Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee.

OBJECTIVE: Although knee malalignment is assumed to correlate with knee osteoarthritis (OA), it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA. The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA. METHODS: A total of 1,501 participants in the Rotterdam study were randomly selected. Knee OA at baseline and at followup (mean followup 6.6 years) was scored according to the Kellgren/Lawrence (K/L) grading system. Alignment was measured by the femorotibial angle on radiographs at baseline. Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA. RESULTS: Of 2,664 knees, 1,012 (38%) were considered to have normal alignment, 693 (26%) had varus alignment, and 959 (36%) had valgus alignment. A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 0.97-2.44), and varus alignment was associated with a 2-fold increased risk (OR 2.06, 95% CI 1.28-3.32). Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non-overweight persons. The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment (OR 2.90, 95% CI 1.07-7.88). CONCLUSION: An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA. However, this association seems particularly applicable to overweight and obese persons.

Body mass index associated with onset and progression of osteoarthritis of the knee but not of the hip: the Rotterdam Study.

OBJECTIVE: To investigate the relationship between body mass index (BMI) and the incidence and progression of radiological knee as well as of radiological hip osteoarthritis. DESIGN: Cohort study. SETTING: Population based. PARTICIPANTS: 3585 people aged > or =55 years were selected from the Rotterdam Study, on the basis of the availability of radiographs of baseline and follow-up. MAIN OUTCOME MEASURES: Incidence of knee or hip osteoarthritis was defined as minimally grade 2 at follow-up and grade 0 or 1 at baseline. The progression of osteoarthritis was defined as a decrease in joint space width. METHODS: x Rays of the knee and hip at baseline and follow-up (mean follow-up of 6.6 years) were evaluated. BMI was measured at baseline. RESULTS: A high BMI (>27 kg/m(2)) at baseline was associated with incident knee osteoarthritis (odds ratio (OR) 3.3), but not with incident hip osteoarthritis. A high BMI was also associated with progression of knee osteoarthritis (OR 3.2). For the hip, a significant association between progression of osteoarthritis and BMI was not found. CONCLUSION: On the basis of these results, we conclude that BMI is associated with the incidence and progression of knee osteoarthritis. Furthermore, it seems that BMI is not associated with the incidence and progression of hip osteoarthritis.

Bone mineral density and vertebral fracture history are associated with incident and progressive radiographic knee osteoarthritis in elderly men and women: the Rotterdam Study.

OBJECTIVE: To study the association between baseline femoral neck and lumbar spine bone mineral density (BMD), prevalent fractures and incident and progressive radiographic osteoarthritis (ROA) of the knee in men and women. METHODS: A sample of 1403 subjects (829 women and 574 men) was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. Incidence and progression of ROA in quartiles of femoral neck (FN) and lumbar spine (LS) BMD were determined using the Kellgren score, and separate analyses were made for men and women. Furthermore, incidence and progression of ROA were compared in subjects with and without a prevalent vertebral or non-vertebral fracture at baseline. RESULTS: The incidence of knee ROA of subject in the highest FN BMD (10.5%) and LS BMD (14.3%) was significantly higher than of those in the lowest quartiles (3.4% and 3.3% respectively), with corresponding adjusted odds ratios (95% confidence interval) of 2.8 (1.2-6.8) and 4.7 (2.1-10.7). The same trend was seen in the association between LS BMD and the progression of knee ROA, but no association was found between FN BMD and progression of ROA. Separate analyses for men and women both showed significant increased risks in the presence of high baseline BMD, with higher odds ratios in men than in women but larger confidence limits due to lower number of cases in men. Combined incidence and progression of knee ROA in subjects with a prevalent vertebral but not with a prevalent non-vertebral fracture at baseline was 8 times lower than subject without a fracture, independent of baseline BMD. CONCLUSIONS: High systemic BMD at baseline is associated with increased incidence and progression of knee ROA in both men and women, while a prevalent vertebral fracture has a protective effect.

Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk.

