Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women

OBJECTIVE: To investigate the relationship of osteocalcin and matrix Gla protein (MGP) gene polymorphisms to serum osteocalcin levels, and bone mineral density (BMD) in postmenopausal Korean women. DESIGN: The osteocalcin gene Hind III and MGP gene cytosine-adenine polymorphisms were analyzed in 267 postmenopausal Korean women. Serum osteocalcin, bone alkaline phosphatase, C-telopeptide of type I collagen, and BMD at the lumbar spine and femoral neck were measured. RESULTS: No significant differences in BMD of the lumbar spine and femoral neck were observed across MGP genotypes, whereas a significant lower BMD at the lumbar spine (but not at the femoral neck) was observed in women with the (h) allele (lower case 'h' signifies the presence of the Hind III site) in a dose-response manner. Serum osteocalcin levels among bone turnover markers studied were significantly higher in women without the 210-bp MGP (cytosine-adenine) allele, or with the osteocalcin hh genotype. CONCLUSIONS: The osteocalcin gene Hind III polymorphism is a genetic factor that is associated with BMD of the lumbar spine in Korean women, and Gla gene polymorphisms are associated with higher osteocalcin levels.     

Urinary NTX results rarely alter the clinical management of patients with osteoporosis in the tertiary hospital

AIM: Urinary levels of cross-linked N-terminal telopeptide of type I collagen (NTX) are used as a marker of bone resorption and are useful for monitoring response of patients treated with anti-resorptive agents. We aimed to determine how urinary NTX results alter clinical decision making by physicians treating patients with osteoporosis in a tertiary hospital setting. METHODS: We reviewed patient notes of all new NTX requests in 2002 and 2003 with at least one subsequent repeat measurement. Patients with a diagnosis of osteoporosis and both pre- and post-treatment measurements of bone mineral density (BMD) and NTX were included. Urinary NTX was measured with the Osteomark enzyme-linked immunosorbent assay. BMD of the hip and lumbar spine was measured using dual energy X-ray absorptiometry (DEXA). RESULTS: A total of 357 patients had serial NTX requests during the time period. Sixty-five of these patients had a diagnosis of osteoporosis. Out of 37 patients treated for osteoporosis who had complete data available, 29 patients had concordant results between BMD and NTX and eight patients had discordant results. Only one patient had treatment changed as a result of a lack of reduction in NTX following treatment. Thirteen patients had therapy altered. Common reasons for altering therapy were patient non-compliance, side effects and failure of BMD to increase. CONCLUSIONS: Alteration to therapy in this patient population is mainly dictated by issues such as patient compliance, medication side effects and bone mineral density results rather than urinary NTX values.     

Bone tissue metabolism in men with ankylosing spondylitis

PurposeThe aim of the study was the composite estimation of bone tissue metabolism in ankylosing spondylitis (AS) after having taken into account such factors as a high risk of incidence of osteoporosis in patients with AS and potential danger of permanent immobility.Material and MethodsSixty- six patients with established diagnosis of AS and 63 healthy individuals in the control group were included into the study. To measure bone mineral density (BMD) the dual energy X-ray absorptiometry (DEXA) method was used. Additionally, biochemical markers of osteoporosis such as bone fraction of an alkaline phosphatase (BALP), osteocalcin (BGP) and deoxypyridinoline (Dpd) as well as many inflammatory markers of disease activity have been determined.ResultsIn our study with AS had significantly diminished bone mineral density, as compared with health controls. The presence of osteopenia/osteoporosis was associated with longer duration of the disease and with higher age. In the overall group of AS patients bone degradation marker, Dpd, correlated with serum concentration of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP), and inversely with BMD measured in the forearm. However, no direct association could be revealed between lower bone density and markers of inflammation or inflammatory cytokines, except of IL-6 witch was significantly higher in AS patients with osteoporosis/ osteopenia than those without.ConclusionsOur results indicate that disease duration and higher age are risk factors for osteoporosis in patients with AS. Inflammation might contribute to the accelerated bone loss in AS through stimulation of bone degradation.     

