Genome-wide association study of bone mineral density trait among three pig breeds

Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e⁻¹⁴) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.     

Relation of common allelic variation at vitamin D receptor locus to bone mineral density and postmenopausal bone loss: cross sectional and longitudinal population study.

OBJECTIVE: To determine whether common allelic variation at the vitamin D receptor locus is related to bone mineral density and postmenopausal bone loss. DESIGN: Cross sectional and longitudinal population study. SETTING: Outpatient clinic in research centre. SUBJECTS: 599 healthy women aged 27 to 72 and 125 women with low bone mass aged 55-77 had bone mineral density measured once in the cross sectional study. 136 women aged 45-54 were followed up for 18 years in the longitudinal study. MAIN OUTCOME MEASURES: Bone mineral density measured at the lumbar spine, hip, and forearm and rate of bone loss at different times over 18 years in relation to vitamin D receptor genotype as defined by the endonucleases ApaI, EsmI, and TaqI. RESULTS: Vitamin D receptor genotype was not related to bone mineral density at any site. The maximum difference between homozygotes was 1.3% (P = 0.33, n = 723). Women with low bone mineral density had almost the same genotype frequencies as the women with normal bone mineral densities. Vitamin D receptor genotype was not related to early postmenopausal bone loss from age 51 to 53 (mean (SD) total loss at the lower forearm -3.6% (3.6%)), late postmenopausal bone loss from age 63 to 69 (at the hip-6.2% (8.7%)), or to long term postmenopausal loss from age 51 to 69 (at the lower forearm-24.5% (11.4%)). CONCLUSION: Common allelic variation at the vitamin D receptor locus as defined by the endonucleases ApaI, EsmI, and TaqI is related neither to bone mineral density nor to the rate of bone loss in healthy postmenopausal Danish women.     

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.     

A regulatory variant at 3q21.1 confers an increased pleiotropic risk for hyperglycemia and altered bone mineral density

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Genome-wide QTL mapping of nine body composition and bone mineral density traits in pigs

Background

Since the pig is one of the most important livestock animals worldwide, mapping loci that are associated with economically important traits and/or traits that influence animal welfare is extremely relevant for efficient future pig breeding. Therefore, the purpose of this study was a genome-wide mapping of quantitative trait loci (QTL) associated with nine body composition and bone mineral traits: absolute (Fat, Lean) and percentage (FatPC, LeanPC) fat and lean mass, live weight (Weight), soft tissue X-ray attenuation coefficient (R), absolute (BMC) and percentage (BMCPC) bone mineral content and bone mineral density (BMD).

Methods

Data on the nine traits investigated were obtained by Dual-energy X-ray absorptiometry for 551 pigs that were between 160 and 200 days old. In addition, all pigs were genotyped using Illumina’s PorcineSNP60 Genotyping BeadChip. Based on these data, a genome-wide combined linkage and linkage disequilibrium analysis was conducted. Thus, we used 44 611 sliding windows that each consisted of 20 adjacent single nucleotide polymorphisms (SNPs). For the middle of each sliding window a variance component analysis was carried out using ASReml. The underlying mixed linear model included random QTL and polygenic effects, with fixed effects of sex, housing, season and age.

Results

Using a Bonferroni-corrected genome-wide significance threshold of P < 0.001, significant peaks were identified for all traits except BMCPC. Overall, we identified 72 QTL on 16 chromosomes, of which 24 were significantly associated with one trait only and the remaining with more than one trait. For example, a QTL on chromosome 2 included the highest peak across the genome for four traits (Fat, FatPC, LeanPC and R). The nearby gene, ZNF608, is known to be associated with body mass index in humans and involved in starvation in Drosophila, which makes it an extremely good candidate gene for this QTL.

Conclusions

Our QTL mapping approach identified 72 QTL, some of which confirmed results of previous studies in pigs. However, we also detected significant associations that have not been published before and were able to identify a number of new and promising candidate genes, such as ZNF608.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-014-0068-2) contains supplementary material, which is available to authorized users.     

Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus

To identify genetic loci influencing bone accrual, we performed a genome-wide association scan for total-body bone mineral density (TB-BMD) variation in 2,660 children of different ethnicities. We discovered variants in 7q31.31 associated with BMD measurements, with the lowest P = 4.1 × 10(-11) observed for rs917727 with minor allele frequency of 0.37. We sought replication for all SNPs located ± 500 kb from rs917727 in 11,052 additional individuals from five independent studies including children and adults, together with de novo genotyping of rs3801387 (in perfect linkage disequilibrium (LD) with rs917727) in 1,014 mothers of children from the discovery cohort. The top signal mapping in the surroundings of WNT16 was replicated across studies with a meta-analysis P = 2.6 × 10(-31) and an effect size explaining between 0.6%-1.8% of TB-BMD variance. Conditional analyses on this signal revealed a secondary signal for total body BMD (P = 1.42 × 10(-10)) for rs4609139 and mapping to C7orf58. We also examined the genomic region for association with skull BMD to test if the associations were independent of skeletal loading. We identified two signals influencing skull BMD variation, including rs917727 (P = 1.9 × 10(-16)) and rs7801723 (P = 8.9 × 10(-28)), also mapping to C7orf58 (r(2) = 0.50 with rs4609139). Wnt16 knockout (KO) mice with reduced total body BMD and gene expression profiles in human bone biopsies support a role of C7orf58 and WNT16 on the BMD phenotypes observed at the human population level. In summary, we detected two independent signals influencing total body and skull BMD variation in children and adults, thus demonstrating the presence of allelic heterogeneity at the WNT16 locus. One of the skull BMD signals mapping to C7orf58 is mostly driven by children, suggesting temporal determination on peak bone mass acquisition. Our life-course approach postulates that these genetic effects influencing peak bone mass accrual may impact the risk of osteoporosis later in life.     

The effect of restriction of dietary calcium on trabecular and cortical bone mineral density in the rats

This study aimed to investigate effects of restricted calcium intake on cortical and trabecular bone density in white rats. Low Ca diet was fed for six weeks, and bone density and bone metabolism parameters were assessed in blood. This study was carried out on 12 male white rats aged 12 weeks (Sprague-Dawley; SD). These rats were bred for 1 week and randomly assigned to the standard calcium diet group (SCa group, n = 6) and the low calcium diet group (LCa group; n = 6). The SCa group was given a modified AIN-93M mineral mix (with 0.5% Ca), which was made by adding calcium to a standard AIN93 diet, and the LCa Group was fed a modified AIN-93 Mineral mix (with 0.1% Ca). Femoral BMD and BMC were measured by DEXA in each rat. After trabecular bone was separated from cortical bone, volumetric bone mineral density (vBMD) was measured using pQCT. Serum Ca and P levels were measured as parameters of bone metabolism, and S-ALP, S-TrACP and-Dpd levels were also measured. The results revealed no significant differences in weight, growth rate, feed consumption and feed efficiency between the two groups before and after calcium-restricted diet (p > .05). No significant differences were also observed in bone length and bone mass between the two groups (p > .05). Although bilateral femoral BMDs were not significantly different between the two groups, bilateral femoral BMCs significantly decreased in the LCa group, compared with the SCa group (p = .023, p = .047). Bilateral cortical MDs were not significantly different between the two groups, either. However, trabecular BMD significantly decreased in the LCa group, compared with the SCa group (p = .041). U-Dpd and S-TrACP levels significantly declined in the LCa group, compared to the SCa group (p = .039, p = .010). There were no significant differences in serum Ca and P levels between the two groups (p > .05). However, a significant decrease in urinary Ca level (p = .001) and a significant increase in urinary P (p = .001) were observed in the LCa group, compared to the Sca group. These findings described that six-week low calcium diet led to decreased trabecular bone density, reduced urinary excretion of Ca and increased urinary excretion of P. As a result, Ca hemeostasis can be maintained.     

Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita

Two polymorphic dinucleotide repeats--one (dGdA)n and one (dGdT)n--have been identified at the SCN4A locus, encoding the alpha-subunit of the adult skeletal muscle sodium channel. When typed using PCR, the dinucleotide repeats display 4 and 10 alleles, respectively, with a predicted heterozygosity of .81 for the combined haplotype. We have applied these polymorphisms to the investigation of hyperkalemic periodic paralysis and paramyotonia congenita, distinct neuromuscular disorders both of which are thought to involve mutation at SCN4A. Our data confirm the genetic linkage of both disorders with SCN4A. Haplotype analysis also indicates the strong likelihood of allelic heterogeneity in both disorders.     

Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men

In order to assess the contribution of polymorphisms in the RANKL (TNFSF11), RANK (TNFRSF11A) and OPG (TNFRSF11B) genes to variations in bone mineral density (BMD), a population-based cohort with 1,120 extreme low hip BMD cases or extreme high hip BMD controls was genotyped on five SNPs. We further explored the associations between these genetic variations and forearm BMDs by genotyping 266 offspring and 309 available parents from 160 nuclear families. A family-based association test was used. Significantly positive associations were found for A163G polymorphisms in the promoter regions of the OPG gene, a missense substitution in exon 7 (Ala192Val) of the RANK gene and rs9594782 SNP in the 5′ UTR of the RANKL gene with BMD in men only. Men with TC/CC genotypes of the rs9594782 SNP had a 2.1 times higher risk of extremely low hip BMD (P=0.004), and lower whole body BMD (P<0.001). Subjects with the TC genotype of the Ala192Val polymorphism had a 40% reduced risk of having extremely low hip BMD (P<0.01), and higher whole body BMD (P<0.01). Subjects with the GG genotype of the A163G polymorphism had a 70% reduced risk of having extremely low hip BMD (P<0.05), and higher whole body BMD (P<0.01). Significant gene–gene interactions were also observed among the OPG, RANK and RANKL genes. Our findings suggest that genetic variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are strongly associated with BMD at different skeletal sites in adult men, but not in women. Electronic Supplementary Material Supplementary material is available for this article at     

Familial comparison of bone mineral density at the proximal femur and lumbar spine

Familial resemblance of bone mineral density (BMD) was studied in the lumbar spine and three regions of the proximal femur in 41 biological mother-daughter (M-D), 42 mother-son (M-S), 24 mother-grandmother (M-G) pairs and 18 mother-grandmother-daughter (M-G-D) triads. Children were placed into three maturity categories based on an assessment of secondary sex characteristics and growth velocities. Two sets of standardized BMD Z-scores were derived for the children based on either their chronological age or their maturational status. These scores were compared with maternal Z-scores derived from age-specific norms. Similar comparisons were made between the Z-scores of the mothers and grandmothers. For all three regions of the proximal femur and for the total AP lumbar spine the correlations between Z-score values were similar and significant (P < 0.05) between the M-G and M-D pairs ranging from 0.41 to 0.57. In general, the familial correlations improved when maturity-status based Z-scores were used for comparison. The absolute BMD values measured in the grandmothers and the three maturity groups of the children — expressed as a percentage of the BMD of the mothers — showed that at the neck and the trochanteric regions of the proximal femur the late-pubescent girls and boys had a significantly (P < 0.05) greater bone density than their mothers (115–123%), whereas at the AP spine these groups averaged only 88% of their mothers BMD. This site differential was not apparent when comparing the post-menopausal grandmothers with the pre-menopausal mothers (80% at both sites). Three generation comparisons demonstrated a strong familial resemblance in bone mineral density. The value of incorporating maturity-based versus chronological-based parameters for comparison with adult measures in studies that involve growing children at different stages of development was also demonstrated.     

Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet.

Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.     

