Hormone replacement therapy (HRT) using estrogen is FDA-approved in the US to prevent postmenopausal osteoporosis; however, the effects of combining HRT with drugs such as teriparatide are unclear.OBJECTIVE
To test the additive effects of teriparatide in preventing (or reversing) BMD loss in postmenopausal women taking HRT.DESIGN AND INTERVENTION
In this multinational, double-blind, placebo-controlled, parallel, randomized study, 247 postmenopausal women (aged 30-85 years) were included. All had been postmenopausal for at least 5 years and all had osteoporosis or low bone mass (T score at least −1). At enrollment, 122 of the women had been taking HRT for at least 12 months; the remainder were HRT-naive. All participants took HRT during the study: they either continued their treatment or started HRT, with regimes chosen by their physician or else provided by the study sponsor. Participants were randomly allocated to receive placebo or teriparatide (40 μg/day); the dose of 20 μg/day that is currently used in the clinic was approved only after this trial started. Of those on placebo, 48.8% of women had previously been taking HRT, whereas 50.0% of those on teriparatide had previously been taking HRT. All women took supplemental calcium and vitamin D.OUTCOME MEASURES
BMD was measured using dual-energy X-ray absorptiometry at the lumbar spine (at baseline, 3, 6, and 12 months, and study end), and at the hip, femoral neck, whole body and radius (at baseline, 12 months, and at study end). Serum levels of bone-specific alkaline phosphatase (BSALP) were measured at baseline, 1, 3, 6, and 12 months, and study end.RESULTS
The study lasted a median of 13.8 months. Women who had previously been taking HRT showed smaller increases in BMD than those who started HRT for this study. BMD at the lumbar spine, hip, and femoral neck increased steadily, compared with baseline BMD in all groups; at endpoint the differences were significant (P<0.01). In women taking teriparatide and HRT, there was a significant increase in BMD at all timepoints at these sites, compared with women taking HRT alone (P<0.01). For example, lumbar spine BMD increased by 14.0%, compared with baseline, in women taking HRT and teriparatide, whereas the increase was 3.0% in women taking HRT alone. Among women taking teriparatide, there was an increase of 11.2% in BMD at the lumbar spine in those continuing HRT, compared with 16.9% in those starting HRT. Among adverse events, only nausea and leg cramps were significantly higher in women taking teriparatide, compared to those taking placebo (P<0.05). In the teriparatide groups, BSALP levels were significantly higher at all times compared with placebo (P<0.001); in women taking teriparatide, those starting HRT showed a steady increase in BSALP levels, whereas levels in women continuing HRT peaked after 1 month.CONCLUSION
Addition of teriparatide enhanced the increases in BMD resulting from HRT, especially in HRT-naive women.