Influence of nutritional status on serum large N-truncated PTH, but not PTH(1-84) in hemodialysis patients.

BACKGROUND: Serum level of parathyroid hormone (PTH), measured by second-generation intact PTH (I-PTH), is known to be associated with nutritional status in hemodialysis (HD) patients. We investigated whether PTH(7-84) and larger N-truncated PTH or PTH(1-84) might be affected by nutritional status in HD patients. METHODS: Serum PTH was determined in 170 male HD patients by either a Bio-intact PTH (Bio-PTH) or I-PTH assay. Lean body mass in the trunk region was measured as a nutritional marker by dual X-ray absorptiometry. RESULTS: The serum PTH(7-84) level was theoretically obtained from the difference between serum I-PTH and Bio-PTH because I-PTH assay cross-reacted with PTH(7-84) with the same degree as PTH(1-84), although N-truncated PTH fragment larger than PTH(7-84) might affect theoretical serum PTH(7-84) level, although slightly. Serum PTH(1-84) was directly obtained from the serum Bio-PTH value because of its exclusive reaction with PTH(1-84). Serum PTH(7-84) correlated significantly with nutritional markers such as body weight, albumin, protein catabolic rate (PCR), TACBUN, BUN, phosphate, and lean body mass in the trunk, whereas PTH(1-84) correlated only with phosphate. Multiple regression analysis revealed that PCR, body weight, and lean body mass in the trunk region are significant factors independently associated with PTH(7-84), but not with PTH(1-84). CONCLUSIONS: The results suggest that serum levels of PTH(7-84) and larger N-truncated PTH fragments, but not PTH(1-84), might be affected by the nutritional state in HD patients, which might explain the reported correlation of serum I-PTH levels with nutritional markers.     

Technical and clinical characterization of the Bio-PTH (1-84) immunochemiluminometric assay and comparison with a second-generation assay for parathyroid hormone

BACKGROUND: The Bio-Intact parathyroid hormone (1-84) assay (Bio-PTH), a newly developed two-site immunochemiluminometric assay, measures exclusively PTH (1-84) in contrast to second-generation "intact PTH" (I-PTH) assays. We investigated the technical performance and clinical significance of this new assay. METHODS: PTH was measured simultaneously by the Bio-PTH assay and Allegro intact PTH IRMA in sera from Japanese patients with calcium disorders. RESULTS: Measured Bio-PTH in serum was unaffected by six freeze-thaw cycles and was stable at 4 degrees C for 7 days and during storage at -20 or -80 degrees C over 28 days. The calibration curve was linear to 1800 ng/L. The detection limit was 3.9 ng/L. The intra- and interassay imprecision was <2.8% and 3.5%, respectively, for analyte concentrations spanning the range of the calibration curve. Bio-PTH was unaffected by a 1000-fold excess of PTH (7-84), although I-PTH reacted equally with PTH (7-84) and PTH (1-84). Bio-PTH was correlated with I-PTH in healthy individuals (r = 0.953; P <0.0001; n = 26) and in the full population without renal dysfunction (r = 0.994; P <0.0001; n = 62). In 72 volunteers, mean (SD) Bio-PTH was 22.2 (7.1) ng/L, or 62% of the mean I-PTH [36.1 (22.3) ng/L]. This ratio was 51% in hemodialysis patients (n = 177). Mean Bio-PTH was high in patients with primary hyperparathyroidism [121 (85) ng/L; n = 18] and hemodialysis patients [102 (104) ng/L; n = 177], low in idiopathic hypoparathyroidism [5.5 (2.8) ng/L; n = 4], and within 2 SD of the mean for healthy controls in Paget disease of the bone [34 (15) ng/L; n = 9] and bone metastasis [24 (12) ng/L; n = 8]. CONCLUSION: The Bio-PTH assay is sensitive and precise and produces expected results for patients with the studied disorders of calcium metabolism.     

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.     

Serum concentrations of cross-linked N-telopeptides of type I collagen: new marker for bone resorption in hemodialysis patients

BACKGROUND: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). METHODS: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (beta-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient's bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. RESULTS: Serum NTX correlated significantly with beta-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as beta-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, beta-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. CONCLUSION: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.     

