Changes in plasma bone GLA protein during treatment of bone disease

Summary Bone Gla protein (BGP) was measured in the plasma by radioimmunoassay (RIA) during treatment of 59 patients with bone diseases including Paget's disease (N=9), primary hyperparathyroidism (N=25), chronic renal failure (N=20), and cancer involving bone (N=5). Plasma BGP was increased above normal in all patients. BGP decreased in the patients with Paget's disease following the acute and chronic administration of salmon calcitonin. Plasma BGP was higher in women then in men with primary hyperparathyroidism. Following parathyroidectomy, BGP decreased in both sexes but the decrease was significant in women only. Plasma BGP was increased in patients with renal osteodystrophy and did not change after hemodialysis. In the patients with bone cancer, plasma BGP decreased during treatment of the attendant hypercalcemia with salmon calcitonin. Although plasma BGP and serum alkaline phosphatase (AP) levels were generally correlated in these studies, there were examples of dissociation between the two. The measurement of plasma BGP appears to provide a specific index of bone metabolism that may in some circumstances be more sensitive than serum alkaline phosphatase measurement. However, further studies are necessary to establish the clinical value of plasma BGP measurement by RIA in the management of patients with bone diseases.     

Serum markers of bone formation in parenteral nutrition patients

Summary Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r=0.24, p=NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r=0.81,P<0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r=0.89,P<0.01, n=11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r=0.60,P=0.05, n=11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful.     

原发性骨质疏松症患者骨密度和骨代谢指标的对比研究

目的探讨骨密度（BMD）和骨代谢指标在原发性骨质疏松症的诊治过程中的临床意义.方法采用XR-36型双能X线骨密度仪和放射免疫方法,对252例中老年志愿者不同部位的BMD及血清骨钙素（BGP）、Ⅰ型前胶原氨基端前肽、Ⅰ型胶原交联羧基末端肽的含量进行测定.结果①无论是对照组还是骨质疏松组（OP）,老年男性BMD均明显高于老年女性BMD,其差异具有非常显著性（P＜0.01）;②OP组的BGP值明显低于对照组,其差异具有显著性（P＜0.05）;OP组的血清Ⅰ型前胶原氨基端前肽（PINP）值均明显低于对照组,而血清Ⅰ型胶原交联羧基末端肽（ICTP）值均明显高于对照组,其差异具有显著性（P＜0.05）.结论联合检测BGP、HNP和ICTP水平可直接反映骨胶原合成和降解状态,对于判断老年OP的进程以及指导OP的用药有着重要的意义.     

Characteristics of biochemical markers for bone formation in the elderly

Currently, several promising biochemical markers for bone metabolism have been postulated and expected to be applied to their clinical use. Among these markers, circulating levels of bone Gla-protein (BGP) and carboxyterminal peptide of type I procollagen (P1CP) have been established as non-invasive indices to assess bone turnover, especially bone formation. We investigated age-related effects on serum levels of both peptides and relationships between loss of bone mass and biochemical indices in the elderly. Fasting blood sample were obtained from 330 healthy volunteers to simultaneously measure serum BGP, serum P1CP and serum tartrate-resistant acid phosphatase (TRACP) as a marker for bone resorption. Serum BGP levels were found almost stable throughout life in men with a tendency to decrease in the elderly. Serum P1CP levels linearly decreased towards 50 to 60 years of age in men, followed by its constant increase with aging afterwards. Although a constant increase in serum P1CP levels were noted in women with aging, serum BGP levels were found remarkably elevated during menopausal periods of 50 to 70 years of age, followed by its wide distribution in the elderly. Both serum BGP and P1CP levels were elevated accompanied with age-related decrease in glomerular filtration rates in the elderly. In addition, a bone specific index, TRACP/BGP ratio consolidated the negative correlation between serum TRACP and % changes of bone mineral density (BMD). However, TRACP/P1CP ratio had nothing to do with % change of BMD. In conclusion, loss of bone mass could be predicted by bone specific indices, particularly in elderly women with widely distributed bone turnover. The data in this paper were reported in part in International Coference on Osteoporosis, Kobe, November 1991.     

