Copy number variation in CNP267 region may be associated with hip bone size

Osteoporotic hip fracture (HF) is a serious global public health problem associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of key measurable risk factors for HF, independent of bone mineral density (BMD). Hip BS is highly genetically determined, but genetic factors underlying BS variation are still poorly defined. Here, we performed an initial genome-wide copy number variation (CNV) association analysis for hip BS in 1,627 Chinese Han subjects using Affymetrix GeneChip Human Mapping SNP 6.0 Array and a follow-up replicate study in 2,286 unrelated US Caucasians sample. We found that a copy number polymorphism (CNP267) located at chromosome 2q12.2 was significantly associated with hip BS in both initial Chinese and replicate Caucasian samples with p values of 4.73E-03 and 5.66E-03, respectively. An important candidate gene, four and a half LIM domains 2 (FHL2), was detected at the downstream of CNP267, which plays important roles in bone metabolism by binding to several bone formation regulator, such as insulin-like growth factor-binding protein 5 (IGFBP-5) and androgen receptor (AR). Our findings suggest that CNP267 region may be associated with hip BS which might influence the FHL2 gene downstream.     

Associations between physical activity and bone mass in black and white South African children at age 9 yr.

We investigated differences in physical activity (PA) levels between black and white South African 9-yr-old children and their association with bone mineral content (BMC) and density (BMD) by using dual-energy X-ray absorptiometry. PA was analyzed in terms of a metabolic (METPA; weighted metabolic score of intensity, frequency, and duration) and a mechanical (MECHPA; sum of all ground reaction forces multiplied by duration) component. There were significant ethnic differences in patterns of activity. White children expended a significantly greater energy score (METPA of 21.7 +/- 2.9) than black children (METPA of 9.5 +/- 0.5) (P < 0.001). When children were divided into quartiles according to the amount and intensity of sport played, the most active white children (using METPA scores) had significantly higher whole body BMD and higher hip and spine BMC and BMD than less active children. White children in the highest MECHPA quartile also showed significantly higher whole body, hip, and spine BMC and BMD than those children in the lowest quartile. No association between exercise and bone mass of black children was found. In this population, PA has an osteogenic association with white children, but not black children, which may be explained by the lower levels of PA in the black children. Despite this, black children had significantly greater bone mass at the hip and spine (girls only) (P < 0.001) even after adjustment for body size. The role of exercise in increasing bone mass may become increasingly critical as a protective mechanism against osteoporosis in both ethnic groups, especially because the genetic benefit exhibited by black children to higher bone mass may be weakened with time, as environmental influences become stronger.     

PHACTR3基因与中国汉族和美国高加索人群骨密度的关联研究

研究组前期的全基因组关联研究发现PHACTR3基因与骨折关联,为了检测该基因与骨密度的关联关系,采用精细定位关联研究来检测PHACTR3基因内及其附近的SNPs与骨密度的关系。首先在中国样本（1627个不相关的汉族样本）和美国样本（2286个不相关高加索样本）中对PHACTR3基因的140个SNPs进行基因分型,然后采用Plink软件检测PHACTR3基因与腰椎和髋部骨密度的关联关系。发现研究组以前报道的与骨折关联的SNPs rs1555364和rs6064822与腰椎和髋部骨密度关联（P=4．89×10^-2-1．26×10^-2）。另外还发现位于PHACTR3基因内含子中3个SNPs位点（rs6027138,rs1182531和rs1182532）与中国人群和白人腰椎骨密度均显著关联,将中国人与白人样本合并起来进行荟萃分析（Meta—analysis）,得到合并P值为1．40×10^-3到4．00×10^-4,另外发现rs6064820与髋部BMD相关联,合并P值为6．70×10^-3。本研究进一步证实了PHACTR3基因在骨密度变异中的作用,对骨质疏松发病机制的认识提供了新的理论依据。     