Association between increased serum osteoprotegerin levels and improvement in bone mineral density after parathyroidectomy in hemodialysis patients

Secondary hyperparathyroidism (SHPT) is a common complication in chronic renal disease. Osteoprotegerin (OPG), an extracellular cytokine receptor secreted by osteoblasts, can promote bone formation by inhibiting the function of osteoclasts. Hemodialysis (HD) patients have elevated serum OPG levels. OPG secretion can be suppressed with high parathyroid hormone (PTH) levels. HD patients with refractory SHPT can benefit from parathyroidectomy (PTX) treatment, but the changes of serum OPG, bone turnover markers and bone mineral density (BMD) following PTX in HD patients remain unclear. In this study, patients on maintenance HD who received PTX for refractory SHPT (n = 28) were prospectively followed for 1 year. Serum intact PTH (iPTH), alkaline phosphatase (Alk-P), and OPG were measured serially; BMD was measured pre-PTX and at 1 year after PTX. After PTX, serum iPTH levels reduced profoundly. Serum Alk-P levels increased rapidly, peaking at 2 weeks post-PTX, while serum OPG levels gradually increased at 2 weeks after PTX and peaked at 2 months. BMD improved in both femoral neck (FN; cancellous and cortical bone) and lumbar spine (LS; cancellous bone). Higher baseline iPTH levels were associated with greater FN and LS BMD improvements at one year after PTX. The increment of serum OPG was correlated with the increase in LS BMD, implying that inhibition of osteoclastic bone resorption may improve BMD within the first year after PTX. These findings suggest that PTX removes the suppressive effects of high PTH on OPG secretion, resulting in the increased serum OPG levels that may contribute to BMD improvement.     

Serum N-terminal midfragment vs. intact osteocalcin immunoradiometric assay as markers for bone turnover and bone loss in hemodialysis patients.

Although labile, assay of intact osteocalcin (iOC) is established as the standard assay for evaluating osteoblastic function. The present study examines the clinical usefulness of the newly developed immunoradiometric assay for osteocalcin (OC), which identifies the stable N-terminal midfragment of OC (N-MID OC assay), in hemodialysis (HD) patients. The performance of N-MID OC assay was compared to that of iOC assay in the sera obtained from 137 male HD patients, by comparing these assays with those of other bone metabolic markers and bone loss during a 1-year period before determination of serum markers. Serum N-MID OC values did not decrease significantly during 24 h incubation at room temperature, whereas serum iOC decreased significantly after 1 h incubation. Serum N-MID and iOC in the 137 male HD patients were 197.3 +/- 57.8 and 34.6 +/- 30.0 ng/ml, respectively, or 3.9 +/- 3.1 and 2.8 +/- 2.4 times above the respective reported normal upper limits. Serum N-MID OC correlated significantly in a positive manner with serum iOC (r = 0.934, P < 0.0001). Serum N-MID OC correlated no less significantly in a positive manner with serum levels of bone alkaline phosphatase, deoxypyridinoline, and intact parathyroid hormone compared to serum iOC. Of interest was the fact that serum N-MID OC, but not iOC, correlated significantly with both the amount and the rate of bone loss at the distal radius 1/3. In summary, the findings suggest that N-MID OC immunoreactivity is much more stable than iOC immunoreactivity and that N-MID OC assay may be less susceptible to the OC fragments reported to accumulate in uremic serum. It may, therefore, prove more reliable than iOC assay for evaluating bone turnover, and thus for reflecting bone loss, in HD patients.     

甲状腺功能亢进患者治疗前和治疗早期骨代谢参数的改变 关于甲状腺功能亢进患者骨吸收骨形成研究的结果对指导临床治疗的意义

目的了解甲状腺功能亢进(甲亢)患者治疗前和治疗早期骨矿物质代谢的变化,探讨其对骨代谢参数改变的影响机制。方法选择42例甲亢治疗前和治疗早期患者,采用放射免疫法测定了血清骨钙素(BGP)、I型胶原羧基末端肽(ICTP)、甲状旁腺素(PTH-M)及相关生化指标,并与32例健康对照者进行比较。结果甲亢治疗前血碱性磷酸酶(AKP)、骨钙素(BGP)、I型胶原羧基末端肽(ICTP)均值显著高于对照组(P<0.001)。治疗后血AKP、BGP显著下降(P<0.001)其均值仍高于对照组(P<0.05)。ICTP明显低于治疗前(P<0.001)与对照组比较差异无显著(P>0.05)。相关分析显示,血BGP与ICTP正相关,血TT3与BGP、AKP、ICTP呈正相关,血sTSH与BGP、ICTP呈负相关。结论甲亢治疗前过量甲状腺激素加速骨转换,以破骨细胞活动占优势,使骨吸收显著大于骨形成,是甲亢骨病主要原因,甲亢治疗早期,骨吸收快速降低,骨形成仍高,以成骨细胞活动占优势,有利于骨重建。     

