Variation In Mineral Density Research Articles

No association between polymorphisms of proliferator-activated receptor-gamma gene and peak bone mineral density variation in Chinese nuclear families

Association between SNPs in polymorphism in peroxisome [corrected] proliferator-activated receptor-gamma (PPARG) and peak bone mineral density (BMD) variation of women was measured in 401 Chinese nuclear families using quantitative transmission disequilibrium test (QTDT). The peak BMD variation was not attributable to PPARG in our sample. The purpose of this study is to test whether genetic PPARG might play a role in normal variation in peak BMD. We genotyped 10 tagging SNPs in PPARG using allele-specific polymerase chain reaction and further test whether these SNPs were associated with peak BMD variation at the lumbar spine and femoral neck of women in 401 Chinese nuclear families using QTDT. Furthermore, the association between these SNPs in PPARG and BMD in 710 postmenopausal Chinese women was measured. Using QTDT for within-family association, we failed to find that single SNP and haplotype were significantly associated with peak BMD at the lumbar spine and femoral neck. Meanwhile, we found that only rs1801282 was significantly associated with BMD at the lumbar spine in postmenopausal women (P = 0.013). Our present results suggest, for the first time, that the genetic polymorphism in PPARG is not a major contributor to the observed variability in peak BMD at the lumbar spine and femoral neck in Chinese women.

Bone mineral density variation in men is influenced by sex-specific and non sex-specific quantitative trait loci

Introduction A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18–61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results A genome wide scan identified significant QTL (LOD > 3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.

The − 9247 T/C polymorphism in the SOST upstream regulatory region that potentially affects C/EBPα and FOXA1 binding is associated with osteoporosis

Accumulating evidence shows that genes that cause monogenic diseases also contribute to similar complex disease in the general population. We sought to determine whether the allelic variation in seven monogenic bone disease genes (CLCN7, TCIRGI, SOST, CA2, CSTK, TGFB1 and SLC26A2) contributes to osteoporosis/bone mineral density (BMD) variation in the normal Chinese population. We conducted a gene-wide tag SNP-based association study in 1243 Chinese subjects with low BMD (Z-scores≤−1.28, equivalent to the lowest 10% of the population) and high BMD (Z-score≥+1.0). Twenty-two tag SNPs were selected and genotyped by using the high-throughput Sequenom genotyping platform. Allelic and haplotype association tests were conducted by Haploview and binary logistic regression analyses. The −9247 polymorphism rs1230399 in the upstream regulatory region of the sclerostin gene showed significant genotypic/allelic associations with spine, femoral neck, trochanter and total hip BMD (P=0.03–0.004). The T-allele of rs1230399 increased the risk of osteoporosis (OR=1.52, P=0.005). Computational analysis showed that rs1230399 is located at the core consensus recognition site of two cooperating transcription factors C/EBPα and FOXA1 that modulate estrogen receptor function. T→C polymorphism abolishes the binding of both C/EBPα and FOXA1 to the sclerostin gene. Our data suggest a mechanistic link between rs1230399 and BMD through estrogen ERα/FOXA1 signaling pathways driven by long-distance enhancers.

Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation

Bone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD.

Identification ofLTBP2on Chromosome 14q as a Novel Candidate Gene for Bone Mineral Density Variation and Fracture Risk Association

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations. Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL. Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively. Single-marker and haplotype analyses revealed that ESR2 and latent TGF-beta binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P=0.0004) and prevalent fracture (P=0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture. Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture.

A whole genome linkage scan for QTLs underlying peak bone mineral density

We conducted a whole genome linkage scan for quantitative trait loci (QTLs) underlying peak bone mineral density (PBMD). Our efforts identified several potential genomic regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation. Peak bone mineral density (PBMD) is an important clinical risk predictor of osteoporosis and explains a large part of bone mineral density (BMD) variation. To detect susceptive quantitative trait loci (QTLs) for PBMD variation including consideration of epistatic and sex-specific effects, we conducted a whole genome linkage scan (WGLS) for PBMD using 2,200 Caucasians from 207 pedigrees, aged 20-50 years. All the individuals were genotyped with 410 microsatellite markers. In addition to WGLS in the total combined sample of males and females, we conducted epistatic interaction analyses, and sex-specific subgroup linkage analyses. We identified several potential genomic regions that met the criteria for suggestive linkage. The most impressing region is 12p12 for hip PBMD (LOD = 2.79) in the total sample. Epistatic interaction analyses found a significant epistatic interaction between 12p12 and 22q13 (p = 0.0021) for hip PBMD. Additionally, we detected suggestive linkage evidence at 15q26 (LOD = 2.93), 2p13 (LOD = 2.64), and Xq27 (LOD = 2.64). Sex-specific analyses suggested the presence of sex-specific QTLs for PBMD variation. Our efforts identified several potential regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.