Effects of physical training on bone mineral density and bone metabolism

The purpose of this study was to examine the influences of long-term walking training and walking and jumping training on bone mineral density (BMD) and bone metabolism. Data from 28 healthy premenopausal women was assessed. The subjects were divided into the walking group (WG; 17 women mean+/-SE age 35+/-2 years), and the walking and jumping group (WJG; 11 women mean+/-SE age 39+/-1 years). BMD was measured in the lumbar spine and proximal femur using dual energy X-ray absorptiometry (DXA). As markers of bone metabolism, this study was to measure bone formation markers, bone-alkaline phosphatase (B-ALP: measured by enzyme immunoassay/EIA) and osteocalcin (BGP: by radioimmunoassay/RI) as well as bone resorption markers, parathyroid hormone (PTH: measured by/RI) and type I collagen cross-linked N-telopeptides (NTx: by EIA). Despite the significant decrease in body weight (p<0.05), no corresponding decrease in BMD was observed. Moreover, no significant difference in bone markers BGP, PTH, and NTx was observed. B-ALP was significantly increased (p<0.05) after one year, and the rate of this increase was greater in the WJG than in the WG. It is thus concluded that walking training for one year is beneficial for the promotion of bone formation, and that jumping stimulus maintain BMD effectively.     

The effects of weight loss on relative bone mineral density in premenopausal women

Objective:

This study compared BMD relative to body weight following a ～6‐month weight loss program and a 1‐year weight maintenance phase in premenopausal women and determined whether African American (AA) and European‐American (EA) women's BMD respond similarly during weight loss.

Design and Methods:

Premenopausal women (n = 115, 34 ± 5 years) were evaluated in an overweight state (BMI between 27 and 30 kg/m²), following an 800 kcal/day diet/exercise program designed to reduce BMI<25 kg/m², and 1‐year following weight loss.

Results:

BMD relative to body weight (Z‐scores) increased after weight loss, but decreased during the 1‐year weight maintenance phase. All 1‐year follow‐up BMD Z‐scores were increased (except L1) compared to baseline measurements (P < 0.05). These sites included the hip neck (+0.088, P = 0.014), total hip (+0.099, P = 0.001), L2 (+0.127, P = 0.013), L3 (+0.135, P = 0.014), and L4 (+0.199, P = 0.002). AAs had significantly higher absolute BMD at all sites (P < 0.05) compared to EAs, but no time by race interactions were evident during weight loss (except in L3).

Conclusion:

These results may indicate that weight loss is safe with regard to bone health for overweight premenopausal women.     

Variable pleiotropic effects from mutations at the same locus hamper prediction of fitness from a fitness component

The relationship of genotype, fitness components, and fitness can be complicated by genetic effects such as pleiotropy and epistasis and by heterogeneous environments. However, because it is often difficult to measure genotype and fitness directly, fitness components are commonly used to estimate fitness without regard to genetic architecture. The small bacteriophage X174 enables direct evaluation of genetic and environmental effects on fitness components and fitness. We used 15 mutants to study mutation effects on attachment rate and fitness in six hosts. The mutants differed from our lab strain of X174 by only one or two amino acids in the major capsid protein (gpF, sites 101 and 102). The sites are variable in natural and experimentally evolved X174 populations and affect phage attachment rate. Within the limits of detection of our assays, all mutations were neutral or deleterious relative to the wild type; 11 mutants had decreased host range. While fitness was predictable from attachment rate in most cases, 3 mutants had rapid attachment but low fitness on most hosts. Thus, some mutations had a pleiotropic effect on a fitness component other than attachment rate. In addition, on one host most mutants had high attachment rate but decreased fitness, suggesting that pleiotropic effects also depended on host. The data highlight that even in this simple, well-characterized system, prediction of fitness from a fitness component depends on genetic architecture and environment.     

