A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial

David W. Dempster, Hua Zhou, Robert R. Recker, Jacques P. Brown, Michael A. Bolognese, Christopher P. Recknor, David L. Kendler, E. Michael Lewiecki, David A. Hanley, Sudhaker D. Rao, Paul D. Miller, Grattan C. Woodson, Robert Lindsay, Neil Binkley, Jahangir Alam, Valerie A. Ruff, Eileen R. Gallagher, Kathleen A. Taylor

Research output: Contribution to journalArticle

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Abstract

Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all four bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months.

Original languageEnglish
Pages (from-to)1429-1439
Number of pages11
JournalJournal of Bone and Mineral Research
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2016

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zoledronic acid
Teriparatide
Osteoporosis
Longitudinal Studies
Bone and Bones
Osteogenesis
Biopsy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial. / Dempster, David W.; Zhou, Hua; Recker, Robert R.; Brown, Jacques P.; Bolognese, Michael A.; Recknor, Christopher P.; Kendler, David L.; Lewiecki, E. Michael; Hanley, David A.; Rao, Sudhaker D.; Miller, Paul D.; Woodson, Grattan C.; Lindsay, Robert; Binkley, Neil; Alam, Jahangir; Ruff, Valerie A.; Gallagher, Eileen R.; Taylor, Kathleen A.

In: Journal of Bone and Mineral Research, Vol. 31, No. 7, 01.07.2016, p. 1429-1439.

Research output: Contribution to journalArticle

Dempster, DW, Zhou, H, Recker, RR, Brown, JP, Bolognese, MA, Recknor, CP, Kendler, DL, Lewiecki, EM, Hanley, DA, Rao, SD, Miller, PD, Woodson, GC, Lindsay, R, Binkley, N, Alam, J, Ruff, VA, Gallagher, ER & Taylor, KA 2016, 'A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial', Journal of Bone and Mineral Research, vol. 31, no. 7, pp. 1429-1439. https://doi.org/10.1002/jbmr.2804
Dempster, David W. ; Zhou, Hua ; Recker, Robert R. ; Brown, Jacques P. ; Bolognese, Michael A. ; Recknor, Christopher P. ; Kendler, David L. ; Lewiecki, E. Michael ; Hanley, David A. ; Rao, Sudhaker D. ; Miller, Paul D. ; Woodson, Grattan C. ; Lindsay, Robert ; Binkley, Neil ; Alam, Jahangir ; Ruff, Valerie A. ; Gallagher, Eileen R. ; Taylor, Kathleen A. / A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial. In: Journal of Bone and Mineral Research. 2016 ; Vol. 31, No. 7. pp. 1429-1439.
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abstract = "Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all four bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months.",
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AU - Zhou, Hua

AU - Recker, Robert R.

AU - Brown, Jacques P.

AU - Bolognese, Michael A.

AU - Recknor, Christopher P.

AU - Kendler, David L.

AU - Lewiecki, E. Michael

AU - Hanley, David A.

AU - Rao, Sudhaker D.

AU - Miller, Paul D.

AU - Woodson, Grattan C.

AU - Lindsay, Robert

AU - Binkley, Neil

AU - Alam, Jahangir

AU - Ruff, Valerie A.

AU - Gallagher, Eileen R.

AU - Taylor, Kathleen A.

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N2 - Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 μg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all four bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months.

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