Higher BMD Research Articles

Knee osteoarthritis is associated with increased prevalence of vertebral fractures despite high systemic bone mineral density: a cross-sectional study in an Asian population

ObjectivesThis study aimed to evaluate the relationship between radiographic knee osteoarthritis and vertebral fractures (VFs) in an Asian population.MethodsThis cross-sectional study involved data from 1,829 participants of the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee osteoarthritis was defined as Kellgren–Lawrence (KL) grades ≥2. Prevalent VF was defined as a loss of ≥4 cm of height from the peak height. BMD was measured using dual-energy X-ray absorptiometry, in the lumbar spine and femoral neck.ResultsIn both sexes, the prevalence of VFs increased with age, and was higher in the knee osteoarthritis group than in the control group (in men 13.2 % in osteoarthritis group and 7.9 % in control group; in women 27.7 % in osteoarthritis group and 14.7 % in control group). Age-adjusted BMD at the lumbar spine and femoral neck was significantly higher in the knee osteoarthritis group. In multivariable analysis, KL grade 4 was significantly associated with vertebral fractures in men. In women, there was a significant trend for a positive association between KL grades and vertebral fractures.ConclusionsDespite high systemic BMD, knee osteoarthritis was positively associated with VFs. These results suggest that bone quality, and consequently bone strength, may be decreased at the systemic level in knee osteoarthritis.

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.

Changes in Bone Quality of the Femoral Diaphysis Induced by High-Level Fluorine Ingestion in Ovariectomized Rats

Ovariectomized rats were fed a diet containing minerals at high concentrations, such as Ca, P, and F (high-mineral diet), and changes in the femoral diaphysis were investigated after 24 weeks. The femur was mainly red and partially orange on the color scale of the 3D-map in Groups A and B, showing a high BMD. The region adjacent to the marrow cavity was yellow, showing a lower BMD than that in the outer region of the femur. In Group C, the red area was small in the outer region and the inner region was mainly yellow and green on the color scale. The inner region adjacent to the marrow cavity showed a view of unevenly resorbed bone, and the BMD was lower than those in Groups A and B. Incorporation of F into the body influences the apatite crystal structure and crystal growth, which subsequently influences adsorption of F to crystals and structural changes. Therefore, it is important to ingest F at the optimum concentration.

Polymorphisms in the Inflammatory Genes CIITA, CLEC16A and IFNG Influence BMD, Bone Loss and Fracture in Elderly Women

Osteoclast activity and the fine balance between bone formation and resorption is affected by inflammatory factors such as cytokines and T lymphocyte activity, mediated by major histocompatibility complex (MHC) molecules, in turn regulated by the MHC class II transactivator (MHC2TA). We investigated the effect of functional polymorphisms in the MHC2TA gene (CIITA), and two additional genes; C-type lectin domain 16A (CLEC16A), in linkage disequilibrium with CIITA and Interferon-γ (IFNG), an inducer of CIITA; on bone density, bone resorption markers, bone loss and fracture risk in 75 year-old women followed for up to 10 years (OPRA n = 1003) and in young adult women (PEAK-25 n = 999). CIITA was associated with BMD at age 75 (lumbar spine p = 0.011; femoral neck (FN) p = 0.049) and age 80 (total body p = 0.015; total hip p = 0.042; FN p = 0.028). Carriers of the CIITA rs3087456(G) allele had 1.8–3.4% higher BMD and displayed increased rate of bone loss between age 75 and 80 (FN p = 0.013; total hip p = 0.030; total body p = 3.8E−5). Despite increasing bone loss, the rs3087456(G) allele was protective against incident fracture overall (p = 0.002), osteoporotic fracture and hip fracture. Carriers of CLEC16A and IFNG variant alleles had lower BMD (p<0.05) and ultrasound parameters and a lower risk of incident fracture (CLEC16A, p = 0.011). In 25-year old women, none of the genes were associated with BMD. In conclusion, variation in inflammatory genes CIITA, CLEC-16A and INFG appear to contribute to bone phenotypes in elderly women and suggest a role for low-grade inflammation and MHC class II expression for osteoporosis pathogenesis.

