Effect of Teriparatide on Bone Remodeling and Density in Premenopausal Idiopathic Osteoporosis: A Phase II Trial.
Abstract
CONTEXT Premenopausal women with idiopathic osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). OBJECTIVES Compare 6 months (M) of teriparatide versus placebo on areal bone mineral densit...
CONTEXT Premenopausal women with idiopathic osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). OBJECTIVES Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. DESIGN 6M phase 2 randomized controlled trial (RCT) followed by open extension. SETTING Tertiary referral centers. PATIENTS Premenopausal women with IOP. INTERVENTIONS A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. MAIN OUTCOME MEASURES 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. FINDINGS Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: -0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. CONCLUSIONS Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.