Association between myostatin gene polymorphisms and peak BMD variation in Chinese nuclear families

We identified 17 polymorphisms in myostatin by sequencing, and three informative single nucleotide polymorphisms (SNPs) were selected for further observation for their association with peak BMD of women in 401 Chinese nuclear families. Our results suggest that genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women. Myostatin is a TGF-beta family member that is a negative regulator of skeletal muscle growth. We identified SNPs in myostatin by direct sequencing. Furthermore, using a quantitative transmission disequilibrium test (QTDT). we tested and further test whether SNPs were associated with peak bone mineral density (BMD) variation at the spines and hips of 401 Chinese nuclear families. We identified 17 polymorphisms in myostatin by sequencing. Next, we selected three informative SNPs for further observation of an association with peak BMD of premenopausal women in 401 Chinese nuclear families. Using QTDT for the within-family association, we found significant association between rs2293284 and total hip, femoral neck, and trochanter BMD (all p < 0.05), while rs7570532 was associated with total hip and trochanter BMD (p = 0.034 and p = 0.035, respectively). The within-family association was significant between BMI and +2278G > A (p = 0.022). Subsequent permutations were in agreement with these significant within-family association results. Moreover, analyses of the haplotypes confer further evidence for association of rs2293284 and rs7570532 with hip peak BMD variation. These results suggest, for the first time, the genetic polymorphisms in myostatin likely play a role in attainment of peak BMD in Chinese women.

Physical Activity, Cdx-2 Genotype, and BMD

The present study investigated the interaction between Cdx-2 polymorphism and physical activity level over bone mineral density (BMD) variation in Brazilian postmenopausal women. One hundred and ninety women volunteered to participate in the study (66.6 +/- 5.3 years, 64.58 +/- 11.74 kg and 151.94 +/- 6.36 cm). Physical activity level (PAL) was assessed using the international physical activity questionnaire (IPAQ). Lumbar spine (L2 - L4), femoral neck, great trochanter and Wards' triangle bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DXA). The Cdx-2 polymorphism was genotyped by minisequencing, using the SNaPshottrade mark Multiplex System (Applied Biosystems, Foster City, CA, USA). Overall, no significant association was found between Cdx-2 polymorphism and adjusted BMD at any site. However, the results revealed a significant interaction between PAL and Cdx-2 genotype on adjusted femoral neck and Wards' triangle BMD. Active women carrying the Cdx-G/G genotype showed higher adjusted femoral neck and Wards' triangle BMD than inactive women carrying the same genotype, thus suggesting a larger chronic response to physical activity. These results suggest that, in postmenopausal women, the Cdx-2 polymorphism does not influence BMD by itself; however, it seems to affect the BMD response to physical activity since only the Cdx-G/G genotype carriers presented significant differences between active and inactive.

AHSG gene polymorphisms are associated with bone mineral density in Caucasian nuclear families

To investigate the role of alpha2-HS glycoprotein (AHSG) gene on bone mineral density (BMD) variation. A total of 665 subjects from 157 Caucasian nuclear families were genotyped at the AHSG NlaIII, SacI sites. The association and linkage between the single SNP markers and haplotypes constructed by two markers in this gene and BMDs at the spine and hip were determined by using quantitative transmission disequilibrium test (QTDT). Significant within-family associations were obtained for spine BMD at both of studied markers (P = 0.036 and 0.005 at the NlaIII and SacI sites, respectively). Significant (P = 0.008 at the NlaIII locus) (P = 0.004 at the SacI locus) total associations at spine BMD were detected. Haplotype analyses confirmed those within-family and total association. These data suggest the polymorphisms in the AHSG gene may have effects on BMD variation in Caucasian population.