Determinants of bone mineral density in postmenopausal women in Northern Ireland

Model 1 explained 37 % of the variance in total body T-score, F (4, 253) = 39.43, p < 0.001. Model 2 explained a further 3 % of the variance, F (11, 246) = 16.28, p < 0.001. Model 3 explained a further 1 % of the variance, F (15, 242) = 13.00, p < 0.001. The main variables which explained most of the variance in total body T score were increasing age, which was associated with lower BMD ( b= - 0.26; p = 0.001), higher percentage body fat, which was associated with higher BMD ( b= 0.225; p = 0.048), higher fat free mass (FFM), which was associated with higher BMD ( b= 0.385; p < 0.001) and current smoking which was negatively associated with BMD ( b= - 0.163; p = 0.001). Within this cohort, BTM did not explain any of the variance in BMD, albeit the obvious risk factors of increasing age and smoking were associated with a lower total body BMD, whereas weight (FM and FFM) were associated with a higher BMD. Similar findings have been reported recently by others (4,5) . In conclusion, findings from this study indicate that there is a relationship between FFM and BMD, suggesting that muscle weight has an additional predictive value over fat mass and, together with exercise, may potentially help to prevent osteoporosis.

The Relationship between Bone Mineral Density and Dietary Intake in Moroccan Children with Juvenile Idiopathic Arthritis

Background and objective: The aim of this study was to evaluate the association between dietary intake and bone mineral density in children with juvenile idiopathic arthritis (JIA). Methods: A cross-sectional study carried out in Morocco between May 2010 and June 2011, covering out patients with JIA. The characteristics of patients were collected. The nutritional status was assessed by a food questionnaire including data of food intake during 7 consecutive days using 24-hour dietary recall. Food intake was quantified using the software Bilnut (Bilnut version 2.01, 1991). Bone mineral density (BMD in g/cm2) was measured by DXA method (X-ray absorptiometry) on a Lunar Prodigy. Results: The study consisted of 33 patients with JIA (4 - 16 years old). The median age of patients was 10.4 ± 4.3 years. Median disease duration was 2 (1 - 4.5) years. The group of patients with low dietary intake of proteins was associated with low BMD (p = 0.03). Low BMD was related with low intake of magnesium (p = 0.007) and vitamin C (p = 0.04) in children aged between 4 and 9 years. Low intake of vitamin E and folate was associated with high BMD in the other range of children (p < 0.001). Conclusion: This study suggests that low intake of protein and of some micronutrients (magnesium, vitamin C, vitamin E and folate) influence bone mass in children with JIA. Prospective studies with a larger number of patients seem to be necessary in order to confirm our findings.

