Johnson et al. (1997) described a family with very high spinal bone mineral density, the so-called spinal Z(BMD). In this kindred, the spinal Z(BMD) was 5.54 in 12 affected individuals and 0.41 in 16 unaffected individuals. The affected ... Johnson et al. (1997) described a family with very high spinal bone mineral density, the so-called spinal Z(BMD). In this kindred, the spinal Z(BMD) was 5.54 in 12 affected individuals and 0.41 in 16 unaffected individuals. The affected individuals had a normal skeletal structure and no other unusual clinical findings. In an accompanying editorial to the report of Johnson et al. (1997), Whyte (1997) noted that high bone mass can result from osteosclerosis and/or hyperostosis occurring focally or throughout the skeleton. Whyte (1997) pointed out that the term osteosclerosis refers to increased density of trabecular (spongy) bone, whereas hyperostosis refers to thickening of cortical (compact) bone from deposition of osseous tissue along subperiosteal and/or endosteal surfaces. According to Whyte (1997), there are at least 20 well-recognized, although rare, genetic causes of increased skeletal mass.
In a family with high bone mass linked to chromosome 11q13 (Johnson et al., 1997), Little et al. (2002) identified a mutation in the LRP5 gene (603506.0013). Boyden et al. (2002) identified the same mutation in affected members ... In a family with high bone mass linked to chromosome 11q13 (Johnson et al., 1997), Little et al. (2002) identified a mutation in the LRP5 gene (603506.0013). Boyden et al. (2002) identified the same mutation in affected members of a family with an autosomal dominant syndrome characterized by high bone mass, wide and deep mandible, and torus palatinus. Mizuguchi et al. (2004) performed an association study between bone mineral density and 9 candidate genes in 481 healthy Japanese women. They found that only LRP5 showed a significant association with BMD. A follow-up case-control study of 126 women with osteoporosis (see 166710) and 131 normal controls revealed a significant difference in allelic frequency of the LRP5 2220C-T SNP (603506.0019) (p = 0.009). The authors suggested that LRP5 is a BMD determinant and contributes to a risk of osteoporosis.
BMD and fracture rates vary among women of differing ethnicities. Most reports had suggested that BMD is highest in African Americans, lowest in Asians, and intermediate in Caucasians, yet Asians have lower fracture rates than Caucasians. Finkelstein et ... BMD and fracture rates vary among women of differing ethnicities. Most reports had suggested that BMD is highest in African Americans, lowest in Asians, and intermediate in Caucasians, yet Asians have lower fracture rates than Caucasians. Finkelstein et al. (2002) assessed lumbar spine and femoral neck BMD by dual-energy x-ray absorptiometry in 2,277 (for the lumbar spine) and 2,330 (for the femoral neck) premenopausal or early perimenopausal women participating in the Study of Women's Health Across the Nation (SWAN). BMDs were compared among ethnic groups before and after adjustment for covariates. Before adjustment, lumbar spine and femoral neck BMDs were highest in African American women, next highest in Caucasian women, and lowest in Chinese and Japanese women. Unadjusted lumbar spine and femoral neck BMDs were 7 to 12% and 14 to 24% higher, respectively, in African American women than in Caucasians, Japanese, or Chinese women. After adjustment, lumbar spine and femoral neck BMD remained highest in African American women, and there were no significant differences between the remaining groups. When BMD was assessed in a subset of women weighing less than 70 kg and then adjusted for covariates, lumbar spine BMD became similar in African American, Chinese, and Japanese women and was lowest in Caucasian women. Finkelstein et al. (2002) concluded that femoral neck BMD is highest in African Americans and similar in Chinese, Japanese, and Caucasians. They also suggested that these findings may explain why Caucasian women have higher fracture rates than African Americans and Asians.