The antioxidant enzyme GPX1 gene polymorphisms are associated with low BMD and increased bone turnover markers

Recently, oxidative stress has been suggested as participating in the development of osteoporosis. Glutathione peroxidase 1 (GPX1) is one of antioxidant enzymes responsible for the defence of cells against oxidative damage and thus for protection against age related diseases such as osteoporosis. The aim of present study was to associate genetic variances of GPX1 enzyme with bone mineral density (BMD) and biochemical bone turnover markers and to show the influence of antioxidative defence system in genetics of osteoporosis. We evaluated 682 Slovenian subjects: 571 elderly women and 111 elderly men. All subjects were genotyped for the presence of GPX1 gene polymorphisms Pro198Leu and polyAla region. BMD and biochemical markers were also measured. General linear model analysis, adjusted to height, and (one-way) analysis of variance were used to assess differences between the genotype.and haplotype subgroups, respectively. The significant or borderline significant associations were found between the polyAla or the Pro198Leu polymorphisms and total hip BMD (0.018; 0.023, respectively), femoral neck BMD (0.117; 0.026, respectively) and lumbar spine BMD (0.032; 0.086, respectively), and with biochemical bone turnover markers such as plasma osteocalcin (0.027; 0.025, respectively) and serum C-terminal telopeptide of type I collagen concentrations (0.114; 0.012, respectively) in whole group. Haplotype analysis revealed that the 6-T haplotype is associated significantly with low BMD values (p< 0.025) at all measured locations of the skeleton, and with high plasma osteocalcin concentrations (p=0.008). This study shows for the first time that the polymorphisms polyAla and Pro198Leu of the GPX1 gene, individually and in combination, are associated with BMD and therefore may be useful as genetic markers for bone disease. Moreover, it implies the important contribution of the oxidative stress to pathogenesis of osteoporosis.     

Bone mineral density,bone turnover markers,lean mass,and fat mass in Egyptian children with congenital adrenal hyperplasia

Introduction

Aim of this paper is to assess bone mineral density (BMD) and body composition, by dual energy X-ray absorptiometry (DXA), and various markers of bone growth, in a group of children with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid therapy.

Material and methods

A case-control study included thirty patients with CAH with different states of metabolic control. Their mean age was 7.5 ±4.2 years. All patients are subjected to BMD using DXA at the neck of the femur and lumbar spine. A blood sample was taken for assessment of osteocalcin, osteoprotegerin, and procollagen type 1, as markers of bone formation, as well as RANKL and urinary deoxypyridinoline (DPD), as markers of bone resorption.

Results

We found no difference in BMD in patients and control subjects; however, patients showed significantly lower serum osteocalcin (p = 0.008) and osteoprotegerin (p = 0.0001) and significantly higher serum RANKL levels (p = 0.0001). Our results show that patients had significantly lower lean body mass (p = 0.005) and fat/lean ratio (p = 0.008) compared to matched controls. The duration of treatment showed a significant negative correlation with procollagen type 1 (r = –0.49, p = 0.02) and lean mass % (r = –0.43, p = 0.04); however, it showed a significant positive correlation with total fat mass % (r = 0.6, p = 0.0006), and fat/lean ratio (r = 0.43, p = 0.04). Dose of steroid had a significant positive correlation with BMI SDS (r = 0.4, p = 0.02).

Conclusions

Bone mineral density is normal but bone turnover is low in patients with CAH. There is an increase in fat/lean mass in patients with CAH.     

Evaluation of bone metabolism and bone mass in patients with type-2 diabetes mellitus

The objectives of this study were to determine whether type-2 diabetes was associated with a higher bone mineral density (BMD) in men and women and to evaluate the differences in mineral metabolism between diabetic and normal subjects by using biochemical bone turnover markers. In this study, 52 patients (37 females/15 males) aged 41-64 with type-2 diabetes mellitus and 48 nondiabetic control subjects (34 females/14 males) were evaluated. In men, BMD was significantly higher in diabetics at the forearm (p <0.05), whereas in women tended to be higher at the hip (p=0.002). Serum osteocalcin (p<0.0001), bone alkaline phosphatase (BAP) (p<0.05) and carboxyterminal telopeptide (CTx) (p<0.05) were higher in the control group than in diabetics. In men, serum osteocalcin (p<0.05) and CTx (p<0.005) and, in women, serum osteocalcin (p<0.0001) and BAP (p<0.05) were lower in diabetic subjects. In conclusion, our findings suggest that although bone formation is decreased in type-2 diabetes, diabetic patients are not susceptible to bone resorption. This low bone turnover can slow the rate of bone loss and cause a higher bone density than expected for their age.     