성인 남성에서 5년간의 골밀도 변화 관찰

성인 남성들이 2002년부터 2006년 까지 건강검진을 받기위해 대학병원을 내원한 성인 남성 80명을 개인별 골밀도를 5년간 관찰하여 분석하였다. 연구 대상자 성인 남성 80명의 평균연령은 <TEX>$43.15{\pm}4.82$</TEX>세였다. 대퇴경부의 골밀도는 1차 측정에서 -0.61에 비하여 4차 및 5차 측정에서 유의하게 감소하였으며, 척추 골밀도는 1차 측정 -0.67에서 2차 측정에서 유의한 감소를 나타냈지만 3~5차 측정에서 유의한 차이를 보이지 않았다. 생활습관에 따른 음주, 흡연, 운동, 식습관에 따른 군 간의 대퇴경부 및 척추 골밀도 변화 값의 차이는 보이지 않았다. 1차 측정에서의 대퇴경부 골밀도를 기준으로 골밀도 상(<TEX>$0{\leqq}BMD$</TEX>), 중(<TEX>$-1.0{\leqq}BMD</TEX><TEX><</TEX><TEX>0$</TEX>), 하(BMD < -1.0) 집단에서 1차 측정과 5차 측정 골밀도의 차이를 비교하였을 때, 상 집단에서 대퇴경부 골밀도가 1차 <TEX>$0.67{\pm}0.76$</TEX>에서 <TEX>$0.42{\pm}0.93$</TEX>로 유의하게 감소하였다. 다른 집단에서는 전후 비교에서 유의한 차이를 보이지 않았다. 대상자들의 나이에 관계없이 젊어서부터 골밀도가 낮은 사람들은 대퇴경부 및 척추의 골밀도가 낮아 있었으며, 골밀도가 높은 사람들은 1차 측정 때부터 5차 측정 때까지 높았다. 대퇴경의 골밀도는 1차 측정에 비해 5차에서 유의한 감소를 나타내어 척추보다는 대퇴경부의 골밀도에 주의하도록 한다. To investigate the decrease of BMD by age and the risk factor of osteoporosis in Korean men. We describe the study of a five-years retrospective observational study with male patients. Eighty Korean men who visited hospital for health screening were assessed for this study from 2002 to 2006. We evaluated the BMD of the femoral neck and L-spine, and the preferences and habits in the life. The data were collected for 5 years, and we analysed the five-years change of BMD and the relations between BMD and other factors. Subjects were divided into 3 group by 1st assessment of femoral neck BMD, and were compared with each other. The age of subjects was <TEX>$43.15{\pm}4.82$</TEX> and BMD of femoral neck was <TEX>$-0.61{\pm}0.97$</TEX> and BMD of L-spine was <TEX>$-0.67{\pm}1.10$</TEX> in the first year assessment. The femoral neck BMD of 4th and 5th assessment was decreased significantly compared to that of 1st assessment. The L-spine BMD of 2nd assessment was decreased significantly compared to the 1st assessment. There was no significant correlation between the changes of BMD and preferences or habits-drinking, smoking, eating habit, exercise. The femoral neck BMD of 5th assessment was decreased significantly compared to that of 1st assessment in the high femoral neck BMD group. And there was no significant change of femoral BMD and L-spine BMD in other groups. Low BMD group in the 1st assessment showed lowest BMD in the 5th assessment and high BMD group in the 1st assessment showed highest BMD in the 5th assessment. We can guess that the young men who has low BMD could have high risk of osteoporosis when he became older. And the femoral BMD should be considered important in anticipating the changes of BMD in middle aged men.

The effect of physical activity on bone mineral density

The purpose of this study was to find out the physical activity levels of females studying at university and to examine the relation between their physical activity levels and bone mineral densities. 63 female students who study at Nigde University participated in the study. 32 of them have low physical activity levels while 31 of them have high physical activity levels. In the study, a short form of International Physical Activity Questionnaire was used to determine the physical activity levels of the individuals. T-test in independent groups was used to find out the difference between the groups. The relation between bone mineral densities, body composition and physical activity levels was determined by Pearson correlation test. According to the data obtained in the study, a significant difference was found between the fatless body mass, physical activity levels, BMD, t-scores and z-scores of the participants while no significant difference was found in BMI, body fat rate and body fat mass values. In terms of physical activity levels, it was found out that there is a relation between those with high physical activity levels and BMD, t-scores, z-scores, and also a relation between those with low physical activity levels and fatless body mass. The results of the study have revealed that females with high physical activity levels also have high bone mineral densities, showing a direct proportion between physical activity level and bone mineral density. Key words: Physical activity, bone mineral densities, body fat mass, body fat rate.

P1-369 The association between oral contraceptive use and bone mass in both young and older women

IntroductionThe association between oral contraceptive use and bone mass remains inconclusive.AimTo describe the associations between current and ever use of OC, bone mass and vertebral deformity in population-based samples of...

An integrative study ascertained SOD2 as a susceptibility gene for osteoporosis in Chinese.

Osteoporosis is characterized by low BMD and has strong genetic determination. However, specific genetic variants influencing BMD and contributing to the pathogenesis of osteoporosis are largely uncharacterized. Current genetic studies in bone, which are aimed at identification of osteoporosis risk genes, are focused mostly on DNA, RNA, or the protein level individually, lacking integrative evidence from the three levels of genetic information flow to confidently ascertain the significance of genes for osteoporosis. Our previous proteomics study discovered that superoxide dismutase 2 (SOD2) in circulating monocytes (CMCs, ie, potential osteoclast precursors) was significantly upregulated at protein level in vivo in Chinese with low versus high hip BMD. Herein, at mRNA level, we found that SOD2 gene expression also was upregulated in CMCs (p < 0.05) in Chinese with low versus high hip BMD. At the DNA level, in 1627 unrelated Chinese subjects, we identified eight single-nucleotide polymorphisms (SNPs) at the SOD2 gene locus that were suggestively associated with hip BMD (peak signal at rs11968525, p = 0.048). Among the eight SNPs, three SNPs (rs7754103, rs7754295, and rs2053949) were associated with the SOD2 mRNA expression level (p < 0.05), suggesting that they are expression quantitative trait loci (eQTLs) regulating SOD2 gene expression. In conclusion, this integrative evidence from DNA, RNA, and protein levels support SOD2 as a susceptibility gene for osteoporosis.