Effects of raloxifene on changes in bone density

Raloxifene hydrochloride therapy effectiveness in bone mineral density (BMD) changes compared to calcium and vitamin D3 therapy over a 2-year period. Case-control study: a group of 254 women was prescribed raloxifene (raloxifene hydrochloride) together with calcium and vitamin D3 while other group of 254 women used calcium and vitamin D3 therapy. BMD was measured at the hip, spine and forearm at the beginning and at the end of the 2-year period. Treatment with raloxifene resulted in a 3.7% increase in BMD at the spine in 98% of examinees. A 1.2% BMD increase was shown in 75% of examinees at the hip. A 1.2% decrease in BMD at forearm shown in 93% of examinees using raloxifene. The calcium and vitamin D3 therapy led to an increase in BMD in 58% examinees at the spine, in 56% at the hip and in 38% at the forearm, which was significantly lower than in women using raloxifene. Among women using calcium and vitamin D alone an average BMD decrease of 1.2% was registered on 42% of examinees at the spine, 2.6% decrease on 46% of examinees at the hip and 4.2% decrease on 35% of examinees at the forearm. Treatment with raloxifene resulted in a significant increase in BMD at the spine with odds ratio (OR 5.85, p <0.05) compared with calcium and vitamin D3 alone. There was no statistically proven increase in BMD at either the hip (OR 0.015) or forearm (OR 0.122).     

Vitamin D receptor gene polymorphisms,bone mineral density and bone turnover: FokI genotype is related to postmenopausal bone mass

The relationship between vitamin D receptor (VDR) intragenic polymorphisms FokI, BsmI, ApaI and TaqI and bone mineral density (BMD) or biochemical markers of bone remodeling were investigated in 114 Czech postmenopausal women, on the average 62.5+/-8.9 years of age. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in the VDR locus. Bone mineral density was measured at the lumbar spine and at the hip by dual-energy X-ray absorptiometry (DEXA, g/cm2). After adjusting for age and the body mass index (BMI), subjects with the ff genotype had 9.4% lower BMD at the hip than those with the Ff genotype (p=0.0459, Tukey's test). FF individuals had an intermediate BMD at the hip. A similar pattern of lower lumbar spine BMD was also found in ff individuals, but it did not reach statistical significance. There was no relationship between BsmI, ApaI and TaqI VDR polymorphisms and BMD at any skeletal site. Subjects with Aa (ApaI) genotypes had higher levels of propeptide of type I collagen (PICP) than homozygous AA (p=0.0459, Tukey's test). In FokI, BsmI and TaqI restriction sites the biochemical markers of bone remodeling did not differ by genotype. In addition, no significant difference was observed in VDR genotypic distribution between osteoporotic women and non-osteoporotic controls in the study group. To conclude, the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident.     

Pregnancy-associated changes in bone density and bone turnover in the physiological state: prospective data on sixteen women.

Areal bone mineral density (BMD, g/cm 2) was measured for the total body, lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) before pregnancy and after delivery in sixteen women aged 21 - 35 years. Additional measurements included quantitative ultrasound indices (broadband ultrasound attenuation, BUA, at the calcaneus at baseline and at 16, 26, and 36 weeks of pregnancy, and postpartum) as well as biochemical markers of bone formation and resorption (measured before pregnancy and during pregnancy at 16, 22, 26, 30, 34, and 36 weeks of pregnancy and postpartum). The results of measurements were as follows: 1. Postpartum BMD showed a significant reduction in the total body (- 13.4 %), in the spine (- 9.2 %) and in the hip (-7.8 % at the femoral neck and - 9.2 % at the Ward's triangle) compared to pre-pregnancy values. 2. Biochemical markers of bone resorption increased by 26 weeks. 3. Bone ultrasound measurements that provide information on bone density before delivery did not change throughout pregnancy. A significant reduction of BUA (- 14.5 % compared to baseline) was observed postpartum only. These data would suggest that pregnancy-induced bone loss develops rapidly after the 36 week of pregnancy, possibly via enhanced bone resorption.     