分娩前母血、脐血、新生儿血骨代谢相关激素水平及其意义

目的　测定新生儿血清骨代谢激素水平及探讨其临床意义。方法　采用放射免疫与免疫放射分析法测定８９ 例新生儿脐带血清,２２ 例出生３ 天婴儿血清骨钙素（ＢＧＰ）、降钙素（ｈ－ＣＴ）和甲状旁腺素（ｉＰＴＨ）水平。结果　新生儿脐带血ＢＧＰ、ｈ－ＣＴ 和 ｉＰＴＨ 水平分别为 １９．３±１６．８ μｇ／Ｌ、７８．９±５１．５ ｎｇ／Ｌ 和０．２２±０．１６ ｐｍ ｏｌ／Ｌ（ｘ±ｓ）,与分娩前母血比较,差异非常显著,Ｐ 值分别为Ｐ＜０．０１、Ｐ＜ ０．０１ 和Ｐ＜ ０．０１;出生３ 天婴儿血清ＢＧＰ、ｈ－ＣＴ 和ｉＰＴＨ 水平分别为７．４±２．３ μｇ／Ｌ、５７．８±１３．８ ｎｇ／Ｌ和５．６±１．６９ ｐｍ ｏｌ／Ｌ（ｘ±ｓ）,与新生儿脐带血比较差异非常显著,Ｐ 值分别为Ｐ＜ ０．０１、Ｐ＜ ０．０１ 和Ｐ＜ ０．０１。结论　本研究结果表明新生儿骨代谢激素的放射免疫测定是研究新生儿骨代谢变化的重要检测手段。     

阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的临床研究

目的观察阿仑膦酸钠对甲状腺功能减患者骨密度及骨生化、代谢影响的影响。方法初次诊断为未绝经的甲状腺功能减退女性患者64例,按随机数字表法将其分为治疗组32例,对照组32例。对照组给予左旋甲状腺素替代治疗,治疗组在对照组治疗的基础上给予阿仑膦酸钠70 mg/周,为期12个月。测定治疗不同时间段患者,腰椎1-4(L_(1-4))、左侧股骨颈BMD及血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3、碱性磷酸酶(ALP)、血清Ⅰ型胶原羧基端吡啶并啉交联肽(ICTP)以及血清骨钙蛋白(bone gla-protein,BGP)水平的变化情况。结果治疗前两组患者的骨密度及骨生化、代谢指标比较不具有统计学意义(P0.05);治疗12个月后,治疗组患者的腰椎1-4(L_(1-4))及股骨颈BMD均显著高于治疗前及同时期对照组(P0.05);治疗后12个月后,两组患者的血ALP、ICTP及BGP均有不同程度升高,治疗组的BGP升高程度明显大于对照组;而对照组的ALP及ICTP升高程度明显大于治疗组,比较有统计学意义(P0.05)。治疗前后两组患者血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3比较无明显差异(P0.05)。结论阿仑膦酸钠可以明显提升甲状腺功能减患者骨密度,改善骨生化和代谢状态。     

The dichotomy in the effects of 1,25 dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 on bone γ-carboxyglutamic acid-containing protein in serum and bone in vitamin D-deficient rats

Summary Vitamin D-deficient, second generation, rachitic rats showed significant decrease in bone Gla protein (BGP) levels in circulation and in the skeleton. 1,25 dehydroxyvitamin D₃ (1,25 (OH)₂D₃) exhibited the most potent influence on serum BGP levels in a dose-dependent manner. At a dose 25 ng/100 g body weight 1,25 (OH)₂D₃ showed a cumulative effect, i.e., the longer the treatment, the more circulating BGP was detected 24,25 dehydroxyvitamin D₃ (24,25(OH)₂D₃) at the same doses did not show similar effect on the serum BGP levels, regardless of the serum calcium levels. Bone BGP levels assayed at various sites representing endochondral and intramenbranous ossification demonstrated an opposite pattern. 1,25(OH)₂D₃ administration was not sufficient to restore bone BGP levels to normalcy, whereas in animals treated with 24,25(OH)₂D₃ bone BGP and calcium levels were significantly higher than control (Vitamin D₃-repleted) levels. The present results can be explained by the dual action of 1,25 (OH)₂D₃ on both synthesis and release of BGP by bone turnover, whereas 24,25 (OH)₂D₃ stimulates synthesis and accumulation of BGP in bone. These observations imply that caution is required in the interpretation of clinical data based solely on serum BGP determination.     

Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis

Summary Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E₂), estrone (E₁), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm³). Serum BGP correlated positively with CT scan (r+0.647,P<0.001). CT and age were negatively correlated (r−0.661,P<0.001) while CT and E₂ showed a positive correlation (r+0.554,P<0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r−0.421,P<0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis.     

甲状腺功能异常患者血生化、骨代谢及骨密度特点的临床研究

目的观察甲状腺功能减退症及甲状腺功能亢进症对骨密度以及骨代谢相关指标的影响。方法纳入甲状腺功能减退症女性37例为甲减组,甲状腺功能亢进症女性41例为甲亢组,健康体检女性人员40例为对照组。观察3组甲状腺功能指标血游离三碘甲状腺原氨酸(FT_3)、游离甲状腺激素(FT_4)和高敏感促甲状腺激素(TSH);骨代谢指标血Ca~(2+)、血P~(3+)、1,25-(OH)_2D_3、甲状旁腺激素(PTH)、碱性磷酸酶(ALP)、血清Ⅰ型胶原羧基端吡啶并啉交联肽(ICTP)以及血清骨钙蛋白(BGP)以及左侧股骨颈、正位腰椎1-4(L_(1-4))的骨密度情况。结果甲亢组血清FT_3、FT_4、ALP、BGP、ICTP水平高于对照组(P0.05),甲亢组血清TSH水平低于对照组(P0.05)。甲减组血清TSH水平高于对照组(P0.05),而血清FT_3、FT_4、ALP、BGP、ICTP水平显著低于对照组(P0.05)。甲亢及甲减组L1-4及左股骨颈骨密度显著低于对照组(P0.05)。3组受试者PTH、CT、Ca~(2+)、P~(3+)、1,25-(OH)_2D_3比较无统计学意义(P0.05)。结论甲亢及甲减都可以引起骨量丢失,骨密度降低;主要通过影响骨转化来实现的;应该重视甲状腺功能异常引起的骨密度及骨代谢异常。     

Serum bone GLA protein in streak gonad syndrome

Summary Osteoporosis is one of the most common complications of streak gonad syndrome (SGS), however its pathogenesis is still unclear. Bone Gla protein (BGP) has been found to be a serum marker of bone turnover in various metabolic disease states. In the present study serum BGP and alkaline phosphatase (AP) were measured in 13 osteoporotic patients with SGS and in 56 healthy women. Mean (±SD) serum BGP levels were normal (7.5±2.0 ng/ml) in seven patients who had been on estrogen-progestin replacement therapy and became significantly elevated (P<0.001) 2 and 3 months after discontinuation of the treatment (15.3±2.3 and 13.2±1.0 ng/ml, respectively). Mean (±SD) serum AP (207±65 U/l) showed significant increases (P<0.05) 2 months after withdrawal of hormonal substitution (287±74 U/l). Mean (±SD) serum BGP (15.4±3.5) and AP (287±49) levels were significantly higher (P<0.001 and <0.05, respectively) in six patients with SGS who had not been on hormonal substitution. These findings are consistent with those obtained in postmenopausal women suffering from “high remodelling osteoporosis” and suggest that bone turnover in osteoporotic patients with SGS is increased and the skeletal loss is a consequence of accelerated bone loss rather than decreased bone formation.     

