Characterization of Perimenopausal Bone Loss: a Prospective Study

This study characterized the change in bone mass, bone markers, pituitary/gonadal hormones, vitamin D, parathyroid hormone, and anthropometric variables in a cohort of healthy women as they passed through normal menopause. We recruited 75 women > 46 years old who had premenopausal estradiol (E2) and gonadotropin levels and regular menses. During 9.5 years of observation, 54 experienced normal menopause (PM group) and 21 remained estrogen replete (ER group). Before the beginning of the menopausal drop and after its completion, the slope of bone mass on time in the PM group was 0% for the spine, -0.61% per year for the total body, and -0.45 % per year for the femoral neck. Designating these losses as "age related," there were 0, 4.88, and 3.40% losses for spine, total body bone mineral (TBBM), and femoral neck, respectively, in the 8-year period for which the data were analyzed. Across menopause, we found a sigmoid pattern of bone loss in the PM group beginning about 2-3 years before the last menses and ending about 3-4 years after the last menses. The total estrogen-deprivation bone losses were 10.50, 7.73, and 5.30% for the spine, TBBM, and femoral neck, respectively. In the ER group, we found a 0, 0.59, and 0.93% per year loss in spine, TBBM, and femoral neck, respectively. Serum osteocalcin rose 77%, serum total alkaline phosphatase rose 34%, and urinary hydroxyproline/creatinine (Hypro/Cr) ratio rose 44% in the PM group, while remaining stable in the ER group. We conclude that menopausal bone loss is a composite of loss caused by estrogen deprivation and age per se for the hip and total body, but is caused by estrogen deprivation alone for the spine.