Effect of physical activity on bone turnover in young boys

AIMS: To evaluate the effect of the physical activity on bone turnover in young male soccer players at the Tanner's stage of 1-2. MATERIAL AND METHODS: 61 young soccer players (13,4 +/- 0,3 years old) who actively participated in soccer since 3,7 +/- 0,7 years were compared to 60 age and sex- matched non active subjects. Bone mineral density (BMD) of whole body, and in specific skeleton sites, fatty body mass (FBM) and lean body mass (LBM) were determined by a dual energy X-ray absorptiometry (DXA). Total plasma alkaline phosphatase (ALP) and plasma bone alkaline phosphatase (BALP), plasma osteocalcin (OC) and plasma collagen type I cross-linked C-telopeptide (CTX) were measured. RESULTS: BMD of the whole body and at the lumbar spine (L2-L4), femoral, lower limbs and LBM were significantly higher in young soccer players than in controls. The biochemical markers of bone turnover: ALP (6,7%), BALP (8,9%), OC (3%) and CTX (3,1%) were not significantly higher in sportsmen than in controls. The calcium was significantly higher in sportsmen than in controls. CONCLUSION: These results suggest that soccer practice induced an increase of bone mass in boys. The increase in the level of bone turnover evaluated by the new biochemical markers was not significant in the sportsmen.     

Expression characteristic and significance of interleukin-6, nuclear factor kappa beta, and bone formation markers in rat models of osteoporosis

The goal of this study was to investigate the expression levels of interleukin 6 (IL-6), nuclear factor kappa beta (NF-kappabeta), bone-specific alkaline phosphatase (BALP), and bone osteocalcin (BGP) in rats with osteoporosis and their significance in the pathogenesis of osteoporosis. In all, 60 adult female SD rats were divided randomly into 3 groups of 20 rats each: normal control group (control), sham-operated group (sham), and ovariectomized group (OVX). In 2, 3, 4, 5, and 6 months after surgery, 4 rats were randomized from each group for assays of BMD, IL-6, BALP, and BGP. Then, the rats were sacrificed for the detection of IL-6 and NF-kappabeta expression levels in bone tissue by quantitative real-time RT-PCR analysis. Compared with the sham (0.097 +/- 0.04 g/cm2, 0.097 +/- 0.01 g/cm2, 0.095 +/- 0.07 g/cm2) and control group (0.107 +/- 0.01 g/cm2, 0.103 +/- 0.07 g/cm2, 0.108 +/- 0.06 g/cm2), the BMD of rats in the OVX group was reduced remarkably in 4, 5, and 6 months (0.082 +/- 0.05 g/cm2, 0.073 +/- 0.02 g/cm2, 0.061 +/- 0.05 g/cm2, respectively; P < 0.01); the serum IL-6 level increased significantly from 2 to 6 months after surgery (P < 0.01); and the serum levels of BALP and BGP were greater at 4, 5, and 6 months (P < 0.05). The quantitative real-time RT-PCR analysis demonstrated that IL-6 and NF-kappabeta mRNA levels in OVX group increased in a time-dependent manner. Moreover, the IL-6, NF-kappabeta, BALP, and BGP levels were correlated negatively with the BMD. Meanwhile, a positive correlation was observed between IL-6 and NF-kappabeta. In conclusion, the expression levels of IL-6, NF-kappabeta, and bone formation markers may increase significantly in the osteoporosis rats. These molecules could play a role in the pathogenesis.     

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.     

