Low bone mineral density (BMD) is a major risk factor for development of osteoporosis; increasing evidence suggests that attainment and maintenance of peak bone mass as well as bone turnover and bone loss have strong genetic determinants. We examined the association of BMD levels and their change over a 3-year period, and polymorphisms of the estrogen receptor (ER), vitamin D receptor (VDR), type I collagen, osteonectin, osteopontin, and osteocalcin genes in pre-and perimenopausal women who were part of the Michigan Bone Health Study, a population-based longitudinal study of BMD. Body composition measurements, reproductive hormone profiles, bone-related serum protein measurements, and life-style characteristics were also available on each woman. Based on evaluation of women, ER genotypes (identified by PvuII [n ‫؍‬ 253] and XbaI [n ‫؍‬ 248]) were significantly predictive of both lumbar spine (p < 0.05) and total body BMD level, but not their change over the 3-year period examined. The VDR BsmI restriction fragment length polymorphism was not associated with baseline BMD, change in BMD over time, or any of the bone-related serum and body composition measurements in the 372 women in whom it was evaluated. Likewise, none of the other polymorphic markers was associated with BMD measurements. However, we identified a significant gene ؋ gene interaction effect (p < 0.05) for the VDR locus and PvuII (p < 0.005) and XbaI (p < 0.05) polymorphisms, which impacted BMD levels. Women who had the (-/-) PvuII ER and bb VDR genotype combination had a very high average BMD, while individuals with the (-/-) PvuII ER and BB VDR genotype had significantly lower BMD levels. This contrast was not explained by differences in serum levels of osteocalcin, parathyroid hormone, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D. These data suggest that genetic variation at the ER locus, singly and in relation to the vitamin D receptor gene, influences attainment and maintenance of peak bone mass in younger women, which in turn may render some individuals more susceptible to osteoporosis than others. (J Bone Miner Res 1998;13:695-705)

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Objective. To determine whether Caucasian women ages 28-48 years with newly defined osteoarthri-tis (OA) would have greater bone mineral density (BMD) and less bone turnover over time than would women without OA. Methods. Data were derived from the longitudinal Michigan Bone Health Study. Period prevalence and 3-year incidence of OA were based on radiographs of the dominant hand and both knees, scored with the Kellgren/Lawrence (K/L) scale. OA scores were related to BMD, which was measured by dual-energy x-ray absorptiometry, and to serum osteocalcin levels, which were measured by radioimmunoassay. Results. The period prevalence of OA (K/L grade >2 in the knees or the dominant hand) was 15.3% (92 of 601), with 8.7% for the knees and 6.7% for the hand. The 3-year incidence of knee OA was 1.9% (9 of 482) and of hand OA was 3.3% (16 of 482). Women with incident knee OA had greater average BMD (z-scores 0.3-0.8 higher for the 3 BMD sites) than women without knee OA (P < 0.04 at the femoral neck). Women with incident knee OA had less change in their average BMD z-scores over the 3-year study period. Average BMD z-scores for women with prevalent knee OA were greater (0.4-0.7 higher) than for women without knee OA (P < 0.002 at all sites). There was no difference in average BMD z-scores or their change in women with and without hand OA. Average serum osteocalcin levels were lower in incident cases of hand OA (>60%; P 0.02) or knee OA (20%; P not significant). The average change in absolute serum osteocalcin levels was not as great in women with incident hand OA or knee OA as in women without OA (P < 0.02 and P < 0.05, respectively). Conclusion. Women with radiographically defined knee OA have greater BMD than do women without knee OA and are less likely to lose that higher level of BMD. There was less bone turnover among women with hand OA and/or knee OA. These findings suggest that bone-forming cells might show a differential response in OA of the hand and knee, and may suggest a different pathogenesis of hand OA and knee OA. Osteoarthritis (OA) is a major chronic disease. It has been estimated to affect 1 in 10 people at age 50 and 1 in 2 people at age 75 (1). Likewise, osteoporosis (OP) is a highly prevalent condition that has been estimated to affect 1 woman in 5 by age 80 (2). Thus, OP and OA are both common conditions that are more likely to affect women than men. It is relatively unusual, however, to find both conditions in the same individual. Early clinical comparisons showed that elderly persons undergoing resection of the femoral head to treat hip OA were much less likely to have evidence of bone loss than were elderly persons who had femoral neck fractures (3). Subsequent studies indicated that persons with OA of the knee or hip were more likely to have higher bone mass than normal subjects or subjects with OP (4-6), whereas patients with OA of the hand might not have greater bone mass (7-9). This suggests either a difference in the pathogenesis of hand and knee OA or a possible measurement artifact. (Great...

Mechanical stress on the cartilage and metabolic and/or hormonal influences have been suggested as possible etiologic factors for osteoarthritis. This paper reports findings from data collected in 1992 that were used to examine associations between osteoarthritis and risk factors in 573 Caucasian women aged 24-45 years from the Michigan Bone Health Study. Radiographs of the dominant hand and both knees were evaluated using the Kellgren and Lawrence grading scale. The prevalence of osteoarthritis (grade 2 or higher) in this population was 2.8% for hands and 3.6% for knees. Using polytomous multiple logistic regression, the authors found older age, increasing bone mineral density, and decreasing testosterone levels to be significantly associated with increasing hand scores. Older age and hand injury were significantly associated with grades of 2 or higher. Increasing osteoarthritis knee scores were associated with older age, increasing bone density, increasing body mass index, and current use of hormone replacement therapy. A knee grade of 2 or higher was associated with increasing estradiol levels, knee injury, and higher blood pressure. This study indicates that age, bone density, and injury are risk factors common to the development of hand and knee osteoarthritis in this non-elderly female population.