Combined effects of recombinant human BMP-2 and Nell-1 on bone regeneration in rapid distraction osteogenesis of rabbit tibia

Distraction osteogenesis (DO) has been accepted as an effective technique for bone lengthening. However, the long treatment period and possible fibrous union or nonunion hampers its further clinical application. Bone regeneration in DO involves multiple stages of repair and coordinated action of multiple cell types. Consequently, it may be possible to enhance bone regeneration through treatment strategies that target more than one repair process or cell types. The goal of this study was to determine the combined effects of recombinant human bone morephogenetic protein 2 (rhBMP-2) and NEL-like molecule-1 (NELL-1) on bone formation in DO. Unilateral tibiae in 48 rabbits were lengthened for 7 days at a rate of 2 mm/day after 3-day lag. At the end of distraction, the animals were randomly divided into four groups ( n = 12) and received phosphate-buffered saline, 50 μg rhNell-1 or 50 μg rhBMP-2, or both 25 μg rhBMP-2 and 25 μg rhNell-1 at the lengthened segment, respectively. After 4-week consolidation bony healing was assessed using histology, radiography, dual energy X-ray absorptiometry, micro-CT, and three-point bend testing. Treatment with rhNell-1 and/or rhBMP-2 resulted in better bone formation and higher BMD and BMC than the saline group, whilst excellent bone formation and the highest BMD and BMC was observed in the combined treatment group. Both rhNell-1 and rhBMP-2 groups presented more mature characteristics in the micro-architecture than the saline group, whereas the combined treatment group presented the highest BV/TV, Tb.Th and Tb.N as well as the lowest Tb.Sp. The peak load of the lengthened tibia increased by 71% in the combined treatment group, 54% in the rhBMP-2 group, and 25% in the rhNell-1 group compared to the control group, respectively. This work suggests that BMP-2 and Nell-1 enhance each other's ability and dual delivery of two agents can significantly improve bony healing in tibial DO.

Elderly men with diabetes sustain hip fractures at higher BMD. Mr Os Sweden

Elderly men with diabetes sustain hip fractures at higher BMD. Mr Os Sweden

COL1 C-propeptide cleavage site mutations cause high bone mass osteogenesis imperfecta

Osteogenesis imperfecta (OI) is most often caused by mutations in the type I procollagen genes (COL1A1/COL1A2). We identified two children with substitutions in the type I procollagen C-propeptide cleavage site, which disrupt a unique processing step in collagen maturation and define a novel phenotype within OI. The patients have mild OI caused by mutations in COL1A1 (Patient 1: p.Asp1219Asn) or COL1A2 (Patient 2: p.Ala1119Thr), respectively. Patient 1 L1-L4 DXA Z-score was +3.9 and pQCT vBMD was+3.1; Patient 2 had L1-L4 DXA Z-score of 0.0 and pQCT vBMD of -1.8. Patient BMD contrasts with radiographic osteopenia and histomorphometry without osteosclerosis. Mutant procollagen processing is impaired in pericellular and in vitro assays. Patient dermal collagen fibrils have irregular borders. Incorporation of pC-collagen into matrix leads to increased bone mineralization. FTIR imaging confirms elevated mineral/matrix ratios in both patients, along with increased collagen maturation in trabecular bone, compared to normal or OI controls. Bone mineralization density distribution revealed a marked shift toward increased mineralization density for both patients. Patient 1 has areas of higher and lower bone mineralization than controls; Patient 2's bone matrix has a mineral content exceeding even classical OI bone. These patients define a new phenotype of high BMD OI and demonstrate that procollagen C-propeptide cleavage is crucial to normal bone mineralization.