Predictors of bone disease in Egyptian prepubertal children with β-thalassaemia major

Introduction

Thalassaemic osteopathy is a multifactorial disorder and limited information exists about bone accrual and bone mineral density (BMD) in prepubertal thalassaemic children. The study aimed to investigate some potential genetic and biochemical bone markers as possible early predictors of BMD variations in children with β-thalassaemia major (TM) before puberty.

Material and methods

Thirt-one prepubertal children with β-TM, and 43 matched controls were subjected to BMD assessment by dual energy X-ray absorptiometry (DEXA). Vitamin D receptor (VDR) gene polymorphisms (Bsm1, Fok1) and the biochemical bone markers serum osteocalcin and propeptide I procollagen (CPIP) and urinary deoxypyridinoline (DPD) excretion were assessed.

Results

Bone mineral density was reduced in 25% of thalassaemics at the spine and 15.4% at the hip region. Significantly higher levels of urinary DPD and lower serum osteocalcin and CPIP levels were found in the studied thalassaemic children compared to controls (p < 0.001). A significant negative correlation was present between BMD in spine and hip and the patients’ age (r = −0.6367, p = 0.0002 and r = −0.616, p = 0.00079, respectively). There was a significant reduction in BMD in males compared to females. Reduced BMD was more frequent in male patients with genotypes bb and Ff but not in females. Bone mineral density was not related to the studied biochemical bone markers, mean pre-transfusion haemoglobin or serum ferritin.

Conclusions

Routine BMD screening with DEXA is proposed to be a sensitive predictor for early bone changes, particularly at the lumbar spine. DR gene polymorphisms of Bsm1 and Fok1 polymorphisms may be determinants of BMD in Egyptian prepubertal male thalassemics     

An investigation of ethnic differences in bone mineral, hip axis length, calcium metabolism and bone turnover between West African and Caucasian adults living in the United Kingdom.

The aim of the study was to investigate factors relating to calcium and bone metabolism which might explain the low incidence of osteoporotic fracture among Africans. Adult bone mineral status, hip axis length and biochemical indices were investigated in 20 Caucasians (10 male, 10 female) and 19 Gambians (12 male, 7 female) living in the UK. Bone mineral content (BMC), bone mineral density (BMD) and BMC adjusted for bone area, body weight and height (size-adjusted BMC) were measured for the whole-body, lumbar spine, femoral neck, trochanter, radius shaft and radius wrist using dual-energy X-ray absorptiometry. There were no significant differences in whole body or regional BMC; values tended to be lower in the Gambians. Gambian men had higher size-adjusted BMC at the femoral neck (Gambian-British = 21%, 95% CI = 6 to 36%, p < 0.01), associated with a smaller bone area (Gambian-British = -11%, 95% CI = -20 to -2%, p = 0.02). BMD was affected similarly. No other significant differences in BMD or size-adjusted BMC were observed. Gambians had shorter hip axis length (Gambian British, after accounting for sex, = -5%, 95% CI = -9 to -1%, p = 0.02). There were no significant differences in bone turnover (osteocalcin, bone isoenzyme of alkaline phosphatase, urinary deoxypyridinoline) or calciotropic hormone levels (parathyroid hormone, 1,25-dihydroxyvitamin D, calcitonin). Gambian men had lower 25-hydroxyvitamin D concentrations (Gambian = 26.3 SD 12.0 nmol/L, British = 55.5 SD 13.9 nmol/L, p < 0.0001), a difference not seen among the women. Gambian men and women excreted significantly less phosphate and potassium than British subjects by 30-60%; urinary calcium and sodium excretion were similar in the two groups. This study revealed few ethnic differences that could account for the disparity in osteoporotic fracture rates between Africans and Caucasians, with the possible exception of anatomical differences in the hip.     