An automated 'bio-intact' PTH assay: a step towards standardisation and improved correlation with parathyroid function in renal disease

BACKGROUND: Most methods for the determination of parathyroid hormone (PTH) show cross-reactivity with N-truncated forms of PTH. The analytic and diagnostic value of a recently developed automated PTH test without this cross-reactivity was examined. METHODS: The PTH levels of 73 patients undergoing hemodialysis were compared using the 'bio-intact' PTH (Nichols Institute Diagnostics) and 3 'intact' PTH tests (from Nichols, Roche Elecsys and Diagnostics Corporation DPC). Further, the (non 1-84) PTH fragment and the PTH ratio (bio-intact PTH/(non 1-84) PTH) were calculated. All results were then correlated with biochemical bone markers (bone-specific alkaline phosphatase and bone collagen C-terminal telopeptides in serum). RESULTS: 'Bio-intact' PTH values were lower than the PTH results generated by the 'intact' PTH assays. Results of all PTH tests were closely correlated (r=0.96-0.98, p<0.01). Correlations with biochemical bone markers were high (r=0.31-0.63, p<0.01), but no significant association between the PTH ratio and all other tests (r=-0.2 to 0.03) was found. CONCLUSIONS: In stable hemodialysis patients, the different PTH tests show a similar correlation with the bone markers. It is however desirable to measure PTH with assays devoid of any cross-reaction for a better comparability. In this study, the PTH ratio was not correlated with biochemical bone markers; the use of this ratio requires further investigation.     

Two-site assay of intact parathyroid hormone in primary hyperparathyroidism: studies in basal conditions, following adenoma removal and during calcium and EDTA infusion

This study has been carried out in order to investigate parathyroid hormone secretion in patients with primary hyperparathyroidism in basal conditions, during stimulation and suppression tests and following successful surgery. Parathyroid gland secretory activity has been evaluated by a highly sensitive immunoradiometric assay (IRMA) which detects only the biologically intact active hormone and with a well established midmolecule (MM) PTH RIA. There was a good correlation between the two assays in basal state (r = 0.779); however the correlation found between serum PTH levels and total calcium values was better for the intact hormone (P < 0.001) than for the radioimmunoassay (P < 0.05). Twenty-four hours following surgery, serum intact PTH levels were in all patients < 10 pg/ml while midmolecule PTH was still detectable, thereafter remaining at a higher level during the next six days. Serum IRMA PTH levels fell rapidly in response to the increase in serum calcium, then there was a trend to reach a plateau; serum midregion PTH levels fell, although slower than those of intact hormone. The percent increase obtained for serum intact hormone levels was higher than that observed for MM RIA, following EDTA stimulation. The results obtained indicate that the assays of intact and midmolecule parathyroid hormone clearly reflect different aspects of hormone metabolism ‘in vivo’ and may prove therefore to be useful for its investigation in various calcium disorders.     

Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH) detected by intact PTH assays

BACKGROUND: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. METHODS: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL. min(-1). 1.73 m(-2), 12 with a GFR between 30 and 60 mL. min(-1). 1.73 m(-2), and 8 with a GFR between 5 and 30 mL. min(-1). 1.73 m(-2). We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups. RESULTS: Only patients with a GFR <30 mL. min(-1). 1.73 m(-2) and hemodialyzed patients had decreased Ca(2+) and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca(2+) (r = -0.66; P <0.0001), CrCl (r = -0.61; P <0.001), 1,25-dihydroxyvitamin D (r = -0.40; P <0.05), and 25-hydroxyvitamin D (r = -0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the composition of I-PTH increased with each GFR decrease, being 21% in healthy individuals, 32% in progressive renal failure patients with a GFR <30 mL. min(-1). 1.73 m(-2), and 50% in hemodialyzed patients, with PTH(1-84) making up the difference. CONCLUSIONS: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is <30 mL. min(-1). 1.73 m(-2). Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of renal failure.     

