Regional and hormone-dependent effects of apolipoprotein E genotype on changes in bone mineral in perimenopausal women

We studied 479 perimenopausal Danish women aged 45-58 years to examine diff erences between APOE genotypes with respect to (1) baseline total body bone mineral density (BMD) and densities measured in five different regions (ul tradistal forearm, proximal forearm, lumbar spine, femoral neck, and total hip region); (2) serum levels of alkaline phosphatase, bone isoenzyme alkal ine phosphatase, osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D, and urine hydroxyproline/creatinine excretion ratio; and (3) changes in bone mineral during 5 years of follow-up. Baseline BMDs were identical, whe reas serum levels of alkaline phosphatase and its bone isoenzyme were highe r in women with APOE 2-2 and APOE 2-3 than in women with APOE 3-3 and APOE 3-4 and lower in women with APOE 4-4. Among women not receiving hormonal-re placement therapy (HRT; n = 262), those with APOE 2-2 and APOE 2-3 had 30-4 0% lower rates of femoral neck and total hip bone mineral loss than women w ith APOE 3-3 and APOE 3-4, whereas the rates of mineral loss in other skele tal regions did not differ between these APOE genotypes. Women with APOE 4- 4 appeared to have lower rates of bone mineral loss in all regions. Women t reated with hormones throughout the follow-up period (n = 113) gained bone mineral, and women with APOE 3-4 and APOE 4-4 gained relatively more minera l than other women. A comparison of untreated and treated women with APOE 2 -3, APOE 3-3, and APOE 3-4 suggests a possible modification of the effect o f APOE genotype by HRT. In conclusion, the common APOE polymorphism has a c omplex effect on bone metabolism in perimenopausal Danish women including p ossible modification by hormone use: (1) among women not receiving HRT, tho se with APOE*2 have lower bone mineral losses in the femoral neck and hip r egion than other women, and (2) among women receiving HRT, those with APOE* 4 gain more bone mineral than other women.