Differential effects of teriparatide and denosumab on intact PTH and bone formation indices

AVA osteoporosis study

David W. Dempster, Hua Zhou, Robert R. Recker, Jacques P. Brown, Christopher P. Recknor, E. Michael Lewiecki, Paul D. Miller, Sudhaker D. Rao, David L. Kendler, Robert Lindsay, John H. Krege, Jahangir Alam, Kathleen A. Taylor, Boris Janos, Valerie A. Ruff

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Context: Denosumab-induced PTH elevation may stimulate early bone formation. Objective: Our objective was to evaluate whether denosumab-induced changes of intact PTH (iPTH) result in early anabolic effects according to histomorphometry and bone turnover markers (BTMs) compared with teriparatide, an established anabolic agent. Design: This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. Setting: This study took both in both US and Canadian sites. Participants: Sixty-nine postmenopausal women with osteoporosis were included. Interventions: Teriparatide (20 μg/day) for 6 months and denosumab (60 mg once) were used in this study. Main Outcome Measure: Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface, histomorphometric indices in four bone envelopes, and BTM and iPTH at baseline, 1, 3, and 6 months was undertaken. Results: After denosumab, iPTH peaked at month 1 (P<.001), then declined, remaining above baseline through month 6 (P≤.01); after teriparatide, iPTH declined at all time points (P<.001). From baseline to month 3, cancellous mineralizing surface/bone surface increased with teriparatide and decreased with denosumab and at month 3, was higher with teriparatide. Similar results were observed in other bone envelopes. BTMs increased from baseline in teriparatide-treated subjects (procollagen type 1 N-terminal propeptide at month 1 and carboxyterminal cross-linking telopeptide of type 1 collagen at month 3); procollagen type 1 N-terminal propeptide and carboxyterminal cross-linking telopeptide of type 1 collagen decreased from baseline at all time points in denosumab-treated subjects. Conclusions: Denosumab treatment increased iPTH but inhibited bone formation indices. In contrast, teriparatide treatment decreased iPTH but stimulated bone formation indices. These findings are not consistent with the hypothesis of early indirect anabolic effect with denosumab.

Original languageEnglish (US)
Pages (from-to)1353-1363
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number4
DOIs
StatePublished - Apr 1 2016

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Teriparatide
Osteogenesis
Osteoporosis
Bone
Collagen Type I
Anabolic Agents
Bone and Bones
Bone Remodeling
Denosumab
Labels
Therapeutics
Biopsy
Outcome Assessment (Health Care)
Labeling

All Science Journal Classification (ASJC) codes

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

Cite this

Differential effects of teriparatide and denosumab on intact PTH and bone formation indices : AVA osteoporosis study. / Dempster, David W.; Zhou, Hua; Recker, Robert R.; Brown, Jacques P.; Recknor, Christopher P.; Lewiecki, E. Michael; Miller, Paul D.; Rao, Sudhaker D.; Kendler, David L.; Lindsay, Robert; Krege, John H.; Alam, Jahangir; Taylor, Kathleen A.; Janos, Boris; Ruff, Valerie A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 4, 01.04.2016, p. 1353-1363.

Research output: Contribution to journalArticle

Dempster, DW, Zhou, H, Recker, RR, Brown, JP, Recknor, CP, Lewiecki, EM, Miller, PD, Rao, SD, Kendler, DL, Lindsay, R, Krege, JH, Alam, J, Taylor, KA, Janos, B & Ruff, VA 2016, 'Differential effects of teriparatide and denosumab on intact PTH and bone formation indices: AVA osteoporosis study', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 4, pp. 1353-1363. https://doi.org/10.1210/jc.2015-4181
Dempster, David W. ; Zhou, Hua ; Recker, Robert R. ; Brown, Jacques P. ; Recknor, Christopher P. ; Lewiecki, E. Michael ; Miller, Paul D. ; Rao, Sudhaker D. ; Kendler, David L. ; Lindsay, Robert ; Krege, John H. ; Alam, Jahangir ; Taylor, Kathleen A. ; Janos, Boris ; Ruff, Valerie A. / Differential effects of teriparatide and denosumab on intact PTH and bone formation indices : AVA osteoporosis study. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 4. pp. 1353-1363.
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T2 - AVA osteoporosis study

AU - Dempster, David W.

AU - Zhou, Hua

AU - Recker, Robert R.

AU - Brown, Jacques P.

AU - Recknor, Christopher P.

AU - Lewiecki, E. Michael

AU - Miller, Paul D.

AU - Rao, Sudhaker D.

AU - Kendler, David L.

AU - Lindsay, Robert

AU - Krege, John H.

AU - Alam, Jahangir

AU - Taylor, Kathleen A.

AU - Janos, Boris

AU - Ruff, Valerie A.

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N2 - Context: Denosumab-induced PTH elevation may stimulate early bone formation. Objective: Our objective was to evaluate whether denosumab-induced changes of intact PTH (iPTH) result in early anabolic effects according to histomorphometry and bone turnover markers (BTMs) compared with teriparatide, an established anabolic agent. Design: This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. Setting: This study took both in both US and Canadian sites. Participants: Sixty-nine postmenopausal women with osteoporosis were included. Interventions: Teriparatide (20 μg/day) for 6 months and denosumab (60 mg once) were used in this study. Main Outcome Measure: Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface, histomorphometric indices in four bone envelopes, and BTM and iPTH at baseline, 1, 3, and 6 months was undertaken. Results: After denosumab, iPTH peaked at month 1 (P<.001), then declined, remaining above baseline through month 6 (P≤.01); after teriparatide, iPTH declined at all time points (P<.001). From baseline to month 3, cancellous mineralizing surface/bone surface increased with teriparatide and decreased with denosumab and at month 3, was higher with teriparatide. Similar results were observed in other bone envelopes. BTMs increased from baseline in teriparatide-treated subjects (procollagen type 1 N-terminal propeptide at month 1 and carboxyterminal cross-linking telopeptide of type 1 collagen at month 3); procollagen type 1 N-terminal propeptide and carboxyterminal cross-linking telopeptide of type 1 collagen decreased from baseline at all time points in denosumab-treated subjects. Conclusions: Denosumab treatment increased iPTH but inhibited bone formation indices. In contrast, teriparatide treatment decreased iPTH but stimulated bone formation indices. These findings are not consistent with the hypothesis of early indirect anabolic effect with denosumab.

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