Effect of teriparatide on bone remodeling and density in premenopausal idiopathic osteoporosis: A phase II trial

Adi Cohen, Stephanie Shiau, Nandini Nair, Robert R. Recker, Joan M. Lappe, David W. Dempster, Thomas L. Nickolas, Hua Zhou, Sanchita Agarwal, Mafo Kamanda-Kosseh, Mariana Bucovsky, John M. Williams, Donald J. McMahon, Julie Stubby, Elizabeth Shane

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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. (J Clin Endocrinol Metab 105: 1–17, 2020)

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume105
Issue number10
DOIs
StatePublished - Oct 1 2020

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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