Calcium loss in sweat does not stimulate PTH release: A study of Bikram hot yoga

It has been hypothesized that sweat loss during exercise causes a disruption in calcium homeostasis that activates bone resorption and over time leads to low bone mineral density. The purpose of this small pilot study was to determine whether dermal calcium loss from a bout of excessive sweating during light intensity physical activity triggers an increase in biomarkers of bone resorption. Biochemical markers related to bone homeostasis were measured before and after a 90 min Bikram hot yoga practice performed in a room heated to 105 °F with 40 % humidity. Participants were five females with a mean age of 47.4 ± 4.7 years. Nude body weight, serum total calcium (Ca²⁺), free ionized calcium, albumin, parathyroid hormone (PTH) and CTX-I were measured before and after a Bikram hot yoga practice. Mean estimated sweat loss was 1.54 ± 0.65 L, which elicited a 1.9 ± 0.9 % decrease in participant’s body weight. Mean Ca²⁺ concentration in sweat was 2.9 ± 1.7 mg/dl and the estimated mean total calcium lost was 41.3 ± 16.4 mg. Serum ionized Ca²⁺ increased from 4.76 ± 0.29 mg/dl to 5.35 ± 0.36 mg/dl after the Bikram hot yoga practice (p = 0.0118). Serum PTH decreased from pre- 33.9 ± 3.3 pg/ml to post- 29.9 ± 2.1 pg/ml yoga practice (p = 0.0015) when adjusted for hemoconcentration (PTH_ADJ), implying a decrease in PTH secretion. We conclude that calcium loss in sweat during 90 min of Bikram hot yoga did not trigger an increase in PTH secretion and did not initiate bone resorption.     

血液透析患者血清瘦素水平与骨密度和骨代谢的关系研究

目的观察血液透析患者体内血清瘦素水平与骨密度、骨代谢指标之间的关系。方法94名血液透析患者均采用双能X射线骨密度仪检测计算股骨颈和腰椎骨的骨密度。采用酶联免疫法测定血清瘦素,放射免疫检定法测定甲状旁腺素（PTH）,酶联免疫吸附法测定Ⅰ型胶原羧基端肽β特殊序列（β-CTX）,采用全自动生化分析仪检测骨特异性碱性磷酸酶（BAP）。结果女性患者的血清瘦素明显高于男性患者（t=2.44,P＜0.05）,且女性患者血清瘦素和PTH、β-CTX、BAP均呈负相关（r分别=-0.58、-0.23、-0.37,P均＜0.05）,男性患者血清瘦素和PTH、β-CTX呈负相关（r分别=-0.41、-0.45,P均＜0.05）。所有患者的血清瘦素与骨密度相关性不明显（r分别=0.06、0.06,P均＞0.05）。结论血液透析患者女性的血清瘦素水平明显高于男性,女性患者血清瘦素与骨代谢呈负相关;男性患者中血清瘦素与骨代谢中的骨吸收负相关,而与骨形成无关。所有患者的血清瘦素与骨密度相关性均不明显。     

An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis.

Female patients (n = 20) with osteoporosis, aged 66 +/- 5 yr were studied during a 24-h infusion of parathyroid hormone (PTH [1-34]) at a rate of 0.5 IU equivalents/kg.h, and then during a 28-d period of subcutaneous injections, at a dose of 800 IU equivalents per day. Thereafter half the patients received subcutaneous injections of calcitonin, 75 U/d for 42 d, and all patients were followed to the end of a 90-d cycle. Biochemical markers of bone formation (serum alkaline phosphatase, osteocalcin, and the carboxy-terminal extension peptide of pro-collagen 1) and bone resorption (fasting urine calcium, hydroxyproline, and deoxypyridinoline) were compared during treatment by the intravenous and subcutaneous route of PTH administration, and subsequently during calcitonin therapy. During intravenous PTH infusion there were significant reductions in all three bone formation markers, despite expected rises in urinary calcium and hydroxyproline. By contrast, the circulating markers of bone formation increased rapidly by > 100% of baseline values during daily PTH injections (P < 0.001). Significant increases in bone resorption markers were only seen at the end of the 28 d of injections, but were < 100% over baseline values, (P < 0.05). Quantitative bone histomorphometry from biopsies obtained after 28 d of PTH treatment confirmed that bone formation at both the cellular and tissue levels were two to five times higher than similar indices measured in a control group of biopsies from untreated osteoporotic women. Subsequent treatment of these patients with calcitonin showed no significant changes in the biochemical markers of bone formation and only a modest attenuation of bone resorption. Thus, PTH infusion may inhibit bone formation, as judged by circulating biochemical markers, whereas daily injections confirm the potent anabolic actions of the hormone. Sequential calcitonin therapy does not appear to act synergistically with PTH in cyclical therapeutic protocols.     

