Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis

Summary Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05±1.27 ng/ml vs 4.83±0.88 ng/ml;p<0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.     

股骨头坏死愈胶囊对兔激素性股骨头坏死血清骨钙素与降钙素的影响

目的探讨股骨头坏死愈胶囊对激素性股骨头坏死的防治效果及作用机制,为该药的临床应用提供科学依据。方法以36只新西兰大白兔为研究对象,随机分为正常组和股骨头坏死愈组、通络生骨胶囊组、造模空白组,通过血液学检查统计各组血清中骨钙素及降钙素水平。结果通过光镜观察结合X线电子计算机断层扫描(CT)和核磁共振扫描(MRI)检查证明造模成功,治疗后,造模组血清BGP与CT水平明显低于正常组(P0.05);给药12周时测量结果显示股骨头坏死愈组血清BGP与CT水平明显高于模型组(P0.05);通络生骨胶囊组血清BGP与CT水平明显高于模型组(P0.05);股骨头坏死愈组血清BGP与CT水平与通络生骨胶囊组相比,各个指标差异均无统计学意义(P0.05)。结论股骨头坏死愈胶囊能够提高兔激素性股骨头坏死血清骨钙素与降钙素水平,对激素性股骨头坏死具有治疗作用。     

Effect of short-term hypomagnesemia on the chemical and mechanical properties of rat bone.

Magnesium is known to have an essential role in determining the properties of bone, but the way in which Mg exerts its actions remains unclear. Although long-term Mg deficiency is known to produce osteopenia, the effects of short-term Mg deficiency have not been established. To test the hypothesis that Mg deficiency results in an altered pattern of initial mineralization and concomitant altered bone properties, the radiographic, histologic, chemical, and mechanical properties of the bones of rats given a Mg-deficient diet were compared to those of rats pair-fed the same diet supplemented with Mg. Short-term Mg-deficiency in the diet of growing rats produced a significant decrease in both the trabecular bone volume and the mineral content of the newly formed metaphysis, a significant increase in the Ca:P ratio, and a slight, but significant increase in hydroxyapatite crystallite size and/or perfection in the metaphysis. Comparable, but not significant, trends were found in the diaphyses. Metaphyseal bone osteocalcin levels were reduced in the Mg-deficient rats and lipid was more easily extracted from their bones. No detectable alterations in radiographic microstructure were noted. Mechanically, a significant decrease in the maximum three-point bend strength of the femurs of Mg-deficient rats was observed. These data support the hypothesis that short-term Mg deficiency affects the pattern of bone mineral formation.     

Clinical Research of Acupuncture Therapy on Children with Cerebral Palsy

Objective To investigate the rationale of acupuncture therapy on children with cerebral palsy. Methods 70 children with cerebral palsy were involved. All of them received the acupuncture injection, The serum osteocalcin was measured in 16 children and the serum growth hormone was measured in 28 children before and after the therapy. The changes of cranial CT scan were also observed in 28 children. GMFM was used to evaluate the changes of gross motor functions. Results The serum growth hormone elevated in 82,1% children （23/28）, the serum osteocalcin decreased in 87.5% children （14/16） and CT appearance was variously improved in 60.7% children （17/28） after acupuncture therapy. The GMFM scores were significantly improved after the therapy （p〈0.05）. Conclusion The acupuncture therapy might regulate the hormone secretion by stimulating the acupuncture points and improve the growth and development of children with cerebral palsy.     

Increased bone resorption and decreased bone formation in Chinese patients with hip fracture

Biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (hydroxyproline excretion and bone isoenzyme of acid phosphatase) were measured in 30 patients (15 M and 15 F) with hip fracture and 30 healthy subjects matched for age and sex. Bone isoenzyme of tartrate-resistant acid phosphatase (TRACP) was measured by a recently developed specific immunoassay. Serum osteocalcin concentration and bone-specific alkaline phosphatase activity were significantly lower and serum TRACP concentration and urinary hydroxyproline excretion were elevated in patients compared with healthy subjects. We suggest that there is reduced bone formation and increased bone resorption in patients with hip fracture.     

Bone Turnover and Insulin-like Growth Factor I Levels Increase After Improved Glycemic Control in Noninsulin-dependent Diabetes Mellitus

It is unclear whether both bone resorption and formation are affected by glycemic control, and contribute to diabetic osteopenia. In this study, 20 patients with noninsulin-dependent diabetes mellitus (12 men and 8 postmenopausal women) and 20 healthy control subjects (10 men and 10 postmenopausal women) were examined at baseline and 2 months. The diabetic patients showed an improvement of glycemic control (decreased HbA_1c) at the second measurement. Analysis of variance showed that there was no effect of gender on the variables that increased with improved glycemic control, and therefore results are presented for both male and female subjects. Baseline values of serum osteocalcin, a marker of formation, were significantly lower in diabetic patients compared with healthy subjects (2.5 ± 1.3 versus 4.4 ± 1.4 ng/ml; P= 0.0006), but markers of bone resorption [urinary pyridinoline (PYD), deoxypyridinoline (DPD)] did not differ. Improved glycemic control in diabetic patients resulted in increased values of PYD (P= 0.012), DPD (P= 0.049), serum osteocalcin (P= 0.001), and serum insulin-like growth factor I (IGF-I, P= 0.003), but no change in serum parathyroid hormone or 25-hydroxyvitamin D. In diabetic patients there were inverse correlations for the percent change from baseline to improved glycemic control for osteocalcin and HbA_1c (r =−0.53; P= 0.016) and glucose (r =−0.46; P= 0.050). These data suggest that improved glycemic control is accompanied by an increase in bone turnover for male and female diabetic patients, possibly mediated by increased levels of circulating IGF-I. Received: 8 August 1997 / Accepted: 20 January 1998     