The pathophysiological implications of circulating androgens on bone mineral density in a normal female population

In this cross-sectional study performed on 147 healthy or osteoporotic, but otherwise normal premenopausal (n = 26 and n = 13, respectively) or postmenopausal (n = 40 and n = 68, respectively) women aged 40.1+/-9.9 and 61.9+/-8.9 years, respectively (range 20-82 years), serum ovarian and adrenal sex steroids and their relationship to bone mineral density (BMD) were evaluated. The levels of dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (AD), and estradiol correlated positively with BMD at the hip and spine as did serum testosterone with BMD at the spine. An inverse relationship was found between sex hormone binding globulin (SHBG) levels and BMD at the spine and hip. After adjustment for age, body mass, and sex steroid confounders, the bioavailable testosterone value (but not the DHEAS, DHEA, AD, or SHBG) values was demonstrated to be an independent determinant of BMD at the spine (beta 0.18, P<0.02) and hip (beta 0.24, P<0.02). Similarly, estradiol was found to be an independent determinant of BMD at the spine (beta 0.25, P<0.007). However, only SHBG levels (but not other steroid parameters) correlated positively with indices of bone remodeling, namely, serum osteocalcin and cross-linked telopeptide of type I collagen (ICTP). The present study suggests that a major decline in index of free testosterone (testosterone/SHBG) may influence the development of female osteoporosis. The clinical significance of circulating SHBG levels in the assessement of bone metabolic turnover remains to be established.     

Glucocorticoid-induced osteoporosis: a cross-sectional study.

We studied 70 patients (48 women and 22 men) with either rheumatic disease (n = 25) or lung disease (n = 45) who had been treated with glucocorticoids for at least 6 months (mean cumulative dose, 24.2 +/- 27.1 g of prednisone; mean current dose, 11.0 +/- 8.6 mg/d, mean duration of therapy, 8.1 years. We measured bone mineral density (BMD) of the hip (femoral neck) and spine (L2-L4) using dual-photon absorptiometry and BMD of the distal one third radius using single-photon absorptiometry. Compared with age-matched controls, the study population had decreased BMD of the spine (87.0%), hip (87.2%), and radius (90.6%). Current dose, cumulative dose, and duration of therapy were not correlated with BMD in the spine or hip in the total study population. The most significant correlations with low bone mass at the hip and spine were short height and low weight. There was a high incidence of hypercalciuria (30%) as compared with an age- and sex-matched control group (6.4%). Glucocorticoids are known to decrease vertebral and radial bone density. We conclude that glucocorticoids also decrease hip bone density as measured at the femoral neck. The high incidence of hypercalciuria may have implications for therapy of glucocorticoid-induced osteoporosis.     

Parathyroid hormone gene with bone phenotypes in Chinese

Osteoporosis is a common disorder afflicting old people. The parathyroid hormone (PTH) gene is involved in bone remodeling and calcium homeostasis, and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of PTH gene with bone mineral density (BMD) and bone mineral content (BMC), two important risk factors for osteoporosis. A sample of 1263 subjects from 402 Chinese nuclear families was used. The families are composed of both parents and at least one healthy daughter aged from 20 to 45 years. All the subjects were genotyped at the polymorphic BstBI site inside the intron 2 of the PTH gene (a nucleotide substitution of G to A at the position +3244). BMD and BMC were measured at the lumbar spine and the hip region via dual-energy X-ray absorptiometry (DXA). Using QTDT (quantitative trait transmission disequilibrium test), we did not find significant results for association or linkage between the PTH gene and BMD or BMC variation at the spine or hip. Our data do not support the PTH gene as a quantitative trait locus (QTL) underlying the bone phenotypic variation in the Chinese population.     