In view of the interactions of vitamin D and the estrogen endocrine system, we studied the combined influence of polymorphisms in the estrogen receptor (ER) alpha gene and the vitamin D receptor (VDR) gene on the susceptibility to osteoporotic vertebral fractures in 634 women aged 55 yr and older. Three VDR haplotypes (1, 2, and 3) of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms and three ERalpha haplotypes (1, 2, and 3) of the PvuII and XbaI restriction fragment length polymorphisms were identified. We captured 131 nonvertebral and 85 vertebral fracture cases during a mean follow-up period of 7 yr. ERalpha haplotype 1 was dose-dependently associated with increased vertebral fracture risk (P < 0.001) corresponding to an odds ratio of 1.9 [95% confidence interval (CI), 0.9-4.1] per copy of the risk allele. VDR haplotype 1 was overrepresented in vertebral fracture cases. There was a significant interaction (P = 0.01) between ERalpha haplotype 1 and VDR haplotype 1 in determining vertebral fracture risk. The association of ERalpha haplotype 1 with vertebral fracture risk was only present in homozygous carriers of VDR haplotype 1. The risk of fracture was 2.5 (95% CI, 0.6-9.9) for heterozygous and 10.3 (95% CI, 2.7-40) for homozygous carriers of ERalpha haplotype 1. These associations were independent of bone mineral density. In conclusion, interaction between ERalpha and VDR gene polymorphisms leads to increased risk of osteoporotic vertebral fractures in women, largely independent of bone mineral density.

Determination of the modulus of elasticity of bone material by an acoustical approach at the forearm distinguishes women with and without vertebral fractures independent of bone mineral density.

The modulus of elasticity is a parameter characterizing fracture stability of bone independent of bone mineral density. Measurement of acoustical properties of the forearm by determination of the resonant frequency of the ulna in longitudinal direction as a function of sound transmission velocity after adjustment of the measuring result by ulna length yields information about the modulus of elasticity. It was the aim of this study to investigate whether this parameter may distinguish between subjects with and without vertebral fractures independent of bone mineral density. Fifty females (61.1 +/- 9.1 years) were enrolled into the study, 25 with, and 25 age-matched without prevalent osteoporotic vertebral fracture(s). Especially low bone mineral density was not considered an exclusion criteria for enrollment into the control group. Resonant frequency of the ulna multiplied by ulna length was significantly lower in the group with prevalent fractures (53.6 +/- 6.8 m/s versus 56.8 +/- 5.2 m/s) after adjustment for age and after additional adjustment for forearm bone mineral density. Linear regression analysis showed complete independence of the acoustical parameter from bone mineral density. This study demonstrates that the modulus of elasticity of bone material is an independent risk factor for osteoporotic fractures. Acoustical measurement at the forearm by analyzing the resonant frequency of the ulna and correcting it by ulna length as geometrical parameter is capable of determining the modulus of elasticity in vivo.

The collagen Ia1 SP1 polymorphism is associated with differences in ultrasound transmission velocity in the calcaneus in postmenopausal women.

Bone mineral density (BMD) and fracture risk are under genetic control. An association of a G to T polymorphism in the Sp1 binding site of the collagen Ia1 (COLIa1) gene with the risk for fractures has been previously reported. This association is only partly explained by differences in BMD. Thus, we analyzed the relationship between the COLIa1 Sp1 polymorphism and ultrasound (US) transmission velocity (speed of sound; SOS) in bone. In a population-based sample of 740 women (aged 55-80 years) we determined COLIa1 genotype and US parameters in the calcaneus. SOS in the "GG" genotype group was 1522 +/- 31 m/sec, in the "GT" group, 1519 +/- 30 m/sec, and in the "TT" group 1508 +/- 30 m/sec (P = 0.01). While the difference between the GG and TT genotype groups corresponds to 0.5 SD or 1%, we observed an allele-dose-effect of 4.3 m/sec decrease in SOS per each copy of the "T" allele (P = 0.01). The differences remained significant after adjustment for BMD measured at the femoral neck. When we analysed 45 incident nonvertebral fractures in this group of women, we found the risk for fracture by COLIA1 Sp1 genotype to be partly explained by SOS differences as well as by BMD differences. Linear regression analysis showed a progressive negative slope of the regression line of SOS over age from "GG" over "GT" to "TT" genotype. These data indicate that the collagen Ia1 Sp1 polymorphism is associated with the modulus of elasticity of bone as determined in vivo by acoustical measurement. The relationship is independent of BMD and increases with age, contributing to an explanation of the increased fracture risk observed for this polymorphism.