The evidence for antiresorptive osteoporosis treatment in the elderly and old

Purpose The mean age at diagnosis of osteoporosis is in the late 1960s, and fracture risk and need for fracture prevention rises sharply with increasing age. However, what is the evidence that supports the use of antiresorptive osteoporosis treatments in elderly people? Methods This study was a meta-analysis and meta-regression of the published literature on the clinical efficacy of antiresorptive therapy in the reduction of fracture risk in elderly (age > 70 years) and old (age > 80 years). A systematic literature search was performed. Studies included were randomised placebo controlled trials of post-menopausal women or men where the primary endpoint was vertebral, non-vertebral or hip fracture risk reduction. No papers on fractures in males were published, so BMD as primary endpoint was accepted. Results Thirteen studies in women were included. We found increasing vertebral fracture risk reduction with increasing age, increasing BMI, and longer duration of treatment. A high baseline BMD was associated with a lesser effect. For non-vertebral fracture risk reduction, we found no effect of follow-up, age or BMD. For hip fracture risk reduction, we found no effect of treatment with increasing age or BMD, and no certain effect of duration of treatment. For men, three BMD studies were included, in these, we found a non-significant trend toward fracture reduction. Conclusions For women, pooled analyses showed increasing effect of antiresorptive drugs with increasing age, increasing BMI, and longer duration of treatment on vertebral fractures. The data on non-vertebral or hip fractures showed no effect on follow-up, age, or BMD. The data in men are scant at all sites and inconclusive.

The Relationships Between Current and Past Physical Activity Participation and Low BMD in a Mixed Menopausal Population

The Relationships Between Current and Past Physical Activity Participation and Low BMD in a Mixed Menopausal Population

Relatively High Bone Mineral Density in Chinese Adolescent Dancers Despite Lower Energy Intake and Menstrual Disorder

The effect of dietary restriction, intense exercise and menstrual dysfunction on bone mineral density remains controversial. The aim of this study was to assess the skeletal health status and relationship between bone mineral density and nutrient intake, menstrual status, estrogen level and other factos in Chinese adolescent dancers. Sixty dancers and 77 healthy controls underwent measurements of bone density, body composition, and estrogen level. Nutrient intake, menstrual status and physical activity were assessed with questionnaires. The correlation between these factors were analyzed. The dancers under study had a significantly lean body mass index (18.3 +/- 1.4 kg/m2 vs. 21.7 +/- 3.1 kg/m2), lower percentage of body fat (0.25 +/- 0.05 vs. 0.34 +/- 0.04) and later age at menarche (14.0 +/- 0.9 y vs. 13.0 +/- 1.3 y), and the estrogen level, daily calorie and fat intake in them were also lower than in the controls. All the dancers undertook intensive physical activity every day and up to 69% of them suffered from irregular menarche. Yet they had relatively high BMD and BMC of the total body and legs than the controls after adjusting for BMI and age. Site-specific BMD was positively correlated to BMI, body composition and training hours per week and negatively correlated to the age at menarche and menstrual frequency. The relatively high BMD and BMC of the dancers at the total body and legs were probably caused by high levels of weight-bearing physical activity. To ameliorate disordered eating, especially low energy intake might be helpful to prevent the Triad and to improve the bone health in adolescent dancers.

Higher habitual sodium intake is not detrimental for bones in older women with adequate calcium intake

Based on the calciuric effect of sodium (Na), it has been speculated, although not proven, that higher Na intake might have a detrimental effect on bone health. The objective was to determine the relationship between Na intake (expressed as urinary Na) and bone mineral density/content (BMD/BMC) during a 3-year study. Participants were healthy, postmenopausal, Caucasian women (n = 136 at baseline) with no medications affecting bone. After baseline screening, half were instructed to reduce sodium intake to approximately 1,500 mg/day (intervention). The other half remained on habitual intake of approximately 3,000 mg/day (control). All subjects were given calcium and vitamin D supplements to achieve recommended levels. Anthropometries, densitometry, blood and 24-h urine analyses, and dietary and activity records were assessed every 6 months. Data were analyzed as a continuum, irrespective of the initial assignment to a control or intervention group, using random effects regressions with repeated measures analysis of variance to examine changes over time. Results showed that subjects with higher Na intake had higher BMD in the forearm and spine at baseline and all subsequent time-points (p < 0.01). In the forearm, time and higher urinary calcium modified results, producing a curvilinear decrease in BMD (p < 0.01). In the spine, more active individuals had higher BMD at all time-points. We conclude that higher sodium intake, within the range consumed, had a positive effect on some skeletal sites and no adverse effect on bone in women who had adequate calcium and vitamin D intake.