老年男性2型糖尿病患者甲状旁腺素、维生素D与骨密度的关系

目的 探讨老年男性2型糖尿病患者主要钙调激素甲状旁腺素(PTH)和维生素D的变化对骨密度的影响.方法 应用双能X线骨密度仪测定60例老年男性2型糖尿病患者的腰椎和髋部骨密度,检测血清中骨代谢及血糖相关的指标,并根据骨密度测定结果将60例老年男性2型糖尿病患者分为骨量减少组(32例)、骨质疏松组(12例)、正常组(16例),测定3组的血清PTH和25羟维生素D3,分析其与患者不同部位骨密度的相关性.结果 依据患者腰椎或髋部的骨密度值,骨质疏松的检出率为20.0％(12/60),骨量减少的检出率为53.3％(32/60).3组的血清PTH比较差异有统计学意义(F=3.32,P=0.043),骨量减少组、骨质疏松组与正常组相比,PTH水平明显上升[(44.87±10.62)、(50.24±20.32)μg/L与(36.96±12.36)μg/L,P均＜0.05].但25羟维生素D3浓度3组比较差异无统计学意义(P＞0.05).相关分析显示,PTH水平与髋部骨矿面密度(BMD)呈显著负相关(r=-0.224,P ＜0.05),与腰椎BMD无显著相关性(r=-0.187,P＞0.05).结论 老年男性2型糖尿病患者的髋部BMD与血清PTH浓度负相关.     

High bone turnover in the elderly.

OBJECTIVES: To document lifestyle-associated variations in biochemical markers of bone metabolism in advanced age. STUDY DESIGN: Cross-sectional study. SETTING: Department of Geriatrics, University Hospital, Basel, Switzerland. SUBJECTS: Three hundred twelve ambulatory and 193 institutionalized men and women, aged 54 to 99 yrs. OUTCOME MEASUREMENTS: Biochemical markers of bone resorption (urinary deoxypyridinolin and N-telopeptides), serum vitamin D metabolites, and serum intact parathyroid hormone (iPTH) concentrations were assessed. Mean values of all parameters were correlated with a six-grade activity score. Physical activity score reflected the degree of weight bearing, ranging from walking independently to primarily bed-bound. Ambulatory subjects were measured in summertime and institutionalized subjects in wintertime to accentuate seasonality of vitamin D hormone levels. RESULTS: Excretion of bone resorption markers was significantly higher in the institutionalized and physically inactive patients compared with those who were ambulatory and physically active (p = .0001). Vitamin D deficiency (25-hydroxyvitamin D of <12 ng/mL) was present in 86% of institutionalized and 15% of ambulatory subjects, and 1,25-dihydroxyvitamin D serum concentrations were lower in institutionalized than in ambulatory subjects (p = .0001). Mean serum concentrations for iPTH were similar for both the institutionalized and ambulatory groups. When subjects were arranged according to activity score, mean excretion of urinary bone resorption markers increased with degree of inactivity. CONCLUSION: Despite the difference in vitamin D metabolites, iPTH serum concentrations did not differ significantly between the institutionalized and ambulatory groups. However, institutionalized and physically inactive participants had markedly elevated excretion of urinary bone resorption markers compared with ambulatory and physically active subjects. These results suggest that high bone turnover in the elderly may be caused by physical inactivity related to low mechanical loading rather than secondary hyperparathyroidism.     

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients

Abstract. Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of ‘type II’ osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca⁺⁺), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d^-1) and/or calcium (1g d^-1) were subsequently prospectively evaluated. Despite low (mean 11·6 nmol l^-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)₂D) were mostly normal. Neither correlated with Ca⁺⁺ or PTH. PTH correlated negatively not only with Ca⁺⁺ (r=–0·328, P < 0·05) but also with ICTP (r=–0·306, P < 0·05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca⁺⁺ (r=–0·268, P= 0·06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)₂D and slightly decreased PTH. Ca⁺⁺ values were normal and remained stable. In conclusion, Ca⁺⁺ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to ‘type II’ secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.     

老年2型糖尿病骨代谢的研究

目的　了解老年人 2型糖尿病骨代谢的现状及影响骨代谢的有关因素 ,对 2型糖尿病并发骨质疏松作出早期诊断和治疗。方法　用QCT法分别测定男女糖尿病及非糖尿病患者的骨密度 (BMD) ,用放免法检测骨钙素 (BGP)及Ⅰ型胶原羧基端肽 (ICTP)、甲状旁腺激素 (PTH)等指标。结果　男女糖尿病患者BMD及BGP均低于非糖尿病者 ,而ICTP及PTH均高于非糖尿病者 ,BMD与糖尿病病程、ICTP、PTH、血糖呈显著负相关。结论　糖尿病患者存在BMD显著下降 ,其骨代谢特点是骨吸收增加 ,骨形成降低。血糖控制不良是糖尿病并发骨质疏松的危险因素之一。     

Circulating levels of osteoprotegerin and receptor activator of NF-kappaB ligand in patients with chronic renal failure.