甲状腺疾病与骨钙素

目的 观察甲亢、甲减患者血清骨钙素（ＢＧＰ）含量,探讨甲状腺功能异常与骨代谢的关系。方法 测定４０例甲亢患者,２０例甲减患者血清ＢＧＰ及甲状腺激素含量,并与３０例正常对照组比较。结果 甲亢患者血清ＢＧＰ含量明显高于正常对照组（Ｐ〈０．０１）,甲减患者血清ＢＧＰ含量明显低于正常对照组（Ｐ〈０．０１）,ＢＧＰ的含量与甲状腺激素（ＦＴ３、ＦＴ４）显著正相关,与ｓＴＳＨ显著负相关,与性别无明显相关。结论     

Changes in plasma bone GLA protein during treatment of bone disease

Bone Gla protein (BGP) was measured in the plasma by radioimmunoassay (RIA) during treatment of 59 patients with bone diseases including Paget's disease (N = 9), primary hyperparathyroidism (N = 25), chronic renal failure (N = 20), and cancer involving bone (N = 5). Plasma BGP was increased above normal in all patients. BGP decreased in the patients with Paget's disease following the acute and chronic administration of salmon calcitonin. Plasma BGP was higher in women then in men with primary hyperparathyroidism. Following parathyroidectomy, BGP decreased in both sexes but the decrease was significant in women only. Plasma BGP was increased in patients with renal osteodystrophy and did not change after hemodialysis. In the patients with bone cancer, plasma BGP decreased during treatment of the attendant hypercalcemia with salmon calcitonin. Although plasma BGP and serum alkaline phosphatase (AP) levels were generally correlated in these studies, there were examples of dissociation between the two. The measurement of plasma BGP appears to provide a specific index of bone metabolism that may in some circumstances be more sensitive than serum alkaline phosphatase measurement. However, further studies are necessary to establish the clinical value of plasma BGP measurement by RIA in the management of patients with bone diseases.     

糖尿病患者血清BGP与骨密度变化的研究

本文应用放射免疫分析方法对60例正常人及74例糖尿病患者的血清BGP进行了测定，并就其与BMD、血Ca、P及AKP等进行比较分析。结果表明：糖尿病患者血清BGP明显降低，而血Ca、P及AKP仍在正常范围．血清BGP与BMD呈负相关。说明血清BGP测定与BMD一样可以作为骨质疏松、糖尿病等代谢性骨病诊断与研究的一种敏感指标。     

Effect of interferon α on calcium and bone metabolism in patients with chronic hepatitis

We investigated the changes of natural type of interferon-α (IFNα) on calcium and bone metabolism in patients with chronic hepatitis C. Natural IFNα was injected intramuscularly at daily doses of 6 million units for 2 weeks to 10 patients with chronic hepatitis caused by hepatitis C virus, and followed by 3-times-a-week administration for another 10 weeks. The markers for bone metabolism including serum bone-Gla protein (BGP) concentration and urinary excretion of pyridinolines (pyridinoline and deoxypyridinoline) were measured before and during the treatment. The twelve-week administration of IFNα reduced pyridinoline excretion from 39.7±13.3 (SD) pmol/μ mol · creatinine to 28.3±8.1 pmol/μ mol · creatinine (p<0.06), and that of deoxypyridinoline from 6.51±3.38 pmol/μ mol · creatinine to 3.91±2.07 pmol/μ mol · creatinine (p<0.01), although serum levels of BGP and parathyroid hormone (PTH) did not show any significant changes. The ratio of BGP/urinary pyridinoline increased from 0.098±0.074 to 0.198±0.093 at the end of 12th week (p<0.03), and that of BGP/deoxypyridinoline increased from 0.630±0.502 to 1.550±0.788 at 12th week (p<0.02). Serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) did not change significantly during the study. IFNα reduces bone resorption in contrast with insignificant effects on bone formation in patients with mild to moderate hepatitis. The effects on calcium and bone metabolism may give beneficial effects for patients with high turnover osteoporosis.     

7-84 parathyroid hormone fragments are proportionally increased with the severity of uremic hyperparathyroidism

