Abstract
Context: Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling. Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL). Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study. Setting: The study was conducted at 12 U.S. and Canadian centers. Subjects: Healthy postmenopausal women with osteoporosis participated in the study. Interventions: Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35). Main Outcome Measures: The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured. Results: Among 58 subjects with evaluable biopsies (TPTD=28; ZOL=30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P <0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P <0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points. Conclusions: TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.
| Original language | English |
|---|---|
| Pages (from-to) | 2799-2808 |
| Number of pages | 10 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 97 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2012 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Clinical Biochemistry
- Endocrinology
- Biochemistry, medical
- Endocrinology, Diabetes and Metabolism
Cite this
Skeletal histomorphometry in subjects on teriparatide or zoledronic acid therapy (SHOTZ) study : A randomized controlled 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, D. Sudhaker; Miller, Paul D.; Woodson, Grattan C.; Lindsay, Robert; Binkley, Neil; Wan, Xiaohai; Ruff, Valerie A.; Janos, Boris; Taylor, Kathleen A.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 8, 08.2012, p. 2799-2808.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Skeletal histomorphometry in subjects on teriparatide or zoledronic acid therapy (SHOTZ) study
T2 - A randomized controlled trial
AU - Dempster, David W.
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, D. Sudhaker
AU - Miller, Paul D.
AU - Woodson, Grattan C.
AU - Lindsay, Robert
AU - Binkley, Neil
AU - Wan, Xiaohai
AU - Ruff, Valerie A.
AU - Janos, Boris
AU - Taylor, Kathleen A.
PY - 2012/8
Y1 - 2012/8
N2 - Context: Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling. Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL). Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study. Setting: The study was conducted at 12 U.S. and Canadian centers. Subjects: Healthy postmenopausal women with osteoporosis participated in the study. Interventions: Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35). Main Outcome Measures: The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured. Results: Among 58 subjects with evaluable biopsies (TPTD=28; ZOL=30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P <0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P <0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points. Conclusions: TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.
AB - Context: Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling. Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL). Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study. Setting: The study was conducted at 12 U.S. and Canadian centers. Subjects: Healthy postmenopausal women with osteoporosis participated in the study. Interventions: Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35). Main Outcome Measures: The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured. Results: Among 58 subjects with evaluable biopsies (TPTD=28; ZOL=30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P <0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P <0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points. Conclusions: TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.
UR - http://www.scopus.com/inward/record.url?scp=84864796286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864796286&partnerID=8YFLogxK
U2 - 10.1210/jc.2012-1262
DO - 10.1210/jc.2012-1262
M3 - Article
C2 - 22701017
AN - SCOPUS:84864796286
VL - 97
SP - 2799
EP - 2808
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 8
ER -