A congenic mouse and candidate gene at the Chromosome 13 locus regulating bone density

Previously, we identified two significant quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected for bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains, SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. We recently designated the Chr 13 locus as Pbd2 (Peak bone density 2) and constructed a congenic strain, P6.P2-Pbd2(b), which carried a single genomic interval from the Chr 13 of SAMP2 on a SAMP6-derived osteoporotic background. In this study, we have constructed a congenic strain, P2.P6-Pbd2(a), carrying a SAMP6-derived susceptible interval on a SAMP2-derived resistance background. This congenic strain had a lower bone density than the background strain, SAMP2, based on three measurement methods, each utilizing a different principle for evaluating bone density: MD, DXA, and pQCT. Next, a candidate gene approach was used to find polymorphisms of Bmp6 (bone morphogenetic protein 6). The CAG trinucleotide repeat numbers in exon 1 of this gene differ among SAM strains. We found an association of CAG repeat length with relative peak bone mass in mice.     

Relation of bone mineral density and content to mineral content and density of the fat-free mass.

Differences in the mineral fraction of the fat-free mass (M(FFM)) and in the density of the FFM (D(FFM)) are often inferred from measures of bone mineral content (BMC) or bone mineral density (BMD). We studied the relation of BMC and BMD to the M(FFM) and D(FFM) in a heterogeneous sample of 216 young men (n = 115) and women (n = 101), which included whites (n = 155) and blacks (n = 61) and collegiate athletes ( n = 132) and nonathletes (n = 84). Whole body BMC and BMD were determined by dual-energy X-ray absorptiometry (DXA; Hologic QDR-1000W, enhanced whole body analysis software, version 5.71). FFM was estimated using a four-component model from measures of body density by hydrostatic weighing, body water by deuterium dilution, and bone mineral by DXA. There was no significant relation of BMD to M(FFM) (r = 0.01) or D(FFM) (r = -0.06) or of BMC to M(FFM) (r = -0.11) and a significant, weak negative relation of BMC to D(FFM) (r = -0.14, P = 0.04) in all subjects. Significant low to moderate relationships of BMD or BMC to M(FFM) or D(FFM) were found within some gender-race-athletic status subgroups or when the effects of gender, race, and athletic status were held constant using multiple regression, but BMD and BMC explained only 10-17% of the variance in M(FFM) and 0-2% of the variance in D(FFM) in addition to that explained by the demographic variables. We conclude that there is not a significant positive relation of BMD and BMC to M(FFM) or D(FFM) in young adults and that BMC and BMD should not be used to infer differences in M(FFM) or D(FFM).     

Effect of mineral dissolution from bone specimens on the viscoelastic properties of cortical bone

Although physiological saline (0.15 M NaCl aqueous solution) has been used as a storage solution to prevent bone specimens from drying, there have been reports that Ca²⁺ ions dissolve from bone specimens during the storage in saline. In order to determine whether such storage has a marked effect on mechanical properties, the relaxation modulus of bovine cortical bone stored in physiological saline was compared with that stored in a buffer solution containing a sufficient amount of Ca²⁺ ions. After storage in saline, the modulus value of specimens was significantly reduced from that before storage. On the other hand, the modulus value of specimens soaked in the solution containing sufficient Ca²⁺ ions did not change after storage. The relaxation rate of a bone specimen stored in physiological saline was larger than that of a specimen stored in Ca²⁺-buffered saline solution and that of the control specimens. The results suggest that by the dissolution of Ca²⁺ ions from a bone specimen during storage in physiological saline, percolated paths of mineral phase and of reinforced matrix phase are disjoined, resulting in reduction in the elastic modulus and change in the viscoelastic properties of bone.     

Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density,fractures, and syndesmophytes

Introduction

Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.

Methods

High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.

Results

The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (r_S = 0.762; P < 0.001), and tibia (r_S = 0.712; P < 0.001).When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016).mSASSS correlated negatively with trabecular vBMD in lumbar spine (r_S = -0.620; P < 0.001), radius (r_S = -0.400; p = 0.001) and tibia (r_S = -0.475; p < 0.001) and also with trabecular thickness in radius (r_S = -0.528; P < 0.001) and tibia (r_S = -0.488; P < 0.001).Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (r_S = 0.636; P < 0.001).

Conclusions

Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.