Regionally specific compensation for bone loss in the tibial trabeculae of estrogen-deficient rats

Bone mineral density (BMD) and microstructural variations have been extensively investigated in recent years; however, the compensation for bone loss between different regions is still unclear. To fully characterize regional variations in bone mineral density (BMD) as well as the microstructure and dynamic changes of rat tibial trabeculae that occur with bone loss associated with estrogen deficiency. Female Sprague-Dawley rats were ovariectomized (OVX), sham-operated (sham), or left unoperated (baseline control). The left tibiae were harvested at baseline, and at postoperative weeks 3 and 15. High-resolution micro-computed tomography (microCT) was used to identify the densitometric and microstructural properties of trabeculae in the proximal ends of the rat tibia, specifically the epiphysis and metaphysis. Volumetric BMDs at the organ (organ BMD) and tissue (tissue BMD) levels were significantly higher for trabeculae at the epiphysis than metaphysis. Moreover, trabeculae at the epiphysis were thicker, and fewer in number and connectivity than those at the metaphysis, which were more rod like. Trabeculae at the metaphysis were more susceptible to bone loss induced by estrogen deprivation than at the epiphysis, and the regions varied greatly in their adaptation to this loss. At the metaphysis, trabecular tissue BMD and thickness were unexpectedly higher at postoperative week 15 than week 3 or baseline. In contrast, at the epiphysis, tissue BMD did not change with time, but trabecular thickness significantly increased at week 15 compared to baseline and was also greater in OVX compared to sham rats. Metaphyseal and epiphyseal trabeculae show regionally specific variations in BMD and microstructure. The former are more susceptible to bone loss induced by estrogen deficiency and would be strengthened by either hypertrophy or hypermineralization, while epiphyseal trabeculae are mainly strengthened by thickening.

Association between SNP and haplotypes in PPARGC1 and adiponectin genes and bone mineral density in Chinese nuclear families

To assess the contribution of single nucleotide polymorphisms (SNP) and haplotypes in the peroxisome proliferators-activated receptor-gamma co-activator-1 (PPARGC1) and adiponectin genes to normal bone mineral density (BMD) variation in healthy Chinese women and men. We performed population-based (ANOVA) and family-based (quantitative trait locus transmission disequilibrium test) association studies of PPARGC1 and adiponectin genes. SNP in the 2 genes were genotyped. BMD was measured using dual-energy X-ray absorptiometry in the lumbar spine and hip in 401 nuclear families with a total of 1260 subjects, including 458 premenopausal women, 20-40 years of age; 401 postmenopausal women (mothers), 43-74 years of age; and 401 men (fathers), 49-76 years of age. Significant within-family association was found between the Thr394Thr polymorphism in the PPGAGC1 gene and peak BMD in the femoral neck (P=0.026). Subsequent permutations were in agreement with this significant within-family association result (P=0.016), but Thr394Thr SNP only accounted for 0.7% of the variation in femoral neck peak BMD. However, no significant within-family association was detected between each SNP in the adiponectin gene and peak BMD. Although no significant association was found between BMD and SNP in the PPARGC1 and adiponectin genes in both men and postmenopausal women, haplotype 2 (T-T) in the adiponectin gene was associated with lumbar spine BMD in postmenopausal women (P=0.019). Our findings suggest that Thr394Thr SNP in the PPARGC1 gene was associated with peak BMD in the femoral neck in Chinese women. Confirmation of our results is needed in other populations and with more functional markers within and flanking the PPARGC1 or adiponectin genes region.

The Human Calcium-Sensing Receptor and Interleukin-6 Genes are Associated with Bone Mineral Density in Chinese

Calcium sensing receptor (CASR) is a central factor involved in calcium metabolism. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in osteoclast differentiation. Thus, both CASR and IL-6 are important in bone and mineral metabolism and are prominent candidate genes for osteoporosis. The study aimed to test association and/or linkage between the CASR and IL-6 genes with bone mineral density (BMD) variation in a Chinese population. A cytosine-adenine ( CA) n repeat polymorphism in the CASR gene and the IL-6 gene was genotyped, respectively, in 1 263 subjects from 402 Chinese nuclear families. Employing tests implemented in the program QTDT (quantitative transmission disequilibrium tests), a significant total association of the CASR (CA) 12 allele ( P = 0.006) and (CA) 18 allele ( P = 0.02) with BMD at the femoral neck was found. For the IL-6 gene, significant within-family associations were found between the ( CA) 14 allele and BMD at the total hip ( P = 0.021), the femoral neck ( P = 0.041), and the intertrochanteric region ( P = 0.029). A significant linkage was also observed between IL-6 CA repeat polymorphism and BMD at the spine ( P = 0.001). The results suggest that the CASR gene and the IL-6 gene may have effects on BMD variation in Chinese.