Association between estrogen receptor alpha gene polymorphisms and bone mineral density in Polish female patients with Graves' disease

Graves' (GD) hyperthyroidism leads to reduced bone mineral density (BMD) accompanied by accelerated bone turnover. Ample studies have identified association between estrogen receptor (ESR1) gene polymorphism and decreased BMD and osteoporosis. In contrast, number of publications that link ESR1, BMD and Graves' disease is limited. The purpose of this study was to identify the association between ESR1 polymorphisms and BMD in premenopausal women with GD and to determine whether ESR1 polymorphic variants can predispose to GD. The study included 75 women aged 23-46 years with GD and 163 healthy controls. BMD was measured at lumbar spine and femoral neck. We investigated two SNPs in the ESR1 gene and analyzed genetic variants in the form of haplotypes reconstructed by statistical method. Three out of four possible haplotypes of the PvuII and XbaI restriction fragment length polymorphisms were found in GD patients: px (55.3 %), PX (33.3 %) and Px (11.4 %). Women homozygous for xx of XbaI and for pp of PvuII had the lowest BMD at lumbar spine. Moreover, the px haplotype predisposed to reduced lumbar BMD. No associations were observed for femoral neck BMD. No statistically significant relationship were found between ESR1 polymorphisms or their haplotypes and GD. These results indicate that the PvuII and the XbaI polymorphisms of ESR1 gene are associated with bone mineral density in premenopausal women with GD and may help to estimate the risk of bone loss particularly at lumbar spine. However, none of the ESR1 gene alleles predict the risk of GD in Polish female patients.     

Vitamin d status and its relationship with bone mineral density and parathyroid hormone in southeast asian adults with low bone density

ObjectiveTo investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.MethodsIn total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.ResultsThe mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine(P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip(P = .035) and the lumbar spine (P = .019). At levels < 30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).ConclusionAmong this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations < 30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health. (Endocr Pract. 2011;17:226-234)     

Growth hormone and bone health

Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle.     

Low bone mineral density in men with chronic obstructive pulmonary disease

Background

Osteoporosis is common in patients with COPD but the likely multi-factorial causes contributing to this condition (e.g. sex, age, smoking, therapy) mask the potential contribution from elements related to COPD. In order to study osteoporosis and bone mineral density (BMD) related to COPD, we studied a well-defined group of patients and controls.

Methods

BMD, forced expiratory volume in one second (FEV₁), circulating bone biomarkers and biochemistry were determined in 30 clinically stable male ex-smokers with confirmed COPD and 15 age matched "ex-smoker" male controls. None of the patients were on inhaled corticosteroids or received more than one short course of steroids.

Results

Mean (SD) FEV₁% predicted of patients was 64(6)%, the majority having Global Initiative for Chronic Obstructive Lung Disease (GOLD) II airflow obstruction. There were 5/30 patients and 1/15 controls who were osteoporotic, while a further 17 patients and 5 controls were osteopenic. The BMD at the hip was lower in patients than controls, but not at the lumbar spine. Mean values of procollagen type 1 amino-terminal propeptide and osteocalcin, both markers of bone formation, and Type 1 collagen β C-telopeptide, a marker of bone resorption, were similar between patients and controls. However, all bone biomarkers were inversely related to hip BMD in patients (r = -0.51, r = -0.67, r = -0.57, p < 0.05) but did not relate to lumbar spine BMD. 25-OH Vitamin D was lower in patients.

Conclusions

Men with COPD had a greater prevalence of osteoporosis and osteopenia than age matched male controls, with a marked difference in BMD at the hip. Bone biomarkers suggest increased bone turnover.     

Estrogen receptor alpha and vitamin D receptor gene polymorphisms and bone mineral density: association study of healthy pre- and postmenopausal Chinese women

In the present study, we tested the association between the estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes with bone mineral density (BMD). A total of 649 healthy Chinese women, classified as pre-menopausal (N=388) and post-menopausal (N=261) groups, were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI sites. BMDs at the lumbar spine (L(1)-L(4)) and total hip were measured by dual-energy X-ray absorptiometry. For the VDR ApaI locus, AA carriers had lower spine BMD than Aa (p=0.02) and aa carriers (p<0.01) in the pre-menopausal group. For the ER-alpha gene, carriers of haplotype px had lower spine BMD than the non-carriers (p=0.03) in the pre-menopausal group. Furthermore, we observed significant interaction between the ER-alpha and VDR genes in the post-menopausal group: with AA genotype (or A allele) at the VDR ApaI locus, pX carriers had higher spine BMD than the non-carriers (p=0.02), and PX carriers had lower hip BMD than the non-carriers (p=0.04). Our data suggest that the ER-alpha and VDR genes may be associated with the BMD variation in Chinese women.     

