The association between age and bone mineral density in men and women aged 55 years and over: The Rotterdam Study

Burger, Huibert; Daele, Paul L A van; Algra, D.; Ouweland, F. A. Van Den; Grobbee, Diederick E.; Hofman, Albert; Kuijk, C. van; Schütte, H; Jc, Birkenhäger; Pols, Huibert A. P.

doi:10.1016/s0169-6009(08)80203-6

Cited by 169 publications

(113 citation statements)

References 35 publications

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“…We did not find an association of serum TSH levels with lumbar spine BMD. This might be due to the fact that the BMD measurements of the lumbar spine are influenced by osteoarthritis and therefore cannot be accurately assessed (32). The mechanisms of TSH effects on bone metabolism have not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

Heemstra

Deure

Peeters

et al. 2008

European Journal of Endocrinology

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Objective: It has been proposed that TSH has thyroid hormone-independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for triiodothyronine (T 3 ), free thyroxine (FT 4 ), and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSH receptor (TSHR)-Asp727Glu polymorphism to these relationships. Design: We performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma. Methods: We measured BMD of the femoral neck and lumbar spine. FT 4 , T 3 , TSH, bone-specific alkaline phosphatase, procollagen type 1 aminoterminal propeptide levels, C-cross-linking terminal telopeptide of type I collagen, and urinary N-telopeptide of collagen cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay. Results: We found a significant, inverse correlation between serum TSH levels and indicators of bone turnover, which was independent of serum FT 4 and T 3 levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was, however, no longer significant after adjusting for body mass index. Conclusion: We conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed. European Journal of Endocrinology 159 69-76

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Section: Discussionmentioning

confidence: 99%

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

Heemstra

Deure

Peeters

et al. 2008

European Journal of Endocrinology

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“…Characteristics of the population (age, body mass index [BMI], and bone mineral density [BMD]) (25) were assessed at baseline. Of the 963 subjects whose radiographs were scored, 77 were excluded because of the absence of scoring of radiographs at some of the sites considered for ROA assessment.…”

Section: Methodsmentioning

confidence: 99%

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Meulenbelt

Seymour

Nieuwland

et al. 2004

Arthritis & Rheumatism

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Objective. To study the role of the interleukin-1␤ gene (IL1B) and the IL-1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine.Methods. The study population consisted of a random sample of 886 subjects (ages 55-65 years) from a population-based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and ؊511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent.Results. Associations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele ؊511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0-3.4 and OR 2.9, 95% CI 1.4-6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1-3.4 and OR 3.3, 95% CI 1.4-7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear-by-linear association (P ‫؍‬ 0.00022). Conclusion.Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.Osteoarthritis (OA) is a joint disease characterized by degeneration of articular cartilage and remodeling of the subchondral bone with sclerosis. It has been demonstrated that genetic factors also play an important role in late-onset OA. Familial aggregation of OA (especially hand, knee, and hip OA) was observed in population-based studies (1-4). Candidate genes that may exert this genetic influence have been investigated by means of population-based association studies and genetic linkage studies in OA families. A large number of association studies using various definitions of OA have been performed, mainly investigating genes encoding structural proteins of the extracellular matrix of cartilage (e.g., COL2A1, CRTM, and AGN) or genes playing a role in the regulation of bone density and mass (e.g., VDR, IGF1, and ER), and have shown both positive and negative results for each of the genes (for review, see ref. 5). These differences in study results may indicate either false-positive or false-negative results, could be the result of differences in the OA phenotype investigated, or could be attributable to different linkage disequilibrium (LD) between the associated polymorphism and the causal mutation in various populations. Moreover, it is becoming increasingly clear that the genetic risk factors for OA at different joint sites may be distinct (6).Several groups of investigators have performed genome-wide screens of sibling pairs or nuclear families with OA and reported multiple chromosome areas (e.g., 2p24, 3p12, 4q32, 11q12, 4q27, Xp11.3, and 7p22) that show positive linkage to specific OA phenotypes, such as radiographic OA (ROA) in the distal interphalangeal (DIP) joints, s...

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“…For 544 of the 846 subjects (64%) measurements of the joint space were available. Bone density (grams/square centimeter) at the femoral neck was measured by dual energy x-ray absorptiometry as described previously (17).…”

Section: Methodsmentioning

confidence: 99%

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Uitterlinden¹,

Burger²,

Huang³

et al. 1997

J. Clin. Invest.

139

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Osteoporosis and osteoarthritis are age-related disorders of the skeleton with genetic components. Low bone density is a risk factor for osteoporotic fracture while osteoarthritis is associated with increased bone density. The 1,25-dihydroxyvitamin D 3 receptor (VDR) gene locus was previously found to be associated with bone density. We therefore studied the relationship between radiographic osteoarthritis at the knee and VDR genotype in a population-based sample ( n ϭ 846), using molecular haplotyping of anonymous intragenic DNA polymorphisms. Radiographic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN). We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustment for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density. The association appeared to be largely explained by the presence of osteophytes rather than JSN. Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association. ( J. Clin. Invest. 1997. 100:259-263.)

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The association between age and bone mineral density in men and women aged 55 years and over: The Rotterdam Study

Cited by 169 publications

References 35 publications

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

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