The impact of subcutaneous oestradiol implants on biochemical markers of bone turnover and bone mineral density in postmenopausal women

Abstract

Objective To evaluate the anabolic effect of oestrogen on bone by comparing the response of markers of bone formation (and resorption) and bone mineral density (BMD) to subcutaneous oestradiol implants. Design One year double-blind placebo controlled randomised study.Setting Clinical research unit within a teaching hospital.Population Twenty-one hysterectomised postmenopausal women were randomised to 25 mg oestradiol implants at baseline and at six months or to have a sham procedure at baseline and six months. Methods BMD and quantitative ultrasound (QUS) were assessed at baseline and one year. Bone alkaline phosphatase (bone ALP), procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), free deoxypyridinoline (iFDPD), N-telopeptide of type I collagen (NTX), serum oestradiol and intact parathyroid hormone (PTH) were measured at baseline, 4, 8, 12 and 24 weeks. Main outcome measures Percentage change markers of bone turnover and PTH and change in oestradiol levels over first six months and percentage of changes in DXA and QUS over one year. Results PINP, bone ALP and OC increased by 28%, 7% and 9%, respectively ( P < 0.01) during the first four weeks of treatment and then decreased significantly. Lumbar spine (LS) and total hip (TH) BMD increased by 5.4% and 6.0% ( P < 0.001), respectively, and femoral neck (FN) BMD by 3.7% ( P < 0.05) during the first year of treatment compared with control subjects. The peak serum oestradiol level was achieved four weeks after implant insertion. Mean PTH levels increased significantly in subjects receiving subcutaneous oestradiol. Conclusion Subcutaneous oestrogen exerted an apparent anabolic effect on bone, which was initially reflected by an increase in bone formation markers and later by a large increase in BMD.

Use of Bone Turnover Markers in Clinical Osteoporosis Assessment in Women: Current Issues and Future Options

“…Table 1 [51–74] is a summary of the changes in the International Osteoporosis Foundation (IOF) recommended biomarker levels in studies of drugs approved for treatment of OP, as well as biomarker data from clinical studies of drugs in development in women.…”

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“…Via ER, E2 has manifold biological effects. Biological targets of E2 are, inter alia, blood vessel walls [4-8], blood platelets [9], bone [7,10-12], breast cancer cells [13], central nervous system [7,14,15], retinal pigment epithelium [16], synthesis of clotting factors [17]. …”