绝经前期妇女血清PINP、ICTP和25-OH-VitD_3水平的变化及其与BMD的相关性分析

目的：观察绝经前期妇女血清PINP、ICTP和25-OH-VitD3水平的变化,分析其与骨密度（BMD）的相关性。方法：采用双能X线吸收法（DEXA）对67例绝经前期健康女性进行第（1～4）腰椎（L1-4）、左、右髋部（股骨近段＋股骨颈）的BMD测定,并根据BMD测定结果分为BMD正常组和BMD降低组。用放射免疫分析（RIA）测定血清Ⅰ型前胶原氨基端前肽（PINP）、Ⅰ型胶原交联羧基末端肽（ICTP）和25-羟维生素D3（25-OH-VitD3）,分析与各部位BMD的相关性。结果：①19例出现BMD降低（28.4%）,两组间腰椎及左、右髋部BMD差异显著（P〈0.01）;②BMD减低组的PINP和ICTP[分别为（56.9±18.2）μg/L和（3.78±0.83）μg/L]高于BMD正常组[分别为（43.8±15.1）μg/L和（3.45±0.98）μg/L],其中PINP差异显著（P〈0.05）,25-OH-VitD3水平两组间无显著性差异[分别为（25.6±7.8）ng/ml和（27.4±9.2）ng/ml,P〉0.05];③PINP与L1-4、左股骨近段、左股骨颈的BMD呈正相关（r=0.274～0.402,P〈0.05）,ICTP及25-OH-VitD3与BMD无明显相关性（r=-0.226～0.083,P〉0.05）,PINP与25-OH-VitD3呈一定程度的正相关（r=0.395,P〈0.05）。结论：绝经前期妇女有骨转换增高趋势,BMD检查联合骨转换标志物测定有利于识别绝经前期高风险发生骨质疏松的妇女,以指导OP预防性治疗。     

Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism

BACKGROUND: Although overt hyperthyroidism is a well known cause of bone loss, systemic effects of subclinical hyperthyroidism (SH) are still a matter of debate. Objective: The aim of this cross-sectional study was to evaluate the effect of endogenous SH on bone in relation to the menopausal status. METHODS: Bone mass and turnover were assessed in a group of 60 patients with endogenous SH due to multinodular goitre; 30 of them were premenopausal and 30 early postmenopausal (mean age, 40.9 +/- 7.3 and 57.7 +/- 6.75, respectively). Sixty healthy women matched for age-, BMI- and menopausal status served as controls. Three different skeletal sites were evaluated using two different techniques: lumbar spine and femoral neck were assessed by DEXA whereas the proximal phalanges were evaluated by quantitative ultrasonometry (QUS), measuring the amplitude-dependent speed of sound (Ad-SoS). Serum osteocalcin and urinary deoxypyridinoline (DPD) were also determined as markers of bone turnover. RESULTS: A significant decrease was found in femoral BMD (P < 0.05) and phalangeal Ad-SoS (P < 0.001) in pre- and postmenopausal patients compared to controls, being greater in those postmenopausal. Lumbar BMD was decreased only in postmenopausal patients (P < 0.05). Bone turnover markers were higher in patients than in controls and in post- than in the premenopausal ones. A significant negative correlation was found between femoral BMD, Ad-SoS and serum free T3 levels, the latter considered a marker of disease activity. CONCLUSIONS: A significant increase in bone turnover markers and a decrease in bone mass was found in women affected by endogenous SH, being greater in early postmenopausal patients. Cortical rich bone was mainly affected. Both QUS and the conventional DEXA technique were equally able to determine bone density decrease related to mild thyroid hormone excess and sexual hormone decrease.     

Non-association Between Polymorphisms of the Frizzled Receptor Genes and Bone Mineral Density in Postmenopausal Korean Women

We investigated the association between single nucleotide polymorphisms (SNPs) in the frizzled (FZD) genes in the Wnt signal pathway and circulating osteoprotegerin (OPG), soluble receptor activator of NF-κB ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal women. The SNPs in the FZD1, FZD5, FZD6, FZD7, and FZD9 genes were analyzed by direct sequencing in 371 postmenopausal Korean women. Levels of serum OPG, sRANKL, osteocalcin, C-telopeptide of type I collagen, calcium, parathyroid hormone and calcitonin, and BMD at the lumbar spine and femoral neck were measured. The SNPs in the FZD1, FZD5, FZD7, and FZD9 genes, and in exon 2 of the FZD6 gene were not observed. No significant differences in the adjusted BMD of lumbar spine and femoral neck and serum levels of OPG, sRANKL, and bone markers were noted among the single or haplotype genotypes of the L345M and E664A SNPs in the FZD6 gene and the distributions of these single or haplotype genotypes were not different according to the bone mass status. In conclusion, the polymorphisms of the FZD genes are not associated with BMD of the lumbar spine and femoral neck, bone turnover markers, or circulating OPG-sRANKL in Korean women.     