ZBTB40基因与中国汉族人群和美国高加索人群骨密度的关联研究

最近的全基因组关联研究发现ZBTB40(zinc finger and BTB domain containing 40)基因是一个潜在的调节骨密度的新基因,为了可靠地验证该基因与骨密度的关联关系,采用精细定位关联研究来检测ZBTB40基因内及其附近的SNPs与骨密度的关系.首先在中国样本(1 627个不相关的汉族样本)和美国样本(2 286个不相关高加索样本)中对ZBTB40基因的50个SNPs进行基因分型,然后采用Plink软件检测ZBTB40基因与腰椎和髋部骨密度的关联关系.证实了以前报道的SNPs rs7524102与腰椎和髋部骨密度的关联关系.另外还发现5个SNPs(rs10917209、rs6426748、rs4433361、rs3856183和rs7550872)与腰椎和髋部骨密度相关联.其中最显著的SNP是位于ZBTB40基因上游区域的rs6426748,其与腰椎骨密度的关联P值为9.82×10-4,多重检验校正后仍然显著.连锁不平衡分析表明rs6426748与rs10917209,rs7524102和rs7550872呈现高度连锁关系,位于长度为27 kb的单体型块内,因此ZBTB40基因的功能致病位点可能是rs6426748或该单体型块内某一未分型的SNP.     

Power training is more effective than strength training for maintaining bone mineral density in postmenopausal women.

Physical exercise has a favorable impact on bones, but optimum training strategies are still under discussion. In this study, we compared the effect of slow and fast resistance exercises on various osteodensitometric parameters. Fifty-three postmenopausal women were randomly assigned to a strength training (ST) or a power training group (PT). Both groups carried out a progressive resistance training, a gymnastics session, and a home training over a period of 12 mo. During the resistance training, the ST group used slow and the PT group fast movements; otherwise there were no training differences. All subjects were supplemented with Ca and vitamin D. At baseline and after 12 mo, bone mineral density (BMD) was measured at the lumbar spine, proximal femur, and distal forearm by dual-energy X-ray absorptiometry. We also measured anthropometric data and maximum static strength. Frequency and grade of pain were assessed by questionnaire. After 12 mo, significant between-group differences were observed for BMD at the lumbar spine (P < 0.05) and the total hip (P < 0.05). Whereas the PT group maintained BMD at the spine (+0.7 +/- 2.1%, not significant) and the total hip (0.0 +/- 1.7%, not significant), the ST group lost significantly at both sites (spine: -0.9 +/- 1.9%; P < 0.05; total hip: -1.2 +/- 1.5%; P < 0.01). No significant between-group differences were observed for anthropometric data, maximum strength, BMD of the forearm, or frequency and grade of pain. These findings suggest that power training is more effective than strength training in reducing bone loss in postmenopausal women.     

The association between major depressive disorder,use of antidepressants and bone mineral density (BMD) in men

Objective:

Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men.

Methods:

Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression.

Results:

Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site).

Conclusions:

Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men.     