Confirmation of linkage to chromosome 1q for spine bone mineral density in southern Chinese

Chromosome 1q has previously been linked to bone mineral density (BMD) variation in the general population in several genome-wide linkage studies in both humans and mouse model. The aim of present study is to replicate and fine map the QTL influencing BMD in chromosome 1q in southern Chinese. Twelve microsatellite markers were genotyped for a 57 cMu region in the chromosome 1q in 306 southern Chinese families with 1,459 subjects. Each of these families was ascertained through a proband with BMD Z-scores less than -1.3 at the hip or spine. BMD (g/cm2) at the L1-4 lumbar spine, femoral neck (FN), trochanter and total hip was measured by dual-energy X-ray absortiometry. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. Four markers (D1S2878, D1S196, D1S452, and D1S218) achieved a LOD score greater than 1.0 with spine BMD, with the maximum multipoint LOD score of 2.36 at the marker D1S196. We did not detect a LOD score greater than 1.0 for BMD at the FN, trochanter, or total hip in multipoint linkage analyses. Our results present the first evidence for the presence of an osteoporosis susceptibility gene on chromosome 1q in non-Caucasian subjects. Further analyses of candidate genes are warranted to identify QTL genes and variants underlying the variations of BMD in this region.

Identification of Two Sex-Specific Quantitative Trait Loci in Chromosome 11q for Hip Bone Mineral Density in Chinese

Background: Chromosome 11q has not only been found to contain mutations responsible for the several Mendelian disorders of the skeleton, but it has also been linked to bone mineral density (BMD) variation in several genome-wide linkage studies. Furthermore, quantitative trait loci (QTL) affecting BMD in inbred mice and baboons have been mapped to a region syntenic to human chromosome 11q. The aim of the present study is to determine whether there is a QTL for BMD variation on chromosome 11q in the Chinese population. Methods: Nineteen microsatellite markers were genotyped for a 75 c<Kapital>M</Kapital> region on 11q13-25 in 306 Chinese families with 1,459 subjects. BMD (g/cm²) was measured by DXA. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. Results: For women, a maximum LOD score of 1.62 was achieved at 90.8 cM on 11q21 near the marker D11S4175 for femoral neck BMD; LOD scores greater than 1.0 were observed on 11q13 for trochanter BMD. For men, a maximum LOD score of 1.57 was achieved at 135.8 cM on 11q24 near the marker D11S4126 for total hip BMD. Conclusion: We have not only replicated the previous linkage finding on chromosome 11q but also identified two sex-specific QTL that contribute to BMD variation in Chinese women and men.

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

BackgroundFragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown.MethodsWe performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm2, n = 319) and high (> 1.11 g/cm2, n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections.ResultsBased on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm2) and 138 females with high (>1.04 g/cm2) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD.ConclusionThis study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis.

Association between VDR &amp;lt;italic&amp;gt;Apa&amp;lt;/italic&amp;gt;I Polymorphism and Hip Bone Mineral Density Can Be Modified by Body Mass Index: A Study on Postmenopausal Chinese Women

Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR) gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD) variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age (P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However, the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI (P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.

Preservation of Bone Mineral Density of the Proximal Femur Following Hemisurface Arthroplasty

Bone mineral density of the proximal femur was measured in six patients who underwent hemisurface replacement for osteonecrosis of the femoral head. Bone mineral density values in operated and contralateral nonoperated hips were compared. In four patients who had sequential examinations, bone mineral density was compared over time. Average patient age was 34.6 years, average follow-up was 9.1 years, and mean follow-up of bone mineral density measurements was 6.6 years. Average bone mineral density variation was 0.0048 to -0.0264 g/cm2 per year in all five regions in nonoperated hips and -0.012 to -0.0300 g/cm2 in operated hips. These results support bone conservation and preservation with hemiresurfacing arthroplasty in young patients with osteonecrosis of the femoral head.