M2 polarization of monocytes in ankylosing spondylitis and relationship with inflammation and structural damage

The aim of this study was to evaluate the polarization of peripheral blood monocytes in the patients with ankylosing spondylitis (AS) and to determine the correlations between monocyte polarization and inflammation and structural damage. A total of 120 AS patients, 50 rheumatoid arthritis (RA) patients and 100 healthy controls were enrolled in the study. M1 (CD68+CD192+) and M2 (CX3CR1+CD163+) monocytes were characterized by flow cytometry. Demographic, clinical, radiographic and laboratory data were collected and analyzed. A large increase in M2 (CX3CR1+CD163+) monocytes was observed in AS, and M2/M1 ratio was 7.18 ± 6.12, 2.54 ± 3.14 and 35.61 ± 20.04 in control, RA and AS, respectively. The M2/M1 ratio correlated with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (r = 0.565; p < 0.001), ESR (r = ?0.321; p < 0.001, CRP (r = ?0.265; p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (r = ?0.201; p = 0.028). Anti‐TNF‐α therapy induced a significant reduction in the percentage of M1 monocyte, ESR, CRP and BASDAI in AS patients. The present results demonstrated that M2 type polarized monocytes are predominant in the peripheral blood in AS and the M2/M1 ratio is correlated with structural damage (mSASSS), inflammatory biomarkers (ESR and CRP) and BASDAI.     

Cathepsin K predicts femoral neck bone mineral density change in nonosteoporotic peri- and early postmenopausal women

OBJECTIVE: Cathepsin K is a cysteine protease that plays an essential role in organic bone matrix degradation. The aim of our study was to seek correlation of serum cathepsin K levels and a change in bone mineral density (BMD) over a 3-year period in a population of healthy nonosteoporotic women. The secondary end points were the correlations of serum cathepsin K with cross-sectional BMD and with other serum bone turnover markers and age. DESIGN: In 43 healthy women aged 42 to 57 years, blood samples for determination of cathepsin K, osteocalcin, bone alkaline phosphatase, C-terminal cross-linking telopeptide of type I collagen, osteoprotegerin, and nuclear factor kappaB ligand were collected at the time of the first BMD measurement. BMD measurements were repeated after 3 years. RESULTS: We found a moderate negative correlation of serum cathepsin K levels with change in femoral neck BMD, but none with change in spinal BMD. There were no significant correlations between cross-sectional BMD of the spine or femoral neck and serum levels of cathepsin K. Serum levels of cathepsin K were not significantly correlated with any bone turnover markers studied or with age. CONCLUSIONS: Serum cathepsin K does not seem to represent a surrogate for bone turnover markers used at present, but it might be useful as a predictor of cortical bone loss.     