α2-HS 糖蛋白基因与中国人群的髋部骨大小的相关性研究

骨大小是一种独立于骨密度（BMD）的骨质疏松性骨折的重要风险因子。由于其高遗传率,充分了解控制骨大小的遗传因素有很重要的临床意义。文章研究目的为检测中国人群中α2-HS糖蛋白基因（AHSG）多态性和腰椎及髋部骨大小变异之间的关联。我们总共征集了来自中国401个核心家庭（包括父母亲及至少一个女儿）的1260个研究样本,并且分型了AHSG基因第7个外显子的Sac Ⅰ位点多态性。该位点核苷酸的替换（C→G）引起第238号丝氨酸被苏氨酸取代,因此可能对基因功能有影响。在任何骨骼位点,没有发现显著的群体分层。发现-HSG基因SacⅠ位点多态性和转子间（P=0．019）以及全髋的（P=0．035）骨大小呈显著性相关。该多态性位点能分别解释转子间和全髋3．74％和3．16％的骨大小变异。连锁分析没有检测到显著性结果,可能的主要原因是样本中同胞对的数目较少,统计效力较低,以及SacⅠ位点多态相对于微卫星标记对连锁分析提供的信息量少。结果表明,月HSG基因多态性可能和中国人群中髋部骨大小变异有关。     

Milk consumption and bone mineral density in middle aged and elderly women.

OBJECTIVES--To study the effects of historical milk consumption on current bone mineral density at the hip and spine. DESIGN--Cross sectional study. SUBJECTS--284 community based women aged 44-74 years recruited from four general practice age-sex registers in Cambridge. Subjects categorised their average milk consumption up to age 25, from age 25-44, and from age 44 to the present time as > or = 1 glass/day, < 1 glass/day but > 1 glass/week, or < 1 glass/week. MAIN OUTCOME MEASURES--Bone mineral density at the hip and spine measured by dual energy x ray absorptiometry. RESULTS--Data on milk consumption up to age 25 years were available for 252 women. There was a consistent upward trend in bone mineral density at all sites with increasing historical milk consumption (total hip, femoral neck, trochanter, intertrochanter, P < 0.05; Ward''s triangle, P = 0.005). Adjustment for age and body size did not alter these trends. Milk consumption up to age 25 was a significant independent predictor of bone mineral density at all sites in multiple linear regression analyses controlling for age, body mass index, menopausal status, smoking, ever use of hormone replacement therapy or oral contraceptives, physical activity, and alcohol intake. The effects of milk consumption from age 25-44 and from age 44 to the present were similar in direction though not statistically significant. CONCLUSION--Frequent milk consumption before age 25 favourably influences hip bone mass in middle aged and older women.     

不同程度老年骨质疏松患者血清BALP、OPG/PYR比值变化及其与骨密度、骨折发生的相关性分析

摘要 目的：分析不同程度老年骨质疏松患者血清骨特异性碱性磷酸酶(BALP)、骨保护素(OPG)/吡啶啉(PYR)比值变化及其与骨密度、骨折发生的相关性。方法：选择我院自2020年11月至2023年7月接诊的70例老年骨质疏松患者作为观察组,其中轻-中度骨质疏松44例、重度骨质疏松26例;另选70例老年非骨质疏松者作为对照组。检测所有受试者血清BALP、OPG/PYR比值、腰椎、股骨颈和髋部的骨密度(BMD),分析BALP、OPG/PYR比值与不同骨骼部位BMD的关系,使用受试者工作特征(ROC)曲线分析BALP、OPG/PYR比值对老年骨质疏松骨折的预测效能。结果：观察组血清BALP水平高于对照组,OPG/PYR比值小于对照组（P＜0.05）;重度骨质疏松组血清BALP水平高于轻-中度骨质疏松组,OPG/PYR比值小于轻-中度骨质疏松组（P＜0.05）;观察组腰椎、股骨颈及髋部的BMD均小于对照组（P＜0.05）;经Pearson相关性分析,腰椎、股骨颈及髋部的BMD与血清BALP水平呈负相关（P＜0.05）,与OPG/PYR比值呈正相关（P＜0.05）;经ROC曲线分析,血清BALP联合OPG/PYR比值预测老年骨质疏松骨折的AUC为0.890。结论：老年骨质疏松患者血清BALP水平升高、OPG/PYR比值减小,与病情严重程度及骨密度有关,联合预测骨折的效能较好,值得进一步研究应用。