Gaucher disease and bone: Laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy

The usefulness of bone turnover markers in Gaucher disease is still unclear and their utility in monitoring the effects of enzyme replacement therapy (ERT) on bone metabolism has not yet been investigated exhaustively. Skeletal involvement seems to improve slowly during ERT, but only a few studies evaluating bone mineral density (BMD) changes during a long follow-up period have been reported. The aim of this study was to assess the efficacy of ERT on bone involvement in a group of 12 type I Gaucher disease (GD I) patients by monitoring biochemical indices of bone resorption/formation and BMD measured by dual energy x-ray absorptiometry (DEXA). Serum (calcium, phosphorus, bone alkaline phosphatase isoenzyme, carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin, intact parathyroid hormone) and urinary (calcium, phosphorus, hydroxyproline and free deoxypyridinoline) markers of bone metabolism and lumbar BMD were measured at baseline, after 6 and 12 months, and then every year for a mean ERT follow-up period of 4.5 years (range 4.4-6 years). Twelve healthy adult subjects matched for age and sex were tested as negative controls. A significant decrease of PICP was detected in the patient group at baseline (mean value 100.52 ng/ml vs 142.45 ng/ml, p = 0.017), while ICTP was remarkably higher: mean value 3.93 ng/ml vs 2.72 ng/ml, p = 0.004 (two-sided Student's t-test). No changes in bone formation indices were observed during the follow-up period, while urinary calcium excretion increased significantly from 0.065 to 0.191 mg/mg creatinine (p = 0.0014) (repeated measures ANOVA). A significant BMD improvement was also detected after an average ERT period of 4.5 years: Z-score increased from -0.81 to -0.56 (p = 0.005) (two-sided Student's t-test). These data evidenced the ineffectiveness of the biochemical markers used in monitoring ERT efficacy in GD I skeletal involvement, whereas DEXA was demonstrated to be a reliable method with which to follow up BMD improvement.

Grossesse et douleurs rhumatologiques lombaires basses et de la ceinture pelvienne

Prevalence and factors influencing pelvic joint and low-back pain during pregnancy are hereby reported. They can be associated with considerable disabilities as far as daily activities are concerned. They may be reduced by appropriate measures. Disc herniation rarely occurs during pregnancy and can be treated by oral or epidural steroid administration. Surgical intervention is scarcely indicated. In these cases MRI may be used, but only after the first trimester. Though uncommon, osteoporosis leading to vertebral or hip pain and fracture can occur during pregnancy and breastfeeding. Women concerned may have a pre-existing bone disease revealed by the physiological bone loss that occurs during pregnancy and breastfeeding. Other factors may influence bone mineral density variation such as osteomalacia, steroid or heparin administration. The relationship between transient osteoporosis of the hip and osteoporosis is discussed. Bone investigations and bone mineral density measurement after delivery are required.

Role of Vitamin D and Parathyroid Hormone in the Regulation of Bone Turnover and Bone Mass in Men: The MINOS Study

We investigated the role of vitamin D and of parathyroid hormone (PTH) in the regulation of bone mineral density (BMD), tone dimensions and seasonal variation of bone turnover in 881 men aged 19-85 years. Bone mineral content (BMC) and BMD of the lumbar spine, hip and whole body were measured with HOLOGIC 1000W and those of distal forearm with an OSTEOMETER DTX 100 device. Bone formation was evaluated using osteocalcin, bone alkaline phosphatase and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by 24-hour excretion of deoxypyridinoline and of C-terminal telopeptide of collagen type I. In young men (< 55 yrs) PTH level decreased with age (r = -0.18, P < 0.005) whereas 25-hydroxyvitamin D (25OHD) concentration was stable. In older men (> 55 years) 25OHD decreased whereas PTH increased with age (r = -0.27 and r = 0.21, P = 0.0001). In young men, 25OHD level varied with season but not PTH, biochemical markers of bone turnover nor BMD. In young men, 25OHD, but not PTH, was a significant determinant of BMC, cortical thickness and of biomechanical properties of the femoral neck. Biochemical bone markers and BMD were not correlated with PTH nor with 25OHD. In elderly men, winter levels of 25OHD were lowest whereas those of PTH, bone resorption markers and PINP were highest. After adjustment for age, body weight and season, biochemical markers of bone turnover were correlated with PTH. In elderly men, 25OHD and PTH were significant determinants of BMC, cortical thickness and of biomechanical parameters of the femoral neck. Men with vertebral deformities had lower concentrations of 25OHD, higher PTH levels and slightly elevated urinary excretion of biochemical markers of bone resorption compared with men without vertebral deformities. In conclusion, in young men, 25OHD discloses a seasonal variability in contrast to PTH and biochemical bone markers. In this group, 25OHD is a significant determinant of BMC and BMD but not of bone size. In elderly men, seasonal variation of 25OHD and PTH concentrations result in seasonal variation of bone resorption. In this group, both 25OHD and PTH are determinants of BMC and cortical thickness of the femoral neck and, consequently, of its mechanical parameters.