绝经后妇女骨质疏松患者血清IGF-1、IGFBP-3与骨密度及骨代谢指标的关系

目的： 探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）与绝经后妇女骨密度及骨代谢指标之间的关系。方法： 通过检测90例绝经后妇女骨质疏松患者及70例绝经后骨量正常的健康对照组血清IGF-1、IGFBP-3、骨钙素（BGP）、I型胶原异构C端肽（β-CTX）、雌激素（E₂）、降钙素（CT）、甲状旁腺激素（PTH）、钙（Ca）、磷（P）等指标，然后同用双能X线骨密度仪检测的两组研究对象的腰椎（L2-L4）侧位、左股骨颈骨密度进行比较。结果： 绝经后骨质疏松组妇女腰椎、股骨颈骨密度显著低于对照组（均P<0.01）；血清IGF-1、IGFBP-3、E₂、CT、BGP水平均低于对照组（均P<0.01）；血清β-CTX、PTH均高于对照组（均P<0.01），血清Ca、P两组之间无差异（均P>0.05）。骨质疏松组和对照组腰椎侧位、左股骨颈BMD均与IGF-1、IGFBP-3、E₂、BGP、CT水平呈正相关，与β-CTX、PTH水平呈负相关，而与血钙、血磷无明显关系。结论： IGF-1、IGFBP-3、E₂、BGP、CT、β-CTX、PTH血清水平与腰椎、左股骨质具有明显的相关性，通过检测上述指标可考虑作为筛查绝经后妇女是否容易患有骨质疏松症的一项有价值的生化参考指标。     

Soy isoflavones for osteoporosis: an evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.     

Lack of benefit with omega-3 fatty acid supplementation in HIV patients: A randomized pilot study

Objective: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on bone metabolism in HIV-infected patients presenting with hypertriglyceridemia.

Methods: Patients were randomized 1:1 to receive 2?g of n-3 PUFA or fenofibrate (FF). The primary endpoint was % change in bone mineral density (BMD) from baseline to month 24 in lumbar spine (LS) and femoral neck (FN). Secondary endpoints were changes in Z-score, calcitriol, calcitonin, parathyroid hormone, osteocalcin, and C-terminal telopeptide of type I collagen (CTX-I) at 12 and 24?months. Differences in continuous variables were evaluated using the t test or Mann-Whitney U-test for independent samples and differences in means of intra- and inter-subject continuous variables using a general linear model. Categorical variables were compared by the chi-squared or Fisher’s exact test.

Results: 30 patients were included in each arm; 23 in the n-3 PUFA arm and 22 in the FF arm completed follow-up. No significant differences between arms were observed after 24?months in either region (FN: ?12.51% ± 7.89 in the n-3 PUFA arm and -8.18% ± 7.72 in the FF arm, p?=?.07; LS: 2.94% ± 6.63 in the n-3 PUFA arm, ?3.07% ± 16.85 in the FF arm, p?=?.07), although the BMD reduction in the FN region after 24?months was noticeable in both arms (n-3 PUFA: ?12.51% ± 7.89%, p?=<?.001; FF: ?8.183% ± 7.72%, p?=<?.001). There was a significant difference in calcitriol changes between arms after 96?weeks. No differences in Z-score or bone turnover markers were observed between the two arms.

Conclusions: Omega-3 fatty acid supplementation resulted in no beneficial changes in BMD or bone turnover markers. n-3 PUFA supplementation achieved similar reductions in triglyceride levels as FF.     

Effect of raloxifene and clodronate on bone density in postmenopausal osteoporotic women

The aim of the present study was to determine the safety and efficacy of combined therapy with raloxifene (RLX) and clodronate (CLD) in postmenopausal women. We enrolled 45 women with postmenopausal osteoporosis. The patients were randomly assigned to two different therapeutic groups: RLX 60 mg/day (n = 23) and RLX 60 mg/day plus CLD 100 mg intramuscularly (i.m.) once every 10 days (n = 22); 1 g of calcium and 800 IU of vitamin D3 were also given daily to both groups. Lumbar and femoral bone mineral density (BMD) were assessed at baseline and after 12 months of therapy using the dual X-ray absorptiometry technique (Norland XR36). We measured the bone turnover markers NTx and CTx, bone alkaline phosphatase (BAP) and osteocalcin at baseline and after 12 months of therapy. Our data demonstrate that 1 year of combined RLX+CLD therapy induced a higher increase in lumbar BMD than treatment with RLX alone as well as a major decrease in bone resorption markers, suggesting an additive effect of CLD on bone mass and inhibition of bone turnover. Furthermore, after 1 year of therapy levels of bone formation markers (osteocalcin and BAP) had increased in both groups, but the increase in osteocalcin and BAP was significantly higher in the RLX+CLD treated group, suggesting that, in addition to its inhibitory effects on resorption, CLD might also have stimulatory effects on mature osteoblast activity.