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling

Introduction In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. Patients and measurements In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5–20 years) and 55 adult women (age: 20–37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 β estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D₃]. Results Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567±895 vs. 8976±805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 β estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age subgroups of the AN patients. Other hormones or nutritional parameters displayed age-related correlations with bone markers, leading to different stepwise regression models for each age interval. In mature adolescent AN patients, up to 54% of the osteocalcin variance was due to BMI, cortisol and 17 β estradiol, while 54% of the sCTX variance was determined by GH. In adult subjects, freeT3 and IGF-I accounted for 64% of osteocalcin variance, while 65% of the sCTX variance was due to GH, FTI and methoxyamines. Conclusions We suggest a more complex mechanism of AN bone uncoupling that includes not only “classical” influence elements like cortisol, IGF-I, GH or 17 β estradiol but also freeT3, catecholamines and a “direct” hormone-independent impact of denutrition. Continuous changes of these influences with age should be considered within the therapeutic approach to AN bone loss.     

对长期低钙摄入幼鼠的骨骼的研究——Ⅲ 低钙时幼鼠的骨钙素水平

本文研究低钙摄入、维生素D供给正常时幼鼠血中骨钙素水平,以了解低钙时成骨细胞活性。实验采用60只21～23日Wistar断乳幼鼠,随机分为四组:A组,正常钙与VitD摄X组;B组,中度低钙组;C组,重度低钙组;D组,VitD缺乏组。定期监测血25-(OH)D_3水平。于实验中期(3周),末期(6周)分别处死1/2幼鼠,取血与左股骨标本。测血骨钙素水平,以股骨钙与股骨长计算股骨含钙指数。实验建立低钙与低VitD动物模型。结果发现严重低钙幼鼠股骨生长显著落后,VitD缺乏幼鼠股骨生长与正常组相似。低钙与VitD缺乏幼鼠股骨含钙指数均明显低于正常组,低钙组更严重。低钙组幼鼠血骨钙素水平略高于正常组,VitD缺乏幼鼠血骨钙素有增高趋势;提示低钙时股骨增生的成骨细胞活性低下,VitD缺乏幼鼠骨生长受阻程度不如低钙组明显,推测VitD缺乏与低钙时对成骨细胞的作用机理不同。本文研究证实低钙对生长期骨骼的影响远远超过临床估计。     

Ursodeoxycholic Acid Enhances Fractional Calcium Absorption in Primary Biliary Cirrhosis

Bone disease is a frequently reported complication in primary biliary cirrhosis (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is the treatment of choice in PBC, improving survival, but its effect on calcium absorption is unknown. In this study, we have measured fractional calcium absorption, using a single isotope method, in a group of female PBC patients (median age: 60 years, range: 46–78 years) and age-matched female controls (median age: 58 years, range: 36–74). Bone mineral density (BMD) in PBC patients was significantly lower than age-matched controls (g/cm²± SEM; lumbar spine: controls 1.139 ± 0.028, PBC patients 1.004 ± 0.026, p= 0.0028; femoral neck: controls 0.944 ± 0.034, PBC patients 0.819 ± 0.023, p = 0.0032). Twenty two PBC patients, who were not vitamin D-deficient, were off and on UDCA for ~1 month and ~8 weeks, respectively. Fractional calcium absorption in PBC patients prior to UDCA treatment (mean ± SEM, 33.8 ± 2.6%) was significantly lower than controls (52.0 ± 2.4%, p<0.001). Following UDCA therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1 ± 2.6%, On UDCA: 36.6 ± 2.5%, p<0.0058). Osteocalcin levels were significantly raised in the PBC group (mean ± SEM, ng/ml, 41.4 ± 2.02) compared to controls (31.1 ± 2.64, p= 0.002). There were no differences in parathyroid hormone (PTH) or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy. In conclusion, we found that PBC patients display low spinal and femoral neck BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The calcium malabsorption is corrected partially by UDCA therapy. Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC. Received: 27 November 2001 / Accepted: 11 April 2002     

Bone gla: Protein in blood derived directly from human bone tissue

Summary In order to find out whether the concentration of bone gla-protein (BGP) is elevated in blood derived directly from bone tissue compared to peripherically sampled blood a peroperative model was used. Blood was collected simultaneously from an armvein and from the osteotomized surface of the bone during total hip replacement in 18 patients Peripheral blood was also collected before the anaesthetic procedure. The anaesthetic and/or the operative procedure slightly decreased the level of BGP in the peripheral blood during this short time interval, but serum BGP was not different in the bone-marrow derived blood and in the peripheral blood taken simultaneously. These data suggest that BGP released from bone into the circulation is rapidly cleared from the marrow and that peripheral serum BGP is a valid index of the bone-derived levels of BGP.