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 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.

Trial registration: ClinicalTrials.gov NCT01440803.

Keywords: bone biopsy; bone turnover markers; premenopausal osteoporosis; teriparatide.

Published by Oxford University Press on behalf of the Endocrine Society 2020.

Figures

Figure 1.

Participant disposition. * Women allocated to teriparatide-first completed 24 months of teripataride at the 24-month visit. ** Women allocated to placebo-first completed 24 months of teriparatide at the 30-month visit. Withdrawn by investigator: 1 patient was removed after the 12-month visit and 2 patients were removed after the 18-month visit because they met predefined bone loss stopping criteria of >5% at any site and 1 patient was removed after the 18-month visit because of worsening nephrolithiasis.

Figure 2.

Six-month placebo-controlled trial of teriparatide versus placebo. A.) Lumbar spine (LS) BMD; B.) Total hip (TH) BMD; C.) Femoral neck (FN) BMD; D.) Serum P1NP; E.) Serum osteocalcin (OCN); F.) Serum C-telopeptide (CTX); G.) Cancellous bone formation rate (Cn-BFR); H.) Endocortical BFR (Ec-BFR); and I.) Intracortical BFR (Ic-BFR). Placebo: Black bars; Teriparatide: Gray bars. * P < 0.05 for between-groups comparison.

Figure 3.

Effect of 24 months of teriparatide expressed as percent change from baseline (± SE) on A.) BMD of the lumbar spine (LS), total hip (TH), femoral neck (FN), and distal radius (DR); B.) Trabecular bone score (TBS); and C.) Serum bone turnover markers: osteocalcin (OCN), P1NP, C-telopeptide (CTx). * P < 0.05 vs baseline.