New Variants in the Enpp1 and Ptpn6 Genes Cause Low BMD, Crystal-Related Arthropathy, and Vascular Calcification

A large genome-wide, recessive, N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen was performed on a mixed C57BL/6J and C3H.SW-H2/SnJ mouse background to identify genes regulating bone mass. Approximately 6500 male and female G(3) hybrid mice were phenotyped at 8 and 10 wk of age by DXA analysis for evidence of changes in unadjusted or body weight-adjusted BMD or BMC. Phenodeviant lines were identified based on statistical criteria that included a false discovery rate (FDR) <20% and Z-score >2.8. Genome-wide mapping scans were initiated on 22 lines, with evidence of high or low BMD or BMC that deviated by approximately -30% to +50% from the means. Several lines were discontinued as showing lack of heritability, but two heritable lines were identified with narrow chromosomal regions that allowed sequencing of potential mutant candidate genes. Novel mutations were identified in the Enpp1 (C397S) gene on chromosome 10 (line 4482) and the Ptpn6 (I482F) gene on chromosome 6 (line 4489) that were both associated with low bone mass. In addition, the phenotype of the Enpp1 mice showed a striking joint disease and calcification of blood vessels including the aorta, myocardium, and renal arteries and capillaries. These results support a role for the Enpp1 gene in the pathogenesis associated with mineralization of articular cartilage and vascular calcification. This work confirms the utility of the chemical mutagenesis approach for identification of potential disease genes and confirms the role of Enpp1 and Ptpn6 in regulating mineralization and skeletal bone mass.

Genome-Wide Haplotype Association Mapping in Mice Identifies a Genetic Variant in CER1 Associated With BMD and Fracture in Southern Chinese Women

BMD is a heritable trait and risk indicator for osteoporosis. In this study, we used a genome-wide haplotype association mapping (HAM) approach to identify a haplotype block within Cer1 that partitions inbred mice strains into high and low BMD groups. A cohort of 1083 high and low BMD human subjects were studied, and a nonsynonymous SNP (rs3747532) in human CER1 was identified to be associated with increased risk of both low BMD in premenopausal women (OR: 2.2; 95% CI: 1.0-4.6; p < 0.05) and increased risk of vertebral fractures (OR: 1.82, p = 0.025) in the postmenopausal cohort. We also showed that Cer1 is expressed in mouse bone and growth plate by RT-PCR, immunohistochemistry, and in situ hybridization, consistent with polymorphisms potentially influencing BMD. Our successful identification of an association with CER1 in humans together with our mouse study suggests that CER1 may play a role in the development of bone or its metabolism. Our study highlights the use of publicly available databases for rapidly surveying the genome for quantitative trait loci.

Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U.S. adults.

A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, whereas vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] status in regard to hip BMD, 4958 community-dwelling women and 5003 men >/=20 yr of age from the U.S. NHANES III population-based survey were studied. Calcium supplement users and individuals with a prior radius or hip fracture were excluded. We calculated standardized means for BMD by quartiles of sex-specific calcium intake for three 25(OH)D categories (<50, 50-74, and 75+ nM) among men and women, separately controlling for other important predictors of BMD. A higher calcium intake was significantly associated with higher BMD (p value for trend: p = 0.005) only for women with 25(OH)D status <50 nM, whereas calcium intake beyond the upper end of the lowest quartile (>566 mg/d) was not significantly associated with BMD at 25(OH)D concentrations >50 nM. Among men, there was no significant association between a higher calcium intake beyond the upper end of the lowest quartile (626 mg/d) and BMD within all 25(OH)D categories. Among both sexes, BMD increased stepwise and significantly with higher 25(OH)D concentrations (<50, 50-74, 75+ nM; p value for trend: women < 0.0001; men = 0.0001). Among men and women, 25(OH)D status seems to be the dominant predictor of BMD relative to calcium intake. Only women with 25(OH)D concentrations <50 nM seem to benefit from a higher calcium intake.