AIMS: Recent progress in PTH assay has revealed that the intact PTH assay kit in current use does not differentiate between the truncated 7-84 PTH molecule and the 1-84 PTH molecule. In our series, we examined the effectiveness of a new PTH assay as a noninvasive method of evaluating severity of uremic hyperparathyroidism. METHODS AND MATERIALS: Two hundred and seventy hemodialysis (HD) patients recruited from three HD centers were included and divided into subgroups according to the conventional iPTH assay results. Pre-dialysis blood samples were collected and subjected to two different PTH assays: "intact" PTH assay (iPTH) and "whole" PTH (wPTH) assay. Two biochemical markers of bone remodeling were also examined. RESULTS: In all cases, PTH levels determined by the wPTH assay were in the average 32.3% lower than those determined by the iPTH assay. The difference of the results of the two PTH assay methods, which indicated the portion of 7-84 PTH fragments of the total PTH molecules measured with the iPTH assay, was gradually increased while the severity of uremic hyperparathyroidism increased. Biochemical markers of bone formation/resorption showed a similar change. CONCLUSION: The portion of the 7-84 PTH fragments and markers of increased bone turnover increased in proportion to the severity of uremic hyperparathyroidism. This finding disproves the hypothetical role of 7-84 PTH fragments alone as the noninvasive marker of low-turnover bone disease in HD patients.     

Effect of acute increases in bone matrix degradation on circulating levels of bone-Gla protein

Serum bone Gla-protein (BGP), also called osteocalcin, is a specific and sensitive measure of bone turnover in a variety of metabolic bone disorders. Although some BGP diffuses into the circulation after synthesis by osteoblasts, most is incorporated into bone matrix where it remains until bone is resorbed. Thus, serum BGP could reflect bone formation, bone resorption, or a combination of both. The relationship of serum BGP to the components of bone turnover was evaluated in 18 normal women (mean age 48 yr; range 30-70) who received a continuous 24-h intravenous infusion of the 1-34 synthetic fragment of bovine parathyroid hormone. Mean +/- SE for urinary hydroxyproline excretion, an index of bone resorption, increased (from 22.7 +/- 2.2 to 38.5 +/- 3.7 micrograms/100 ml glomerular filtrate [GF], p less than .001), whereas levels of serum alkaline phosphatase, an index of bone formation, were unchanged (from 20 +/- 1 to 20 +/- 1 U/liter, NS). Despite the increase in bone resorption, levels of serum BGP decreased (from 8.8 +/- 0.8 to 6.8 ng/dl, p less than .001). The data suggest that circulating levels of BGP are a measure of bone formation but, at least in subjects with normal renal function, not a measure of bone resorption. Presumably BGP in bone matrix is degraded during osteoclastic resorption into fragments that either are not recognized by an antiserum raised against the native molecule or are rapidly cleared from the circulation.     

Serum bone gla-protein in osteoporosis treated with 1α-hydroxyvitamin D3 for more than five years

It has been reported that 1,25-dihydroxyvitamin D₃ increases serum bone Gla-protein (BGP) in a short period in osteoporotic patients as well as in normal subjects. There have been, however, no reports on serum BGP in osteoporotic patients under long term treatment with 1α-hydroxyvitamin D₃. We measured serum BGP in 11 osteoporotic women treated with 1α-hydroxyvitamin D₃ and calcium for 5–12 years, 8.4 years on average. Bone mineral density of distal radius was assessed by single photon absorptiometry. Other biochemical parameters such as serum alkaline phosphatase, fasting urinary hydroxyproline/creatinine and calcium/creatinine were also measured. Serum BGP levels were 6.25±0.36ng/ml (mean±S.E.), being all within the normal range (6.2±3.86ng/ml). We found no significant correlation between serum BGP and other biochemical parameters. Significant correlation was found neither between serum BGP and period of treatment nor between serum BGP and bone mineral density. Our result that serum BGP is within the normal range in osteoporotic patients whose bone mineral density has been maintained by long-term treatment suggests the normal bone turnover in these patients.     

Changes in Bone and Calcium Metabolism Following Hip Fracture in Elderly Patients

