Combined parathyroid hormone (PTH) and bisphosphonate (alendronate—ALN) therapy has recently been shown to increase bone volume fraction and plate-like trabecular structure beyond either monotherapy. To identify the mechanism through which plate-like structure was enhanced, we used in vivo microcomputed tomography (μCT) of the proximal tibia metaphysis and individual trabecular dynamics (ITD) analysis to quantify connectivity repair (incidences of rod connection and plate perforation filling) and deterioration (incidences of rod disconnection and plate perforation). Three-month-old female, intact rats were scanned before and after a 12 day treatment period of vehicle (Veh, n = 5), ALN (n = 6), PTH (n = 6), and combined (PTH+ALN, n = 6) therapy. Additionally, we used computational simulation and finite element (FE) analysis to delineate the contributions of connectivity repair or trabecular thickening to trabecular bone stiffness. Our results showed that the combined therapy group had greater connectivity repair (5.8 ± 0.5% connected rods and 2.0 ± 0.3% filled plates) beyond that of the Veh group, resulting in the greatest net gain in connectivity. For all treatment groups, increases in bone volume due to thickening (5–31%) were far greater than those due to connectivity repair (2–3%). Newly formed bone contributing only to trabecular thickening caused a 10%, 41%, and 69% increase in stiffness in the ALN, PTH, and PTH+ALN groups, respectively. Moreover, newly formed bone that led to connectivity repair resulted in an additional improvement in stiffness, with the highest in PTH+ALN (by an additional 12%), which was significantly greater than either PTH (5.6%) or ALN (4.5%). An efficiency ratio was calculated as the mean percent increase in stiffness divided by mean percent increase in BV for either thickening or connectivity repair in each treatment. For all treatments, the efficiency ratio of connectivity repair (ALN: 2.9; PTH: 3.4; PTH+ALN: 4.4) was higher than that due to thickening (ALN: 2.0; PTH: 1.7; PTH+ALN: 2.2), suggesting connectivity repair required less new bone formation to induce larger gains in stiffness. We conclude that through rod connection and plate perforation filling PTH+ALN combination therapy improved bone stiffness in a more efficient and effective manner than either monotherapy.
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January 2015
Research-Article
Enhanced Individual Trabecular Repair and Its Mechanical Implications in Parathyroid Hormone and Alendronate Treated Rat Tibial Bone Available to Purchase
Allison R. Altman,
Allison R. Altman
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
36th Street and Hamilton Walk,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall
,36th Street and Hamilton Walk,
Philadelphia
, PA 19104e-mail: [email protected]
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Chantal M. J. de Bakker,
Chantal M. J. de Bakker
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424 Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
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Wei-Ju Tseng,
Wei-Ju Tseng
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424 Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
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Abhishek Chandra,
Abhishek Chandra
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424 Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
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Ling Qin,
Ling Qin
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424A Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424A Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
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X. Sherry Liu
X. Sherry Liu
1
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
426C Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,426C Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
1Corresponding author.
Search for other works by this author on:
Allison R. Altman
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
36th Street and Hamilton Walk,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall
,36th Street and Hamilton Walk,
Philadelphia
, PA 19104e-mail: [email protected]
Chantal M. J. de Bakker
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424 Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
Wei-Ju Tseng
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424 Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
Abhishek Chandra
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424 Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424 Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
Ling Qin
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
424A Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,424A Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
X. Sherry Liu
McKay Orthopaedic Research Laboratory,
Department of Orthopaedic Surgery,
426C Stemmler Hall,
e-mail: [email protected]
Department of Orthopaedic Surgery,
University of Pennsylvania
,426C Stemmler Hall,
36th Street and Hamilton Walk
,Philadelphia
, PA 19104e-mail: [email protected]
1Corresponding author.
Manuscript received June 16, 2014; final manuscript received September 30, 2014; accepted manuscript posted October 16, 2014; published online December 10, 2014. Assoc. Editor: Ara Nazarian.
J Biomech Eng. Jan 2015, 137(1): 011004
Published Online: January 1, 2015
Article history
Received:
June 16, 2014
Revision Received:
September 30, 2014
Accepted:
October 16, 2014
Online:
December 10, 2014
Citation
Altman, A. R., de Bakker, C. M. J., Tseng, W., Chandra, A., Qin, L., and Sherry Liu, X. (January 1, 2015). "Enhanced Individual Trabecular Repair and Its Mechanical Implications in Parathyroid Hormone and Alendronate Treated Rat Tibial Bone." ASME. J Biomech Eng. January 2015; 137(1): 011004. https://doi.org/10.1115/1.4028823
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