-CT to evaluate cortical bone geometry and strength in nude rats: correlation with mechanical testing, pQCT and DXA

In both clinical and experimental settings, access to quantitative methods enabling the objective evaluation of cortical bone mass, structure, geometry and strength are essential for the assessment of efficacy and safety of different treatments aimed to improve bone strength. The ability of non-invasive methodologies (DXA, pQCT and micro-CT) to assess and quantify cortical bone mass and geometry was tested in a nude rat model in which bone loss was induced by surgical castration. Treatment with a bone antiresorptive (alendronate) or a bone forming (PTH) drug was used to: (A) validate the nude rat model in terms of bone metabolism, (B) test the ability of each technology to detect change in cortical bone geometry and (C) correlate cortical bone geometry with bone strength data obtained by 3-point bending method. Our observations regarding effect of castration and treatment with PTH and alendronate on cortical bone parameters in nude rats is in general agreement with previously published data obtained in immunocompetent male rats under similar experimental conditions. Data presented here support the hypothesis that nude rats have similar bone physiology and response to known bone therapies to that observed in normal rats and therefore could be effectively used to predict skeletal response in humans. All three technologies deployed in this study (DXA, pQCT and micro-CT) proved useful in describing cancellous and/or cortical bone parameters and positive correlations were demonstrated between data obtained by different methods. The cross-sectional area of a bone structure is crucial for resisting loads in bending or torsion and is described as "areal moment of inertia" for bending, and as "polar moment of inertia" in torsion. Novel, three-dimensional micro-CT methodology used in this study to assess geometry of cortical bone provides data that accurately describes cortical bone geometry and parallels cortical bone strength results obtained by the 3-point bending method. Our micro-CT data meet the criteria of providing quick, reproducible and accurate answers regarding cortical bone geometry as a predictor of cortical bone strength.     

2型糖尿病患者血清FGF21、骨连结蛋白和骨转换指标的相关性研究

目的测量患有2型糖尿病(type 2 diabetes mellitus,T2DM)的早期糖尿病肾病患者的骨转换标志物(bone turnover markers,BTM)水平,并研究BTM与血清成纤维细胞生长因子-21(FGF21)和骨粘连蛋白(OC)的关联。方法纳入患有T2DM的80例男性和150例女性,测量其临床特征、BTM、OC和FGF21水平。结果96例(41.7%)患者出现尿蛋白异常。异常尿蛋白组血清OC(P<0.05)和FGF21(P<0.05)水平明显高于正常尿蛋白组患者。异常尿蛋白组患者血清P1NP水平略低(P<0.05),但调整FBG、PBG和HbA1c后差异消失。血清FGF21水平与eGFR独立且负相关,但与uACR无关。而OC与uACR独立且正相关。血清FGF21水平与P1NP独立地呈负相关。结论持续的高血糖可能会抑制骨形成,OC和FGF21均与T2DM患者的早期肾病相关。     

原发性甲状旁腺机能亢进症手术治疗后骨量和骨代谢指标的变化

目的 了解甲状旁腺切除术对原发性甲状旁腺机能亢进症病人的骨矿密度及骨代谢指标变化的影响。方法 ４０例病人,其中３０例未治疗组（男：女＝３：２７）;１０例已手术治疗组（男：女＝３：７）,手术后时间１～２４月（平均５．３±７．９月）。用ＤＥＸＡ测量腰椎及股骨颈的骨矿密度,同时,测定血清中的甲状旁腺素（ＰＴＨ）,骨钙素（ＯＣ）,及骨唾液酸蛋白（ＢＳＰ）。结果 在已手术组病人其腰椎及股骨颈骨矿密度再没有明     

广场舞对绝经期后骨质疏松患者的骨密度和骨转换指标影响的研究

目的观察广场舞对绝经后骨质疏松患者的骨密度、骨转换指标的影响。方法研究组:口服钙尔奇D600 mg每日1次的同时,联合广场舞运动方法干预,每周5次,每次平均0.5~1.0小时;对照组:单纯采用口服钙尔奇D600 mg每日1次,观察两组实验前及实验干预6个月后受试者骨密度、骨转换指标变化、骨痛。结果 (1)骨密度变化:研究组治疗6个月后,腰椎L2-4、股骨颈部的骨密度较治疗前明显升高(P0.05),Ward’s区骨密度无显著性改变。而对照组各部位骨密度较前无明显改变(P0.05)。(2)血生化中血钙、血磷及碱性磷酸酶指标值:两组生化指标在治疗前后无统计学差异(P0.05);治疗6个月后P1NP的水平明显升高(P0.05),β-CTX水平未有明显改变(P0.05)。(3)疼痛程度改善情况:两组治疗前后疼痛分级比较,研究组疼痛明显改善。结论广场舞运动能部分改善绝经后妇女骨密度,并且可以缓解骨质疏松引起的疼痛,是一种切实可行的预防和治疗骨质疏松症的临床方案。