Although hip fracture is one of the most common causes of acute immobilization in elderly patients, little is known about the influence of immobilization on changes in bone and calcium metabolism following this event. We therefore compared serum biochemical indices of bone and calcium metabolism in 20 elderly subjects with hip fracture with those measured in 20 healthy age-matched controls. Rankin scores, a measure of functional dependence with 0 representing independence and 5 representing total dependence, were assigned. We also examined serial changes in these biochemical indices from shortly following the fracture to the early recovery period. Ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-[OH]₂D) were measured. One week after the fracture, mean serum concentrations of calcium and ICTP were elevated in correspondence to degree of immobilization (mean Rankin score; 4.4), while serum concentrations of BGP, PTH, 25-OHD, and 1,25-[OH]₂D were depressed. Rankin score (mean: 4.4) correlated positively with ICTP and negatively with BGP at this time. At 2 months, calcium and ICTP elevation decreased and BGP, PTH and 1,25-[OH]₂D were less depressed, coinciding with a decline in Rankin score from 4.2 to 2.2. Indices were further improved at 3 months (mean Rankin score, 1.3), with calcium and BGP returning to normal. We concluded that increased bone resorption, and decreased bone formation, and hypercalcemia are present by 1 week following the hip fracture, and some resorption increase persists for at least 3 months. These changes could explain in part the high risk of another hip fracture. Received: 3 April 2000 / Accepted: 15 December 2000     

不同性别及年龄因素对原发性骨质疏松症骨代谢指标、血清骨保护素及骨密度影响的研究

目的 研究不同性别及年龄因素对原发性骨质疏松症骨代谢指标、血清骨保护素及骨密度的影响。方法 选择92例原发性骨质疏松症患者为研究对象,根据性别的不同,将本组92例患者分为男性组36例和女性组56例;根据年龄的不同,将92例患者按10岁为一年龄段分组,分为40~50岁组38例,50~60岁组27例,60~70岁组17例,＞70岁组10例。分别对不同性别、不同年龄组患者的骨代谢指标（BGP、ALP）、血清骨保护素（OPG）及骨密度（BMD）进行检测,统计分析不同性别、年龄阶段患者各指标水平的变化趋势。结果 男性组患者平均BGP、ALP、OPG指标水平均低于女性组（P均＜0.05）,平均腰椎正位、右股骨颈BMD均高于女性组（P均＜0.05）。随着患者年龄的增加, BGP、ALP、OPG指标水平逐渐升高（P＜0.05）;同时,随着患者年龄的增加,腰椎正位、右股骨颈BMD指标值逐渐下降（P＜0.05）。结论 性别及年龄是影响原发性骨质疏松症患者的骨代谢指标、血清骨保护素及骨密度指标水平的重要因素,通过其影响机制的分析可为该病的防控提供参考依据。     

Effect of etidronate disodium on bone turnover following surgical menopause

Summary A longitudinal study was performed to document the effect of surgical menopause and postmenopausal etidronate disodium therapy on several nonhistomorphometric indices of bone turnover. Twenty healthy, premenopausal women undergoing oophorectomy for nonmalignant conditions were studied preoperatively and at 3 monthly intervals postoperatively. Sequential measurements of serum calcium (Ca), alkaline phosphatase (AP), bone Gla protein (BGP), and urinary calcium and hydroxyproline excretion, expressed as a ratio of urinary creatinine (UCa/Cr and UOHp/Cr, respectively) were obtained. Twenty-four-hour whole body retention of diphosphonate (WBR) and radial bone density were also measured. When a postoperative increase in bone turnover was observed, patients were randomized to receive either 400 mg etidronate disodium daily or placebo for 3 months. Oophorectomy was associated with a significant increase in WBR, Ca, AP, and BGP and an insignificant rise in UCa/Cr. A variable pattern of UOHp/Cr was seen. Patients on placebo maintained these elevated levels of Ca, BGP, and UCa/Cr. WBR and AP continued to rise. Etidronate disodium therapy resulted in a fall towards premenopausal levels in WBR, Ca, and UCa/Cr. AP and BGP were unchanged. Three months after stopping etidronate, BGP fell significantly and the decrease in Ca was maintained; however, WBR and UCa/Cr had returned towards pretreatment values. Bone density measurements did not change significantly. An increase in several of the indices of bone turnover was seen following oophorectomy. Etidronate disodium suppressed this increase, affecting indices of both resorption and formation. This effect on formation may be an unavoidable consequence of normal resorption-formation coupling. The ability of etidronate alone to maintain postmenopausal bone mass has yet to be established. However, the suppressive effect of this diphosphonate on the accelerated bone turnover found after oophorectomy suggests that etidronate may have a potentially useful role as an inhibitor of resorption in a pulsed regimen.