BACKGROUND: Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of nuclear factor-kappaB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. The aim of this study was to investigate the relationship between the OPG-RANKL system and bone mineral metabolism in patients with chronic renal failure (CRF). METHODS: Serum OPG, RANKL, osteocalcin, cross-linked c-telopeptide of type I collagen (ICTP), intact parathyroid hormone (PTH), bone alkaline phosphatase and cystatin C levels were measured in 40 chronic hemodialysis male patients and 32 age- and sex-matched healthy controls. Their lumbar spine bone mineral density (LS-BMD) was measured by dual energy X-ray absorptiometry. RESULTS: Serum OPG, RANKL, PTH, bone alkaline phosphatase and cystatin C levels were significantly increased in patients with CRF. Serum OPG was positively correlated to serum RANKL and cystatin C. Positive correlations were found between serum RANKL and cystatin C and ICTP. LS-BMD was significantly lower in patients with CRF than in controls. In patients with CRF, LS-BMD was inversely correlated to serum RANKL and cystatin C, whereas it was positively correlated to serum OPG. CONCLUSIONS: The OPG-RANKL system is involved in the pathogenesis and regulation of bone turnover in CRF. Circulating levels of OPG and RANKL may be useful markers to assess turnover renal osteopathies.     

绝经后骨质疏松症患者血清几丁质酶壳三糖苷酶、血管活性肠肽水平与骨密度及骨代谢标志物的相关性研究

目的　探讨绝经后骨质疏松症（postmenopausal osteoporosis, PMOP） 患者血清几丁质酶壳三糖苷酶1（Chitortiosidase 1, CHIT1）,血管活性肠肽（vasoactive intestinal peptide, VIP）水平与骨密度及骨代谢标志物的相关性。方法　纳入厦门大学附属东南医院2017 年12 月～ 2020 年12 月收治的PMOP 患者60 例为PMOP 组,取同期于医院体检的绝经后妇女60 例为对照组,比较两组血清CHIT1 和VIP 水平、腰椎L1-4 和股骨颈的骨密度、甲状旁腺素（parathyroid hormone, PTH）、I 型羧基端交联端肽胶原（type I collage cross-linked-telopeptide, CTX）和I 型前胶原氨基端前肽（procollagen I N-terminal peptide, PINP）水平,分析上述指标的相关性,观察PMOP 发生的影响因素。结果　PMOP 组血清CHIT1（9.64±2.25）,CTX（0.52±0.13mg/L）,PINP（60.84±23.51 mg/L） 水平高于对照组（5.83±1.26nmol/mol/h,0.25±0.07mg/L, 39.83±12.52mg/L）,血清VIP（161.32±27.86 pg/ml）,PTH（10.49±2.52pmol/L）水平以及腰椎L1-4（0.74±0.13g/cm2）,股骨颈的骨密度（0.62±0.0.14g/cm2）低于对照组（302.61±43.92pg/ml,15.19±4.64pmol/L,1.19±0.16g/cm2,0.88±0.12g/cm2）, 差异均有统计学意义（t=6.110 ～ 21.042,均P=0.000）。PMOP 患者血清CHIT1 水平与血清PTH,腰椎L1-4,股骨颈的骨密度呈负相关（r=-0.327,-0.479,-0.485,均P ＜ 0.05）,与血清CTX,PINP 水平呈正相关（r=0.482,0.423,均P ＜ 0.05）,血清VIP 水平与血清PTH,腰椎L1-4,股骨颈的骨密度呈正相关（r=0.515,0.482,0.535,均P=0.000）,与血清CTX,PINP 水平呈负相关（r= -0.414,-0.386,均P ＜ 0.05）。Logistic 回归分析提示,CHIT1 ＞ 7.73nmol/mol/h 是PMOP 发生的危险因素,而VIP ＞ 231.97pg/ml,腰椎L1-4 骨密度＞ 0.97g/cm? 是预防PMOP 发生的保护性因素（P ＜ 0.05）。结论　PMOP 患者血清CHIT1 水平增高,而VIP 水平降低,且二者均与腰椎L1-4,股骨颈骨密度以及骨代谢标志物有相关性,临床有望将二者作为评估PMOP 病情的辅助指标。